Late-Breaking
Abstracts
1st International Societies for
Investigative Dermatology Meeting
10-13 May 2023
Tokyo, Japanwww.isid2023.org

Late-Breaking
ABSTRACTS
International Societies for Investigative Dermatology (ISID) 2023
May 10-13, 2023
Keio Plaza Hotel Tokyo, Tokyo, Japan
Late-Breaking Abstracts Table of Contents

PAGE
3-7

Adaptive and Auto-Immunity

Abstracts LB1630 - LB1646

8-9

Artificial Intelligence (AI) and Image Analysis

Abstracts LB1647 - LB1653

10-12

Carcinogenesis and Cancer Genetics

Abstracts LB1654 -LB1665

13-15

Cell-Cell Interactions in the Skin

Abstracts LB1666 - LB1676

16-20

Clinical Research - Epidemiology and Observational Research

Abstracts LB1677 - LB1696

21-23

Clinical Research - Interventional Research

Abstracts LB1697 - LB1706

24

Clinical Research – Socio-behavioral and Health Services Research

Abstracts LB1707 – LB1710

25-26

Epidermal Structure and Barrier Function

Abstracts LB1711 - LB1718

27-30

Genetic Disease, Gene Regulation, and Gene Therapy

Abstracts LB1719 - LB1731

31-33

Innate Immunity, Microbiology, and Microbiome

Abstracts LB1732 - LB1743

34-36

Pharmacology and Drug Development

Abstracts LB1744 - LB1754

37-39

Photobiology

Abstracts LB1755 - LB1763

40

Pigmentation and Melanoma

Abstracts LB1764 - LB1767

41-42

Skin of Color

Abstracts LB1768 - LB1772

43-45

Skin, Appendages, and Stem Cell Biology

Abstracts LB1773 - LB1783

46-48

Tissue Regeneration and Wound Healing

Abstracts LB1784 - LB1795

49-50

Translational Studies

Abstracts LB1796 - LB1801

51-55

Author Index

56

Keyword Index

Adaptive and Auto-Immunity

LB1630Modular analysis of the psoriasis transcriptome identifies biomarkers of clinicalresponse to distinct classes of biologics and elucidates drug and disease endotypes
across skin and blood
A. Rider1, G. Smith1, 3, D. Watson2, 3
1
Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom, 2King's
College London, London, United Kingdom, 3PSORT, Consortium, United Kingdom|

Late-Breaking ABSTRACTSLB1631

The association between anti-U1-RNP antibodies with clinical manifestations andmultiorgan damage in systemic sclerosis and systemic lupus erythematosus
L. H. Vu1, D. H. Le2, P. T. Hoang31
Laser Department, Benh vien Da lieu Trung uong, Hanoi, Hanoi, Viet Nam, 2Director,
Benh vien Da lieu Trung uong, Hanoi, Hanoi, Viet Nam, 3Outpatient department, Benhvien Da lieu Trung uong, Hanoi, Hanoi, Viet Nam

Abstract Body Biologics have transformed psoriasis treatment and improved
outcomes for many patients. However, clinical response to these drugs isheterogeneous and reproducible predictive biomarkers are lacking. We aimed to
identify gene expression changes induced by treatment with adalimumab (ADA;TNF inhibitor) and ustekinumab (UST; IL-12/23 inhibitor) and expression signaturesassociated with clinical response to these drugs. Bulk mRNA-Seq was performed on
lesional (LS) and non-lesional (NL) skin biopsies and blood derived from 83 psoriasis
patients (41 for each drug in skin; 40 ADA and 43 UST in blood) at baseline, week
1 and week 12 (718 total samples). Clinical response was defined as percentage
reduction in psoriasis area and severity index (PASI) at week 12 compared tobaseline. Weighted gene correlation network analysis (WGCNA) was applied to theskin and blood samples separately, identifying 34 co-expressed gene modules in skinand 26 in blood. The first principal component of each module was correlated withdemographics, PASI and clinical response. In LS skin, an oxidative phosphorylation
module exhibited ADA-specific downregulation at week 1 and a cell cycle module
exhibited UST-specific downregulation at week 1. The eigengenes of 9 modules atbaseline in LS skin were significantly (FDR <= 0.05) associated with clinical response
to ADA; there were 6 such modules associated with response to UST. Importantly,
these treatment and response-associated expression signatures were replicatedin an independent validation cohort. Module-PASI associations were widespread in
LS skin; strikingly, 17 modules in NL skin and 19 modules in blood were associatedwith PASI. In summary, our findings identify novel pathways modulated by biologic
treatment, identify the first replicable transcriptomic biomarkers of response indistinct tissue compartments, and highlight the effect of PASI on the NL skin andblood transcriptomes.

Abstract Body Objective: To evaluate the association between anti-U1-RNP antibodies
with clinical manifestations and multiorgan damage in systemic sclerosis (SSc) andsystemic lupus erythematosus (SLE). Method: A descriptive, cross-sectional study
on 55 SSc and 48 SLE Vietnamese patients from July 2021 to September 2022. The
serum anti-U1-RNP antibodies was analyzed using the immunoblot method. Result:
A total of 55 SSc and 48 SLE patients were eligible for this analysis, among which the
majority was female.. Anti-U1-RNP antibodies were present in 8 (14.5%) SSc patientsand 19 (39.6%) SLE patients, mainly positive at strong level 3+. In univariate analysis,
SSc patients positive for anti-U1-RNP antibodies had significantly higher prevalenceof skin thickness (mRodnan 27,3 ± 6,1 vs 20,2 ± 5,8), periungual vasodilatation (87.5%
vs 38.3%), periungual hemorrhage (37.5% vs 6.4%), pulmonary arterial hypertension
assessed by transthoracic echocardiography (85.7% vs 34.0%) than those negative foranti-U1RNP antibodies. Meanwhile, SLE patients positive for anti-U1-RNP antibodies
had also higher prevalence of Raynaud phenomenon (63.2% vs 17.2%), interstitiallung disease diagnosed by high-resolution thin-layer computed tomography (58.8%
vs 23.8%), FEV1<80% (64.3% vs 30.0%). Anti-U1-RNP antibodies in SSc and SLE
patients were confirmed to be independently associated with interstitial lung disease,pulmonary hypertension, muscle damage [odds ratio >1]. In addition, there was anegative association with subclinical anemia and proteinuria. Conclusion: In thiscohort of SSc and SLE patients, anti-U1-RNP antibodies were associated with several
clinical features such as skin thickness, lung, renal and hematologic disorders as wellas small vasculitis. Keywords: Systemic sclerosis, systemic lupus erythematosus,
anti-U1-RNP, clinical manifestations, multiorgan damage

LB1632

LB1633PD-1 signaling plays a critical role for inhibiting development of autoimmune
disease-associated dermatitis in childhood
K. Oya , Y. Nakamura , Z. Zhenji , N. Okiyama , T. Nomura , Y. Fujisawa
1
Dermatology, Tsukuba Daigaku, Tsukuba, Ibaraki, Japan, 2Dermatology, Tokyo Ika
Shika Daigaku, Bunkyo-ku, Tokyo, Japan, 3Dermatology, Ehime Daigaku, Matsuyama,
Ehime, Japan
1

1

1

2

1

3

Abstract Body Autoimmune diseases, such as lupus erythematosus anddermatomyositis, are caused by disruption of immune tolerance toward self-tissues
and are frequently associated with dermatitis. Autoimmune disease-associateddermatitis typically shows interface dermatitis, characterized by T cell infiltration
around the basal layer, causing keratinocyte apoptosis, which suggests that T cells
target keratinocyte self-antigens. Interestingly, prognosis and response to treatmentof such autoimmune diseases differ between pediatric and adult patients; however,
the mechanisms remain largely unknown. To address this, we generated doubletransgenic (DTg) mice by crossing K14-mOVA mice, in which ovalbumin (OVA) is
expressed on keratinocytes, with OT-I transgenic mice that have OVA-specific T cell
receptors. DTg mice developed dermatitis around the eyes after birth. Histologicalinvestigation revealed inflammatory cell infiltration around the basal layer andkeratinocyte apoptosis, suggesting that DTg mice mimic dermatitis associated withhuman autoimmune diseases. CD8+ T cells in the spleen of DTg mice expressedhigher levels of PD-1 than controls; however, when PD-1 expression was compared
between DTg mice of different ages, 2-week-old mice showed higher PD-1 expression
compared with 8-week-old mice. While the administration of anti-PD-1 antibody
exacerbated dermatitis in 2-week-old DTg mice, no exacerbation was observedin 8-week-old mice. Thus, our findings indicate that PD-1 signaling is critical for
inhibiting autoimmune disease-associated dermatitis development at a younger age.

Some autoantibodies in overlap syndrome of connective tissue diseases
P. T. Hoang1, L. H. Vu2, D. H. Le3
1
Outpatient Department, Benh vien Da lieu Trung uong, Hanoi, Hanoi, Viet Nam, 2Laser
Department, Benh vien Da lieu Trung uong, Hanoi, Hanoi, Viet Nam, 3Director, Benh vien
Da lieu Trung uong, Hanoi, Hanoi, Viet Nam

Abstract Body The study was performed on 63 Overlap syndrome patients at NHDV
from July 2019 to August 2020. Aim: to evaluate incident of some autoantibodies inoverlap syndrome of connective tissue diseases. Result: 84,5% of the patients was
female, the most common Overlap type is SSc/SLE (39,7%) and SSc/DM. ANA is themost prevalent autoantibody (98,4%), then anti RNP/Sm (42,9%), anti Ro-52 (42,9%),anti Ku (27%) and anti PM/Scl (11,1%). As for the autoantibodies detected in clinicalvariants of Overlap syndrome, anti SSA (32%), anti Ro-52 (56%) and anti RNP/Sm aremostly found in SSc/SLE; anti Ku (45,5%) and anti PM/Scl-75 (18.,2%) in SLE/DM; andanti Scl-70 (31,8%) and anti PM/Scl-100 (13,6%) in SSc/DM.

3Adaptive and Auto-Immunity|

Late-Breaking ABSTRACTSLB1634

LB1635

S. D. Lytton1, C. Prodinger2, R. Maglie3, D. Meyersburg2, B. Mussnig2, E. Antiga3,
J. Bauer2
1
SeraDiaLogistics, Munich, Germany, 2SALK, Salzburg, Austria, 3DHS, Firenze, Italy

M. Neumann1, S. Gonther1, P. Schilf1, C. Sadik1, 2
Department of Dermatology, Allergy, and Venereology, Universitat zu Lubeck, Lubeck,
Schleswig-Holstein, Germany, 2Center for Research on Inflammation of the Skin (CRIS),
Universitat zu Lubeck, Lubeck, Schleswig-Holstein, Germany

Novel auto-antigen peptide epitopes as theranostic targets in incurable autoimmune
blistering diseases

Abstract Body Introduction: The major obstacle to develop innovative immune
therapies in rare bullous pemphigoid (BP) is the identification of continuous peptide
epitopes displaying high affinity binding to autoreactive B-cells receptors in thepatient’s blood. Using peptide-CAR T-cells, one can deliver more precise immune
modulation than Rituximab, which gives largely non-specific B-cell depletion andincomplete remission. Methods: Prospective serum samples of thirty-three BP
patients, 16 female 17 male, median age 85 years (range 64-90) having confirmed
direct immune fluorescence (DIF) IgG and/or complement C3 deposition clinicallyassociated with blisters, erosion and/or lesions on limbs and trunk were tested
in enzyme linked immunoassay (MBL ELISA BP180 IgG and BP230 IgG). Thirteen
serum with BP180 IgG >60 U/mL or BP230 IgG > 60 U/mL and two controls werescreened for reactivity in a 600 peptide array of 17mer peptides printed in duplicate
derived from overlapping sequences of NC16-BP180, BP180C-terminus and BP230
C-terminus and control viruses. Results: Positive BP180 IgG in 24 of 33 (73%) andpositive BP230 IgG in 19 of 33 (58%) BP patients gave ELISA reactivity with meanvalues of 56 U/mL (95% CI 39-74 U/mL) and mean 48 U/mL (95% CI 30-66 U/mL),
respectively. The peptide array fluorescent intensities reveal specific reactivity
against 13 continuous epitopes (nine BP180, four BP230). The autoantibody profile
of a larger BP cohort by ELISA, and binding of fluorescent peptides to patient CD19
B cells by flow cytometry are under evaluation. Conclusions: Preliminary findings
underscore the potential of BP180-BP230 peptide ELISA to have greater sensitivity
than the recombinant auto-antigen based commercial ELISA. Further studies on
BP180 and BP230 peptide epitopes which selectively target autoreactive B cells
in BP patients are warranted to develop novel therapeutics; CAR-T cells and automonoclonal antibodies (AutoMAbs).

LB1636

Safety, tolerability and pharmacokinetics of TPM203, a tolerizing topas particle
mixture in pemphigus vulgaris (PV): Preliminary results from a phase 1, first in man
study (TPV11)
D. Didona1, K. Volkmann1, J. Hinterseher1, C. Möbs1, R. Pollmann1, A. Polakova1,
W. Pfützner1, T. Cunha1, S. Fleischer2, M. Hertl1
1
Department of Dermatology and Allergology, Philipps-Universitat Marburg, Marburg,
Germany, 2Topas Therapeutics GmbH, Hamburg, Germany

Abstract Body PV is a severe autoimmune disorder of the mucous membranes
and skin, which is caused by IgG auto-antibodies against desmoglein (Dsg)3.
Pathogenesis depends on recognition of Dsg3 epitopes by autoreactive T cells, mainly
restricted by HLA-DRB1*04:02. We report on the single ascending dose part of TPV11phase 1 open label study, in which 12 patients (4 cohorts of 3 PV patients each) with
anti-Dsg3 IgG, no-to-moderate disease activity, and no immunosuppressives otherthan ≤10 mg/d of prednisone, received TPM203 at 0.12, 0.36, 1.2 and 3.6μmol of total
peptide and were followed-up for 12 weeks. TPM203 is a mixture of 4 different Topas
particle conjugates (TPC) each coupled to a distinct Dsg3 T cell epitope, shown to
induce tolerance against Dsg3 in an HLA-DRB1*0402-transgenic mouse model of PV.
Eleven patients reported at least one adverse event (AE), none of which was severeor serious. Three PV-related AEs were mild. Mild-to-moderate worsening of PV wasreported in 2 patients following COVID vaccination. No clinically relevant changes
in laboratory parameters were observed. Detectable TPC levels were only found at
the two highest doses. A trend towards decreased anti-Dsg3 IgG was found withthe first 3 dose levels. There was also a decrease in CD27+ memory B and Th17
cells in contrast to an increase in Th2, Tfh2 and Treg cells (all % change, 95% CI).
In 5/12 patients, a decrease of memory T cells and Th17, Th17.1 and Th1 cells was
associated with diminished anti-Dsg3 IgG. Thus, escalating single doses of TPM203
were safe and well-tolerated in the studied PV patients. Despite the small patientnumber and single drug administration, the preliminary data could indicate that thisT cell-targeted approach might modulate the immune response in PV patients byincreasing Treg and decreasing Th17 and memory B cells.

Metabolic intervention with 2-DG ameliorates symptoms in a model of atopic
dermatitis

1

Abstract Body Atopic Dermatitis (AD) is a chronic, Th2-type-mediated diseaseoften manifesting in infancy. Current treatment options are limited to topicalglucocorticoids and systemic immunosuppressants solely alleviating the detrimental
symptoms. These therapies fail to target disease-driving factors and innovative
treatment approaches are needed. Immune cell activation is coherent with cell
metabolism alterations, such as aerobic glycolysis and mitochondrial activity.
2-Deoxyglucose (2-DG) and oligomycin are known to efficiently inhibit aerobic
glycolysis and mitochondrial oxidation in diverse autoimmune diseases. Here, weinvestigated the effect of 2-DG and oligomycin on symptom severity in a model of
AD. C57BL/6J wild-type mice were randomly allocated into four treatment groups(Control (CTRL), 2-DG, oligomycin, and 2-DG+oligomycin) and AD-like symptoms
were induced with epicutaneous application of the vitamin D3-analogue Calcipotriol(MC903). Our results show that 2-DG- and 2-DG+oligomycin-, but not oligomycintreated mice, display significantly alleviated symptoms compared to the CTRL group.
Ear thickness in the 2-DG- (p=0.0001) and 2-DG+oligomycin-treated (p=0.0001) mice
was significantly reduced compared to the CTRL group. Histological evaluation
revealed a significant decrease of the epidermal (e) and dermal (d) thickness in
2-DG- (e: p=0.0015; d: p=0.0088) and 2-DG+oligomycin-treated mice (e: p=0.0026;
d: p=0.0021) compared to the CTRL mice. Whereas transepidermal water loss was
only significantly reduced in the 2-DG+oligomycin-treated compared to the CTRL
animals (p=0.0075). Lastly, no differences in immune cell population were detected
between the groups in different organs. Taken together, our results provide evidence
that inhibition of aerobic glycolysis results in significant symptom amelioration in amurine model of AD. We suggest that aerobic glycolysis plays a crucial role in thepathogenesis of AD and constitutes a promising novel therapeutic target.

LB1637

Maintenance and functional analysis of mast cells in atopic dermatitis-like skin
Y. H. Keith1, 2, T. Honda3, S. Ono1, B. Lee4, S. Nakamizo1, S. Hanakawa4, Y. Ishida1,
K. Kabashima1, 41
Dermatology, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Japan,
2
Precision Immunology Program, Garvan Institute of Medical Research, Darlinghurst,
New South Wales, Australia, 3Dermatology, Hamamatsu Ika Daigaku, Hamamatsu,
Shizuoka, Japan, 4Agency for Science Technology and Research, Singapore, Singapore

Abstract Body Atopic dermatitis (AD) is an inflammatory skin disease presenting
chronic pruritic eczema. A significant increase of mast cells (MCs) is commonly
observed in AD skin and their activation can affect the inflammation by evoking
pruritus and secreting various inflammatory mediators. Although skin MCs aremaintained locally by self-proliferation of skin-resident MCs in a steady state, how
they are maintained in AD remains unknown. In this study, we first revealed theinfiltration of bone marrow-derived circulating MC progenitors (MCps) in MC903induced AD-like skin using BM-chimera mice and parabiosis. We then demonstrated
that bone marrow-derived MCps differentiate into skin-type MCs at the late phaseof inflammation. Finally, we investigated the possible function of MCs in MC903induced AD skin, distinguishing between skin resident and BM-derived infiltrating
MCs. Ear swelling showed a tendency the decrease in skin-resident MC-deficient
mice (intradermal injection of diphtheria toxin to Mas-TRECK mice), and there was nodifference in ear swelling in BM-derived infiltrating MC-deficient mice (BM-chimeric
WT mice with KitWsh/Wsh mice-derived BM cell transplant). In conclusion, bone marrowderived MC progenitors infiltrate AD-like skin and generate functional MCs. Our study
provides a novel insight into MC heterogeneity and their functional difference invarious inflammatory skin diseases.

4Adaptive and Auto-Immunity

LB1638|Late-Breaking ABSTRACTSLB1639Methylation of PSMB9 is involved in determining prognosis and checkpoint
therapies in skin cutaneous melanoma via interferon-gamma pathway
X. Hu1, Z. Hu2, Q. Cheng2, H. Feng1
1
Hunan Provincial People's Hospital, Changsha, Hunan, China, 2Xiangya Hospital
Central South University, Changsha, Hunan, China

Peripheral resident M2 macrophages deficiency exacerbated inflammation in
imiquimod- induced psoriasis mouse model
H. Tsuda1, K. Watanabe1, A. Matsumoto1, M. Komine2, S. Iwamoto1
1
Human Genetics, Jichi Ika Daigaku, Shimotsuke, Tochigi, Japan, 2Dermatology,
Jichi Ika Daigaku, Shimotsuke, Tochigi, Japan

Abstract Body Skin cutaneous melanoma (SKCM) is the most malignant form of skincancer; despite advances in immunotherapy, poor response rates pose a challenge.
Attempts have been made to predict potential immunotherapy outcomes. DNA
methylation, a key player in epigenetic alterations and tumorigenesis, is a candidate
for predicting therapy response. Using machine-learning techniques, we showed thatmethylation of PSMB9 is a critical factor in SKCM development and is associated withpoor response to immune checkpoint blockade (ICB) therapy. By analyzing changes
in interferon-related genes at the methylation level in 472 melanoma samples, we
identified a distinct subtype with increased sensitivity to interferon-gamma (IFN-g).
Using various algorithms, we constructed a 10-probe model and established an IFN-g
high-sensitivity signature. To assess the methylation status of the IFN-response, wedeveloped an IFN methylation score (IMS), which was further validated by pan-cancer
analysis. To explore the contribution of PSMB9 to the signature, we overexpressed
PSMB9 to mimic the hypomethylated state and found that it inhibited melanoma cellproliferation and migration. Our results suggest that PSMB9 methylation is a criticalprognostic indicator and predictor of response to immunotherapy in melanoma
patients.

Abstract Body Psoriasis is one of major skin inflammatory diseases with various
comorbid diseases. Cytokines-targeted therapeutics, such as antibodies for TNFα, IL17A and IL-12/23 p40, or IL-23p19, and Janus kinase inhibitors were proven effective,
however complete cure of this disease has not been achieved. Increase in M1
macrophages and decrease in M2 macrophages have been reported in lesional skinof psoriasis. However, it is not clear whether the M1-skewed balance in macrophagesis the cause or result of psoriasis pathogenesis. We developed mice with peripheral
M2 macrophages deficiency knocking out Trib1 in myeloid lineage cells utilizing
LysM-cre mice, and investigated the role of M2 macrophages in the pathogenesis ofpsoriasis induced by imiquimod (IMQ) treatment in mice. M2 macrophages in Trib1flox/LysM-cre (Trib1 cKO) mice are deficient in chemotaxis and other functions.
Seven days after IMQ treatment, ear thickness of Trib1 cKO mice was significantly
thicker than that of wild type (WT) mice. Serum concentration of IL-17A and TNFα
was significantly increased after IMQ treatment, however there was no difference
between Trib1 cKO and WT mice. Gene expression analysis of IMQ-treated backskin by qPCR showed that expression of IL-17A and TNFα was not significantly
difference between Trib1 cKO and WT mice. Cxcl2, an activator of neutrophils andeosinophils, was increased in Trib1 cKO mice treated by IMQ compared to WT mice.
IMQ treatment increased Ly6C-positive and Ly6G-positive cells in splenocytes shownby flow cytometer, which were more increased in Trib1 cKO mice compared to WT
mice. These results suggested that peripheral resident M2 macrophage deficiency
increased risk of increment of neutrophils and monocyte cells, and exacerbate
inflammation induced by IMQ in mice.

LB1640

LB1641

Dynamic profiling of desmoglein 3-reactive T helper cells in pemphigus vulgaris
K. Volkmann1, 2, J. Hinterseher1, A. Polakova1, D. Didona1, M. Hertl1
1
Department of Dermatology and Allergology, Philipps-Universitat Marburg, Marburg,
Hessen, Germany, 2Bundesinstitut fur Arzneimittel und Medizinprodukte, Bonn,
Nordrhein-Westfalen, Germany

Abstract Body Pemphigus vulgaris (PV) is an autoimmune blistering disease of skinand mucous membranes and is associated with IgG against desmoglein (Dsg) 3. We
and others have shown that in PV T helper cells provide critical help to B cells foranti-Dsg3 IgG production. Here we introduce a novel, easy-to-perform ex vivo assay
aimed at detecting and characterizing disease-promoting Dsg3-reactive peripheral
blood T helper cells. CFSE-stained PBMC from 38 PV patients and 13 healthy controls(HC) were stimulated ex vivo with five immunodominant peptides residing in theextracellular domains (EC) 1, 2 and 3 of Dsg3. Proliferating Dsg3-reactive CD4+ T
helper cells were detected by FACS analysis and secreted cytokines were measured
in the culture supernatants. Overall, T cell recognition of all the five Dsg3 epitopes
was seen in active PV and to a lesser extent in remission, while PBMC from HC were
only stimulated by 3/5 Dsg3 peptides. In active disease, Th1, Th2 and Th17-related
cytokines were secreted by Dsg3-specific cells while Th2 cytokines outweighed overall
Th1 and Th17 cytokines in remission. However, there was a statistically significant
increase of the Th1 cytokines, IFN-γ and TNF-α and of the regulatory cytokine, IL-10,
in clinical remission. These findings support the concept of a Th17/ Th2-dominatedsignature in PV and the involvement of Treg cells in immune tolerance against Dsg3.
In summary, combined phenotypical and functional analyses presented here may
serve as the so far most sensitive T cellular parameters for immune intervention
studies in PV.

Short-term IL-23 neutralization reduces IL-23 transcription and number of activatedpro-inflammatory mononuclear phagocyte (MNPs) in psoriasis skin ex vivo
L. Zondler1, K. I. Pappelbaum1, J. Angsana2, J. Obeid3, K. Eyerich4, K. Schäkel5,
A. Tsianakas6, S. Malynn8, M. W. Leung2, S. Wegner7, M. Bertolini1
1
Monasterium Laboratory GmbH, Münster, Germany, 2Janssen R&D LLC, San Diego,
California, United States, 3Janssen, Issy-les-Moulineaux, France, 4University of Freiburg,
Freiburg, Germany, 5UniversitatsKlinikum Heidelberg, Heidelberg, Baden-Württemberg,
Germany, 6Fachklinik Bad Bentheim, Bad Bentheim, Germany, 7Janssen-Cilag, Neuss,
Germany, 8Janssen Sciences, Dublin, Ireland

Abstract Body In psoriasis, inflammatory signaling in the skin is primarily driven by
the interleukin (IL)-23/Th17 axis. Systemic blockade of IL-23 in psoriasis patientshas led to high levels of clinical response, accompanied by reduced frequencies ofpro-inflammatory CD11c+CD14brightCD64bright monocyte-like cells, the main producersof IL-23 within mononuclear phagocyte (MNP) infiltrates in psoriatic lesions. Yet,
how IL-23 blockade regulates MNPs remains unclear. To study this, we treatedfull-thickness human lesional and peri-lesional psoriatic skin with an anti-IL23p19
subunit mAb for up to 72h ex vivo. The psoriatic phenotype was maintained duringorgan culture, as confirmed by demonstrating significantly higher numbers of
CD3+IL-17A+, CD14+CD11c+, and CD14-CD11c+ cells in lesional versus peri-lesional
skin, and release of IL-17A, CCL20, IL-1β, and β-defensin-2 into the medium. RNAseq
analysis confirmed expression of the psoriatic transcriptomic signature in lesional
compared to peri-lesional skin; this was partially corrected by IL-23 blockade inlesional skin, as demonstrated by a trend towards down-regulation of select genes(e.g. IL17A, CCL20, IL1B, and IL36G). IL-23 blockade also led to a trend in reductionof IL-17A and significant reduction of the keratinocyte or myeloid cell-derived
cytokines CCL20 and IL-1β. Importantly, neutralization of IL-23 in lesional skinresulted in decreased mRNA expression of IL23A, FCGR1A (CD64), CD40 and CD80,
and reduction in the proportions of CD40+ and CD64+ cells among CD14-CD11c+ andCD14+CD11c+, but not CD14+CD11c- cells. In conclusion, short-term IL-23 blockade
affects inflammatory MNP activities in a psoriasis skin explant model.

5Adaptive and Auto-Immunity

LB1642

Inhibition of spleen tyrosine kinase signaling pathway ameliorates imiquimodinduced psoriasis mouse model
C. Li1, E. Liao2
1
Children’s Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan,
2
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan

Abstract Body Psoriasis is a chronic inflammatory skin disease with a strong genetic
predisposition and autoimmune pathogenic traits. Psoriasis is found throughout
the world, but the prevalence varies among different ethnic groups. The worldwide
prevalence is about 2%. Psoriasis was originally thought of as a disorder primarilyof epidermal keratinocytes. Spleen tyrosine kinase (SYK) signaling pathway wascorrelated with inflammatory responses and pathogenic T cell differentiation.
However, it is still unknown whether inhibition of SYK activation would lead to downregulation of psoriatic dermatitis. Therefore, the present study investigated theeffect of the SYK inhibitor on imiquimod- induced psoriasis mouse model and IL-17A
stimulated HaCaT cell. The results showed that R406, the SYK inhibitor, could inhibit
the expression of IL-6 and IL-8 in IL-17A stimulated HaCaT cells at the dose without
cytotoxicity. In in vivo results, R406 decreased symptoms of psoriasis, including
ear thickness, skin redness, and scaling. The pathology showed that immune cells
infiltration was significantly decreased in the R406 treatment group. The expressionof Th17 cells in splenocytes was significantly suppressed by R406. In conclusion,
R406 may be a promising therapeutic candidate for the treatment of psoriasis.

LB1644

Transcriptome analysis defines combinatory pathway activity in keratinocytes
necessary for split formation in pemphigus vulgaris
U. Radine1, I. Burmester1, S. Guo1, W. V. Hariton2, 3, S. Rahimi2, 3, C. M. Hammers1,
R. J. Ludwig1, E. J. Müller2, 3, J. E. Hundt1, H. Busch1
1
Lübeck Insitute of Experimental Dermatology, Universitat zu Lubeck, Lubeck,
Schleswig-Holstein, Germany, 2Department of Dermatology, Universitat Bern, Bern,
Switzerland, 3Department for BioMedical Research, Universitat Bern, Bern, Switzerland

Abstract Body Pemphigus vulgaris (PV) is a blistering autoimmune disease of theskin and mucous membranes, in which autoantibodies target desmoglein 1 and/or
3 (Dsg1/3). This disrupts cell-cell adhesion between epidermal keratinocytes andleads to blister formation. The PV pathogenesis is not detailed yet, so we focus on
the molecular regulation occurring shortly after autoantibody binding. Here, we study
the transcriptome responses after split formation in a human skin organ culture(HSOC) model under single-chain variable fragment (scFv) PX43 (directed against
Dsg1/3) stimulation. Bulk RNA is taken from full-thickness skin or microdissectedbasal keratinocytes. In both cases, transcriptome responses are highly correlated,confirming a significant involvement of keratinocytes and not fibroblasts in split
formation. The keratinocytes transcriptionally respond with strong activation of
NFκB, JAK-STAT, EGFR/MAPK, and TGFβ, as well as Interferon α/β signaling, withthe latter potentially activating apoptosis-related processes. Repression of split
formation through targeted inhibition of either p38 MAPK, VEGFR, PI3K, MEK, or NGF
receptor TRKA resulted in inhibitor-specific pathway (de-)activation. NFκB and JAKSTAT were strongly upregulated irrespective of the inhibitor and most likely constitutean unspecific stress response. Inhibition of p38 MAPK, TRKA, or VEGFR caused theactivation of upstream WNT signaling. MEK inhibition down-regulated the upstream
EGFR/MAPK pathways. PI3K signaling was negatively affected through PI3K, p38
MAPK, and VEGFR inhibition. In conclusion, the results hint at multiple pathways andpathway combinations necessary for PV cell detachment, which will help to define
clinically relevant molecules driving tissue remodeling during injury and shed light on
the pre-disease state of PV.

|

Late-Breaking ABSTRACTSLB1643Novel insights into vitiligo-like depigmentation under immune checkpoint inhibitors
in melanoma compared to classical vitiligo and healthy skin biopsies
M. M. Ameri, R. Ziadlou, A. White, N. Li, N. Hermann, R. Dummer, M. Brüggen
Dermatology, UniversitatsSpital Zurich, Zurich, Switzerland

Abstract Body Immune checkpoint inhibitor (ICI) treatment for metastasizedmelanoma is often associated with immune-related adverse events, one of them
being vitiligo-like depigmentation (VLD). Classical vitiligo is an autoimmune diseaseconsidered to result from a cytotoxic response of resident memory T-cells against
melanocytes. However, the pathomechanisms underlying the development of VLD
are poorly understood. In this study, we wanted to investigate and explore thecellular and molecular signatures of VLD and classical vitiligo to gain insights into
pathomechanistic features of the two diseases. We collected lesional and nonlesional skin biopsies from 8 VLD patients receiving ICI for metastasized melanoma
and 8 classical vitiligo patients. In addition, we collected 8 healthy control (HC) skinsamples. All tissue specimens were processed using spatial whole transcriptomicsof regions of T cell infiltration. Differential gene expression and enrichment analysis
revealed distinct molecular profiles of VLD, vitiligo and HC. In VLD, there was anoverexpression of genes associated with activation of the MHC class II protein
complex (the HLA class II alpha/beta chain, CD74), which is critical for antigen
presentation to CD4+ T lymphocytes. Comparative enrichment analysis between VLD
and vitiligo showed more significant activation of genes related to peptide antigen
processing and presentation by MHC I, as well as signs of B cell activation (e.g.,
CD81 and IGHG2/4) in vitiligo. On the other hand, genes related to epidermal cells
and keratinocytes differentiation/development (e.g., CDH3, FLG, IRF6, LIPM, KRT)
were significantly upregulated in VLD compared to vitiligo. In conclusion, our spatialtranscriptomics analyses so far show distinct expression of antigen presentationand T cell-related genes in VLD vs. vitiligo. We will further map antigen presenting
cells and T cell subtypes, to better understand the immune axis in VLD.

LB1645

IL-9 sensitizes human pathogenic Th2 cells to pro-inflammatory IL-18 signals in
atopic dermatitis
S. Schärli1, F. Luther1, O. Steck1, J. Thyssen2, N. Bertschi1, C. Schlapbach1
1
Department of Dermatology, Inselspital Universitatsspital Bern, Bern, Switzerland,
2
Department of Dermatology and Allergology, Gentofte Hospital, Hellerup, Hovedstaden,
Denmark

Abstract Body Background: Pathogenic CRTh2+ T helper 2 (pTh2) cells are crucial
contributors to the pathogenesis of atopic dermatitis (AD) by secreting high levels
of interleukin (IL-)13 and IL-22. Yet, the upstream regulators of pTh2 cells in AD skinremain incompletely understood. IL-18 is one such putative regulator and is linked to
AD pathogenesis by multiple lines of evidence raising intriguing questions regarding
its role in the activation of pTh2 cells in AD skin. Objective & Methods: We sought
to decipher the role of IL-18 in human Th2 responses in AD by analyzing pTh2 cells
from AD patients, as well as ex vivo skin explants of human healthy and lesional AD
skin. Results: We first investigated the signals that induce interleukin 18 receptor (IL18R) expression on Th2 cells. Of all the cytokines for which pTh2 cells express thereceptor, only IL-9 was able to induce high levels of IL-18R via a previously unknown
TYK2/JAK1-STAT1 signaling pathway. Consistently, IL-9R+/IL-18R+ pTh2 cells werestrongly increased in the peripheral blood of AD patients. Functionally, stimulation of
circulating pTh2 cells with IL-18 induced secretion of IL-13 and IL-22, an effect thatwas significantly enhanced by co-stimulation with IL-9. Mechanistically, IL-18 induces
rapid and strong activation of both NF-κB and AP-1 signaling in pTh2 cells. In humanskin explants from lesional AD skin, neutralization of IL-18 rapidly downregulated
both IL-13 and IL-22 secretion from pTh2 cells. Finally, IL-18 protein levels correlated
positively with IL13 expression in lesional skin of AD. Conclusion: Collectively, ourdata reveal a previously underappreciated role of IL-9 and IL-18 as positive regulatorsof Th2 cell responses in human AD. Further, we uncover a novel signaling cascade
downstream of the IL-9R on pTh2 cells involving TYK2 and STAT1. These findings
may guide future therapeutic approaches aiming at inhibiting aberrant activation of
pTh2 cells in human skin.

6Adaptive and Auto-Immunity|

Late-Breaking ABSTRACTSLB1646

Bullous pemphigoid patients are colonized with clonally related USA200 S. aureus
strains
K. N. Messingham1, S. Kilgore2, P. Schlievert2, J. A. Fairley1
1
Dermatology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States,
2
Microbiology & Immunology, University of Iowa, Iowa City, Iowa, United States

Abstract Body Bullous pemphigoid (BP) is an autoimmune blistering disease
mediated by autoantibodies targeting collagen XVII. Despite a defined autoantigen,the events leading to autoimmunity, and its persistence, remain unknown. However,there is evidence that exposure to environmental pathogens may play a role in a
growing number of autoimmune diseases. Recently, we reported that the lesionsof most (85%) BP patients were colonized by Staphylococcus. aureus, althoughnone of the patients exhibited clinical signs of infection. Additionally, there was anincreased prevalence of S. aureus in the nares and on the surface of unaffected skinof patients with BP, while controls were primarily colonized with coagulase negative
staphylococci (normal flora). Further, homogeneous expression of virulence genes
within the enterotoxin gene cluster (egc) suggested that BP patients are colonized
by a clonal group of S. aureus that is similar to USA200 (CC30) strain. In this study,
bacterial whole genome sequencing of the BP isolates was performed to assesssequence similarity and capacity to produce known S. aureus virulence factors. We
observed high DNA sequence similarity in 11/12 S. aureus isolates. The 11 S. aureus
strains were clonally related based on having other typical USA200 (CC30) clonal
properties: 1) the presence of the TSST-1 and enterotoxin gene cluster genes; 2)a mutation in the structural gene of the cytotoxin α-toxin; 3) ability to produce thecytotoxin β-toxin; and 4) belonging to accessory gene regulatory group 3. The USA200
group of S. aureus is widespread in both community and healthcare settings but it isunclear if colonization is a preceding factor or a consequence of BP. Further studies
are needed to understand to understand the role of S. aureus in the pathogenesis ofBP.

7

Artificial Intelligence (AI) and Image Analysis

LB1647

Precise diagnosis and therapeutic effect evaluation by dermoscopy and calcium
fluorescent white staining for tinea capitis and other hair fungal infection
Y. RanDermatology, Sichuan University West China Hospital, Chengdu, Sichuan, China

Abstract Body We have applied dermoscopy and calcium fluorescent white staining
to the early diagnosis and efficacy evaluation of fungal infection in hair of tinea capitis(TC), which is significant in promoting accurate diagnosis and treatment. Numerous
short, highly convoluted, coiled and twisted corkscrew hairs at the first visit, and,cigarette-ash-shaped hairs after antifungal therapy in tinea capitis were noticed
under dermoscopy. Bright-green fluorescence was observed under UV-dermoscopy.
Accumulated scales around hair roots, black dots, and barcode-like hairs presented
with horizontal white bands were observed by polarized dermoscopy. Overall, 20
patients with tinea capitis were included in this study. Microsporun canis (13, 65%)
was the most commonly identified dermatophyte. Sixteen dermoscopic findings were
evaluated, and perifollicular scaling was the most frequent feature (100%), followed bydiffuse scaling, red background, white sheath around proximal hair shaft, and comma
hair (75%, 60%, 45%, and 30%, respectively). Other features were seen in about ≤20%of the patients. Under UV-dermoscopy, Microsporun canis TC (13, 65%) presented
green fluorescence or white and green fluorescence, Nannizzia (Microsporum)
gypseum TC (1, 5%) presented yellow fluorescence, and Trichophyton violaceum(3, 15%) and Trichophyton interdigitale of TC (3, 15%) presented no fluorescence.
The calcium fluorescent white staining can detect the fungal spores and hyphae veryclearly and quickly, which is easy to operate and timely and accurately identifies thefungal infections by specific staining of the fungal cell wall. Thus, it can significantly
improve its positive rate. A combination of dermoscopy with an ordinary light source,
polarized light and UV-dermoscopy, calcium fluorescent white staining, transmission
and scanning electron microscopy, and fungal culture/molecular identification (ITSPCR sequencing) could finally make a precise diagnosis. Other fungal hair infections
in eyelashes, eyebrows, nose, pubic, and vellus hair were also noticed.

LB1649Automated facial acne lesion detecting and counting algorithm for acne severity
evaluation and its utility in assisting dermatologists
D. Kim1, 4, S. Sun3, S. Cho1, H. Kong2, 5, J. Lee1, J. Lee1, 4, D. Suh1, 4
1
Department of Dermatology, Seoul National University College of Medicine, Seoul,
Korea (the Republic of), 2Transdisciplinary Department of Medicine and Advanced
Technology, Seoul National University Hospital, Seoul, Korea (the Republic of),3
Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea (theRepublic of), 4Acne, Rosacea, Seborrheic Dermatitis and Hidradenitis Suppurativa
Research Laboratory, Seoul National University Hospital, Seoul, Korea (the Republic of),
5Department of Biomedical Engineering, Seoul National University College of Medicine,
Seoul, Korea (the Republic of)

Abstract Body Introduction: Although lesion counting is an evaluation methodthat effectively analyzes facial acne severity, its usage is limited due to difficult
implementation. Objectives: We aimed to develop and validate an automatedalgorithm that detects and counts acne lesions by type, and evaluate its clinicalapplicability as an assistance tool through a reader test. Methods: Total 20,699
lesions (closed and open comedones, papules, nodules/cysts, and pustules) weremanually labeled on 1,213 facial images of 398 facial acne photography sets (frontal
and both lateral views) acquired from 258 patients and used for training and validating
algorithms based on convolutional neural network for classifying five classes of acne
lesions or for binary classification into noninflammatory and inflammatory lesions.
Results: In the validation dataset, the highest mean average precision was 28.48 forthe binary classification algorithm. Pearson’s correlation of lesion counts between
algorithm and ground-truth was 0.72 (noninflammatory) and 0.90 (inflammatory),
respectively. In the reader test, eight readers (100.0%) detected and counted lesions
more accurately using the algorithm compared with the reader-alone evaluation.
Conclusion: Overall, our algorithm demonstrated clinically applicable performance indetecting and counting facial acne lesions by type and its utility as an assistance toolfor evaluating acne severity.

|

Late-Breaking ABSTRACTSLB1648Novel skin permeability prediction tool based on an explainable regression model
analysis using PaDel descriptor for plant-based drug development
A. Hernawan1, W. Rahmaniar2, A. L. Sunarwidhi3
1
Department of Informatics Engineering, Faculty of Engineering, Universitas Mataram,
Mataram, Indonesia, 2Biomedical Artificial Intelligence Research Unit, Institute of
Innovative Research, Tokyo Kogyo Daigaku, Meguro-ku, Japan, 3Department ofPharmacy, Faculty of Medicine, Universitas Mataram, Mataram, Indonesia

Abstract Body A prediction tool of compound’s skin permeability would be usefulin plant-based transdermal drug and cosmetic formulation development. Due tothe huge array of metabolites found in plants, it would be difficult to assess eachcompounds manually. In the last decade, state-of-the-art deep neural network (DNN)
has achieved high-accuracy prediction with the availability of large bioinformatics
datasets. However, the problem with this state-of-the-art model is the absence oftransparency and interpretability. Therefore, a new strategy is needed. Here, we
purpose a new approach to address this issue, which is an explainable regression
model analysis using PaDel descriptor. In this study, DNN was applied to estimate
skin permeability on 326 diverse compounds. Each compound was encoded using
PaDel descriptor with 307 substructure fingerprints, 166 molecular access systemfingerprints, and 1,444 physicochemical properties. Then the DNN interprets with an
Explainable AI (XAI) SHAP. The results showed that this tool was able to screen highnumber of compounds and predict its skin permeability property with an increasedtransparency of the regression model. This tool would be a useful approach forpreliminary stage of plant-derived natural drug and cosmetic development.

LB1650

Revolutionizing allergen avoidance counseling strategies: Evaluating the integration
and reliability of ChatGPT in contact dermatitis management
P. Phadungsaksawasdi
Dermatology, Chulabhorn International College of Medicine, Thammasat University,
Rangsit, Pathumthani, Thailand

Abstract Body Artificial intelligence (AI) has become increasingly powerful andintegrated into various fields. A recent breakthrough in AI Chatbot (ChatGPT)
demonstrates a paradigm shift in how we interact with complex and time-consuming
data management. This study aims to investigate the use of AI chatbot in dermatology
practices to determine the extent of its integration and reliability. A contact dermatitis
model is employed as a case study due to its data-intensive nature. In practice, upon
identifying the allergen causing a patient's contact dermatitis, the next step is allergenavoidance counseling. Complex allergen names and difficult-to-read product labels
often pose challenges for both patients and dermatologists in selecting appropriate
products. This study included allergens from an international standard patch test
containing 30 allergen groups and selected three common exposure sources foreach allergen group. We tasked ChatGPT with recommending five products fromeach group that could be used if a patient is allergic to specific allergens and different
exposure sources. We then manually checked the accuracy of each product's
labeling and components to determine if the recommendation was accurate. Outof the 450 product recommendations requested from ChatGPT, it provided 400
recommendations (88.9% of total requests). Among these, 267 products (66.8% ofrecommended products) were accurate, while 55 products (13.8%) were incorrect(containing the allergen the patient is allergic to). The components of 78 products(19.5%) were unknown, as the authors could not find the relevant components forthese products. This preliminary data showing that ChatGPT demonstrates promisingpotential for utilization in daily dermatological practice. However, developing effective
strategies for generating commands to task AI chatbots is vital for obtaining accurate
results. This study serves as an example of a use case in dermatology, with more use
cases likely to emerge in the near future.

8Artificial Intelligence (AI) and Image Analysis

LB1651

Identification of the inflection points of wrinkle manifestation based on a big data
study of 431,321 women in China
F. Wang1, 2, W. Sha1, S. Fu2, Z. Li2, J. Wu2, X. Fu2, S. Wang1
1
Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences,
Chinese Academy of Science, Shanghai, China, 2Xiamen Meitueve Technology CO., Ltd,
Xiamen, China, Shanghai, China

Abstract Body Human organs are thought to be aging at different rates, and suchphysiological aging, unlike chronicle aging, does not proceed at an even pace.
Inflection points of aging pattern have been reported in previous studies on variousorgans. Different skin aging signs (e.g. wrinkles) should also have their uniqueprogressing patterns, but studies with limited sample size could hardly capture theskin aging pattern in an accurate way, and the potential inflection points remain
unknown. Here we present an unprecedented large-scale population study of 431,321
women in China, by measuring four wrinkle related skin aging signs (i.e., wrinkle undereyes, wrinkle in forehead, crow's feet and lacrimal sulcus). Our results show that theoverall wrinkle score inflects at the age of 47, indicating that the progressing rate ofwrinkle severity increases before this age. Specifically, the severity of wrinkle undereyes, wrinkle in forehead, crow's feet and lacrimal sulcus inflects at the age of 40, 52,
52 and 44, respectively – suggesting different progressing rates of various wrinkle
signs. In conclusion, our big data study provides strong and unprecedented evidence
for inflection points of wrinkle manifestation, and underscores the importance of
precision cosmetic prevention of different skin aging signs.

|

Late-Breaking ABSTRACTS

LB1652

Images of the hand are comparable to those of the face for predicting chronologicalage via AI
A. Georgievskaya1, T. Tlyachev1, K. Kiselev1, G. Hillebrand2, 3, K. Chekanov1,
D. I. Danko1, A. Golodyayev1, G. Majmudar3
HautAI, Tallinn, Estonia, 2University of Cincinnati, Cincinnati, Ohio, United States,
Amway Corp, Ada, Michigan, United States

1
3

Abstract Body The prediction of a person’s chronological age (CA) from visible skinfeatures using artificial intelligence (AI) is now commonplace in computer vision.
Most often, this is accomplished by convolutional neural network (CNN) models
based on facial images as the biometric data. However, hands also hold telltale
signs of a person’s age, maybe even more telling than the face. To determine theutility of hand images in predicting CA, we developed two deep CNNs, one basedon standardized dorsal hand images (H) and another on frontal face images (F).
Subjects (n=1454) were Indian women, ages 20-80, across 3 geographic cohorts(Mumbai, New Delhi, and Bangalore). Given the wide variability in skin types, eachsubject’s individual typology angle (ITA), a measure of overall skin color tone, wasdetermined on both F and H. Images were randomized and 70% of F and 70% of H
were used to train the two CNNs. The remaining 30% of F and H were retained as thevalidation dataset. CNN validation showed mean average error (MAE) for predicting
CA using F vs. H of 4.1 and 4.7 years, respectively. Furthermore, CA predicted fromF was highly correlated with that predicted by H (r=0.96, p<0.0001). The CNNs forboth F and H were validated for dark and light skin color tones. Finally, by blurringor accentuating specific visible features on regions of the hand and face such as
wrinkles and spots, we identified those features that contributed more or less to
the CNN models. For the face, areas of the inner eye corner and areas around themouth were most important for age prediction, however with some age dependence.
For the hands, knuckle texture was a key driver for age prediction. In conclusion,
for AI estimates of CA, CNNs based on hand images are a viable alternative andcomparable to CNNs based on images of the face.

LB1653

Genome-wide scans identified genetic variants associated with lacrimal sulcus in
Han Chinese
F. Wang2, 1, Q. Qi2, Z. Li1, X. Fu1, S. Wang2
1
Xiamen Meitueve Technology CO., Ltdv, Xiamen, China, 2Shanghai Institute of Nutrition
and Health, University of Chinese Academy of Sciences, Chinese Academy of Science,
Shanghai, China

Abstract Body Lacrimal sulcus, a groove located on the upper lateral surface of theanterior part of the maxilla bone, is influenced by both environmental and genetic
factors. Previous studies of lacrimal sulcus were largely based on traditional image
analysis or human assessments. In this study, we developed a deep learning framework
to precisely assess lacrimal sulcus. The trait was derived in more than 10,000 Han
Chinese from three independent cohorts: Jidong cohort (N=4,288), Taizhou cohort(N=2,914) and National Survey of Physical Traits cohort (NSPT, N=3,091). Our resultshows that the score of lacrimal sulcus from deep learning framework and humanassessment are highly correlated (PCC=0.94, P<0.001), while our deep learning
method is more stable than human assessment (Cv: 2.68% vs. 4.29%). A genomewide scan in Jidong cohort identified variants at 9q21.13associated with lacrimalsulcus (P=1.45×10-8), which was successfully replicated in the independent cohort(P<0.05). Moreover, meta-analysis of all three cohorts not only further enhanced
the significance level of the 9q21.13 association (P=3.85×10-13), but also identified
another signal at 18q12.2(P=4.89×10-8). In conclusion, by utilizing deep learningbased measurement on lacrimal sulcus, our study successfully identified novel
genetic risk factors in Han Chinese.

9Carcinogenesis and Cancer Genetics

LB1654

Mitochondrial transfer from cancer cells induces pro-tumorigenic features in skinfibroblasts|

Late-Breaking ABSTRACTS

LB1655WITHDRAWN

M. Cangkrama, H. Liu, J. Whipman, C. Gaebelein, J. Vorholt, S. Werner
Eidgenossische Technische Hochschule Zurich, Zurich, Switzerland

Abstract Body Non-melanoma skin cancers (NMSCs) have a growing incidence
worldwide and are strongly influenced by the stroma, of which cancer-associatedfibroblasts (CAFs) are an important component. Consequently, targeting CAFs
is an attractive strategy for NMSC treatment. Recent studies suggest a role ofmitochondria in cell-cell interactions, as intercellular transfer of these organelles
has significant metabolic impacts and occurs between different stromal cell types.
Our research is focused on the transfer of mitochondria from cancer cells to CAFs.
We demonstrated that the transfer of cancer cell-derived mitochondria to fibroblasts
leads to the pro-tumorigenic reprogramming of the latter, both in vitro and in mouseskin tumors in vivo. Using advanced microfluidic probes (FluidFM), we transferredpurified mitochondria from epidermoid carcinoma cells into normal skin fibroblasts,
which induced CAF-like features. Interestingly, mitochondria isolated from nonmalignant cells or less malignant cancer cells failed to induce a CAF phenotype innormal fibroblasts. Mechanistically, we identified a critical role of the mitochondrialtrafficking protein MIRO2 (mitochondrial Rho GTPase 2) in the transfer of cancer cellderived mitochondria to fibroblasts and the subsequent CAF reprogramming. Analysis
of published transcriptome data showed that MIRO2 expression is correlated withhigh malignancy in squamous cell carcinoma (SCC). Knock-down of MIRO2 in SCC
cells reduced the mitochondrial transfer efficacy, prevented skin tumorigenesis inmouse models, and hindered malignant growth in human skin cultures. Therefore, we
propose MIRO2 as a potential therapeutic target for NMSC.

LB1656

LB1657

Associations of single nucleotide polymorphisms on toll-like receptor-4 with risk
of skin cancer

Tie-2 expressing monocytic myeloid-derived suppressor cells represent a
resistance mechanism to anti-PD-1 therapy in melanoma

M. Saleem1, N. Sharafeldin2, T. Callens3, L. Messiaen3, C. A. Elmets1, N. Yusuf1
1
Dermatology, University of Alabama at Birmingham, Birmingham, Alabama, UnitedStates, 2Institute of Cancer Outcomes and Survivorship, University of Alabama at
Birmingham, Birmingham, Alabama, United States, 3Clinical and Diagnostic Sciences,
Medical Genomics Laboratory, Birmingham, Alabama, United States

A. Marguier1, C. Nardin1, 3, B. Ndao1, M. Wespiser2, V. Pereira1, C. Laheurte1,
B. Lecoester1, M. Malfroy1, L. Boullerot1, F. Aubin1, 3, O. Adotévi1, 2
1
Universite Bourgogne Franche-Comte, Besancon, Franche-Comté, France, 2Centre
Hospitalier Universitaire de Besancon Service d'oncologie medicale, Besancon,
Bourgogne Franche-Comté, France, 3Dermatology, Centre hospitalier regional
universitaire de Besancon, Besancon, France

Abstract Body Background: Exposure to ultraviolet (UV) radiation is an establishedrisk factor for skin cancer. Toll-like receptor-4 (TLR4) mediated immune dysregulation
has emerged as a key mechanism for skin cancer in mice. Single nucleotide
polymorphisms (SNPs) on TLR4 gene has been reported to increase or decrease
the susceptibility to various cancers. TLR4 SNP was found to be associated with
progression and survival of melanoma patients. There is limited information on TLR4
SNP and the susceptibility to skin cancer. Objective: To test the association between
TLR4 SNPs and the risk of development of skin cancer. Methods: Skin cancer patientsand controls at University of Alabama at Birmingham completed a cross-sectional
survey on personal and family history of skin cancer as well as on sunscreen use
and tanning proneness. Peripheral blood samples were obtained from participantsand DNA was extracted to genotype the TLR4 SNP. Descriptive analytics were used
to describe the cohort. Multivariable logistic regression models were used to assess
the association of TLR4 SNPs and skin cancer risk. Results: The sample consistedof a cohort of 100 skin cancer patients and 102 controls; 64% of cases and 55.9% ofcontrols were males; 12 (12%) of cases and 17 (16.7%) of controls had any TLR4 SNP.
The most common SNP was D299G in 9 of 12 cases (9.3% overall cases) and 15 of
17 controls (15% overall controls). There was a statistically significant association
between the D299G SNP and skin cancer (Odds ratio (OR) = 0.32, 95%CI: 0.10, 0.99,
p=0.047) adjusting for sex, actinic keratosis, and sunscreen use and reapplication.
Conclusion: Based on our findings from our limited cohort of participants, we found asignificant protective effect for the TLR4 SNP against skin cancer. Validation of thesefindings in a larger cohort is warranted.

Abstract Body Recently, the rate of TIE-2 expressing monocytic myeloid-derived
suppressor cells (TIE-2+ M-MDSC) was described as a negative prognostic marker formelanoma patients. TIE-2 is expressed mainly in the membrane of endothelial cells,
and it is the receptor of the pro-angiogenic factor angiopoietin-2 (ANGPT2). In thisstudy, we investigated the impact of TIE-2+ M-MDSC on response to anti-PD-1 therapy
in advanced melanoma patients. Patients with melanoma treated with anti-PD-1
therapy (n=56) from immunomonitoring cohorts (LYTELOMEL study, NCT02838433)
were studied. Blood samples were collected at baseline before immunotherapy. The
rate of TIE-2+ M-MDSC was analyzed in PBMC by flow cytometry and angiopoietin-2
was dosed by ELISA in serum. Transcriptomic analysis was performed with RNA
sequencing in TIE-2+ M-MDSC. Objectif response rate (ORR) was defined according
to recist criteria. Two groups of patients were discriminated according to the levelof TIE-2 on M-MDSC (threshold at 5,6%): patients with TIE-2High M-MDSC (n=26)
and with TIE-2Low M-MDSC (n=27). ORR was 97% (25/27) in the TIE-2Low M-MDSC
group compared to 50% (13/26) in the TIE-2High M-MDSC group (p=0,0023). A similar
trend was observed in the ANGPT2High group compared to the ANGPT2 Low group(89% vs 60% p=0,079). In contrast, ORR was 39% (n=7/18) in patients exhibiting
high blood levels of TIE-2 M-MDSC and ANGPT2. Transcriptomic analysis of TIE-2
M-MDSC isolated in the context of TIE-2/ANGPT2High signature found that these cells
overexpressed pathways associated with MDSC differentiation, angiogenesis, andimmune suppression. Thus, these results suggest that TIE-2high M-MDSC/ANG2highaxis is involved in primary resistance to anti-PD-1 in melanoma.

10

Carcinogenesis and Cancer Genetics

LB1658Eco-evolutionary profiling of the earliest steps in the skin carcinogenesis
S. Avdieiev1, 3, L. Tordesillas2, K. M. Prieto-Sarmiento2, O. Chavez Chiang2, Z. Chen4,
L. Silva Simoes1, Y. Chen4, N. Andor1, C. Whelan1, 3, R. Gatenby1, 3, E. Flores5, 3,
J. Brown1, 3, K. Tsai2, 3
1Integrated Mathematical Biology, Moffitt Cancer Center, Tampa, Florida, UnitedStates, 2Tumor Biology, Moffitt Cancer Center, Tampa, Florida, United States, 3Cancer
Biology and Evolution Program, Moffitt Cancer Center, Tampa, Florida, United States,
4
Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida, United States,
5
Molecular Oncology, Moffitt Cancer Center, Tampa, Florida, United States

Abstract Body We propose a model that uses ecological and evolutionary principles
to study the sequence of cancer initiation from normal tissue to tumor. We performed
in-vivo serial imaging of clonal dynamics in UV-irradiated SKH-1 K14Cre-ERT2 Confetti
mice paired with targeted DNAseq and scRNAseq. 3-D digitized confocal z-stacks
contained 16,135 clades from the UV exposed (EXP) and 21,506 clades from the nonexposed (NON) skin. The clade size distribution is skewed towards giant clades with
99% percentile of the EXP clades to be on average 2.5 times larger than NON clades.
Giant clades accumulate with chronic UV exposure peaking at 3 months. The largest
EXP clades have 2-4 times higher mutational burden comparing to clades of smaller
size and to NON clades with Kmt2a, Kmt2d, Prex2, and SCN11A as the most mutatedgenes. Giant clades do not typically possess common driver mutations of SCC, e.g.
TP53 and NOTCH. Peak cell density areas (micro-lumps) are clustering within largest
EXP clades with 118 clades having ≥1 micro-lump comparing to 15 NON clades.
Moreover, the number of micro-lumps per EXP clades positively correlates with
mutational burden. scRNAseq of EXP/NON epidermis and tumors revealed dynamicchanges in the cell clusters when progressing from normal to chronically exposed
skin, and then to tumors. Large EXP clones exhibit altered keratinocyte differentiation,
inflammation, and upregulation of metabolic regulators. Based on our framework,
we believe that lesions originate from these large EXP clades as consequence oftissue disruption (Phase 1), long runs of cell divisions permitting the accumulationof mutations (Phase 2) and finally acquiring self-defined fitness function to produce
a lesion (Phase 3).

LB1660Oncogenic RAS signaling induces basement membrane degrading hepsin activity
facilitating progression of skin cancers
D. C. Radicchi1, 2, A. Ardeshirdavani1, 2, C. Gretzmeier2, S. Giesler3, R. Zeiser3, D. Kiritsi2,
A. Nyström2
1
Biological Faculty, University of Freiburg, Freiburg, Germany, 2Department of
Dermatology, Medical Center - University of Freiburg, Freiburg, Germany, 3Departmentof Medicine I, Medical Faculty, Medical Center - University of Freiburg, Freiburg,
Germany

Abstract Body It is increasingly recognized that oncogenic drivers govern behaviorof cancers, including their interaction with and conditioning of the extracellularmatrix. Activating RAS mutations are found in approximately 1/3 of cancers and in
the context of skin, HRAS and NRAS mutations recur in cutaneous squamous cell
cancers and melanoma, respectively. RAS activity in multiple cellular hallmarks ofcancer is well established; however, oncogenic RAS signaling in the establishment of
a tumor-progressing microenvironment has been considerably less explored. In orderfor skin tumors to progress to invasive cancers they need to breech the epidermal
basement membrane (EBM). Previous studies have shown dependence on collagen
VII – laminin-332 interactions in RAS-driven epidermal tumorgenesis via an unknown
mechanism. To understand microenvironmental consequences of oncogenic RAS
signaling in skin, we first investigated mice bearing HrasQ61L-mutated skin tumors andintriguingly observed frequent splits at the level of the EBM. Introduction of HRASQ61L
and HRASG12V in healthy human keratinocytes prompted activation of hepsin, a type
II transmembrane serine protease partially controlled by RAS. Further investigations
in mouse and human models disclosed that hepsin, by cutting the laminin b3 chain
short arm of laminin-332, promotes invasion-facilitating destabilization of the EBM
and evokes suprabasal integrin a6b4. Importantly, expanding the implications of
our findings, melanoma cells stratified with high and low hepsin activity dependingon their NRAS mutational status. Thus, oncogenic RAS facilitates skin cancer
progression through induction of hepsin, which destabilizes the EBM to promoteinvasion. Consequently, topical hepsin-inhibition via e.g. anthralin could be used tolimit progression of RAS-mutated skin cancers.

|

Late-Breaking ABSTRACTS

LB1659

Molecular regulation over metastasis in squamous cell carcinoma and its
implications for drug discovery
S. Quah, R. F. Kabir, P. Sampath
A*STAR Skin Research Labs, Agency for Science Technology and Research, Singapore,
Singapore

Abstract Body Wound healing involves a finely-tuned, self-limiting series of cellularand molecular events orchestrated by transient activation of specific signaling
pathways. Aberrant initiation of wound repair pathways where they are not required
can cause cell behaviors that favor cancer progression. The Follistatin-like 1 (FSTL1)
transcript functions as a molecular switch regulating keratinocyte migration. It
encodes two alternative products with opposite functions – the pro-migratory FSTL1
protein and the anti-migratory microRNA miR-198. Whilst context-specific expressionof these products is essential for coordinating epithelial wound repair, the switch isalso hijacked by tumor cells to enhance their migration and invasion in squamous cell
carcinoma (SCC). I will discuss regulatory pathways upstream of the miR-198/FSTL1
switch, events downstream of the switch that alter cell migratory behavior, as well
as how we may use this knowledge in the search for anti-metastatic therapeutics.

LB1661The differences between human skin and skin warts in the nanoscale distributionof nuclear speckle-associated phospholipids revealed by quantitative superresolution microscopy
P. Hoboth1, 4, M. Sztacho1, A. Quaas2, B. Akgul3, P. Hozak1
1
Ustav molekularni genetiky Akademie ved Ceske republiky, Prague, Czechia, 2Instituteof Pathology, Universitatsklinikum Koln, Cologne, Nordrhein-Westfalen, Germany,3
Institute of Virology, Universitatsklinikum Koln, Cologne, Nordrhein-Westfalen,
Germany, 4Univerzita Karlova Prirodovedecka fakulta, Prague, Czechia

Abstract Body Chronic human papillomavirus (HPV) infection of the cutaneous skincan be asymptomatic or cause benign skin warts, premalignant actinic keratosis
or malignant squamous cell carcinoma. A novel hallmark of HPV-mediatedcarcinogenesis is increased level of nuclear phosphatidylinositol 4,5-bisphosphate(nPI(4,5)P2). Nuclear speckles (NS) represent the largest pool of nPI(4,5)P2. Here,
we used quantitative multicolor stimulated emission depletion (STED) nanoscopy
to study the nanoscale distribution of the nPI(4,5)P2 with respect to the NS marker
SON in human clinical formalin-fixed paraffin-embedded (FFPE) skin and HPV warts.
Imaging of human clinical FFPE tissue sections provides insights into healthy anddiseased states and therefore represents a valuable resource for basic research,
as well as for diagnostic and clinical purposes. Nevertheless, conventional lightmicroscopy obscures the molecular details of the tissue and cell architecture dueto the diffraction barrier of light. Nanoscopy overcomes this limitation and provides
access to the nanoscale details of tissue and cell organization. The implementationof multicolor STED nanoscopy in human clinical FFPE skin and wart sections allowed
us to quantitatively show at nanoscale the higher levels of NS-associated PI(4,5)P2
in HPV-induced warts compared to control skin. These data expand the previous
reports of HPV-induced increase of nPI(4,5)P2 levels and reveal for the first time
the functional, tissue-specific architecture of nuclear lipid and protein antigens inclinically relevant samples. Moreover, our quantitative super-resolution microscopyof FFPE tissue sections is applicable to investigate other dermatologically relevant
nanoscopic details in healthy and diseased tissues.

11Carcinogenesis and Cancer Genetics

LB1662

Photodynamic therapy reduces the burden of small epidermal clones in human skin
L. Wei1, F. E. Megan2, M. Murakami1, L. Yan1, S. Grant2, Q. Hu1, B. Okai1, P. Singh3,
E. Remenyik4, E. Gellen2, B. A. Foster5, W. J. Huss2, G. Paragh2
1
Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center,
Buffalo, New York, United States, 2Dermatology, Roswell Park Comprehensive Cancer
Center, Buffalo, New York, United States, 3Genomics Shared Resource, Roswell Park
Comprehensive Cancer Center, Buffalo, New York, United States, 4Dermatology,
Debreceni Egyetem, Debrecen, Hajdú-Bihar, Hungary, 5Pharmacology & Therapeutics,
Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States

Abstract Body Keratinocyte carcinomas (KCs) and actinic keratoses (AKs) usuallyarise after decades of UV exposure in field-damaged skin through the accumulationof clonal mutations (CMs) in keratinocytes. We previously found that low variant allele
frequency (low-VAF, defined as <1% ) CMs in normal sun-damaged skin correlated with
KC burden. Photodynamic therapy (PDT) has excellent efficacy in the treatment ofboth AKs and early KCs while reducing KC risk, but the effect of PDT on the underlying
field of CMs has yet to be understood. In the current study, we assessed the burdenof CMs after PDT to understand the effect of PDT on subclinical field damage. We
performed an ultradeep targeted sequencing (UTS, size=248kB) of clinically normalskin samples from 5 patients undergoing red light delta-aminolevulinic acid PDT totreat AKs. Four 7mm2 epidermal samples were taken before and 1-2 months after
PDT. The 8 epidermal DNA samples per patient were sequenced with UTS to reacha median coverage of 32,336X, and mutation profiles before and after PDT werecompared. We found a significant reduction in the overall low-VAF CMs (p=0.028) inthe 5 patients after PDT compared to pre-PDT. The greatest changes in low-VAF CMs
were observed in the three facial cases (ranging from -42% to -50%; only face cases:
p=0.006), compared to the forearm (-34%) and hand (+18%) cases. Only the single
hand PDT treatment case demonstrated an increase in low-VAF CMs after PDT, whichaligns with the documented lower efficacy of PDT at acral sites. Our data provide
evidence for the effectiveness of PDT in modifying the subclinical CMs burden andsuggest that CMs are a marker for field treatment efficacy.

|

Late-Breaking ABSTRACTS

LB1663A multi-gene prognostic signature associated with cutaneous squamous cell
carcinoma metastasis
J. Wang1, C. Harwood1, E. Bailey1, F. Bewicke-Copley1, C. Anene1, J. Thomson1,
M. Qamar1, C. Nourse2, C. Schoenherr2, M. Treanor-Taylor2, E. Healy3, C. Lai3, P. Craig4,
C. Moyes5, W. Rickaby6, J. Martin1, C. Proby7, G. Inman2, I. Leigh11Queen Mary University of London Faculty of Medicine and Dentistry, London,
United Kingdom, 2Cancer Research UK Beatson Institute, Glasgow, United Kingdom,3
Dermatopharmacology, University of Southampton, Southampton, United Kingdom,
4
Cellular Pathology, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham,
Gloucestershire, United Kingdom, 5Queen Elizabeth University Hospital, Glasgow,
United Kingdom, 6University College London Faculty of Medical Sciences, London,
United Kingdom, 7University of Dundee, Dundee, United Kingdom

Abstract Body cSCC staging methods are reported to have sub-optimal
performances in metastasis prediction. Accurate identification of patients withtumors at high risk of metastasis would have a significant impact on management.
Archival FFPE tissue from primary cSCC with perilesional normal tissue from 237
immunocompetent patients (151 non-metastasizing and 86 metastasizing) werecollected retrospectively from four centers. All pathology was centrally reviewed
and T-staged by consensus. TempO-seq was used to probe the whole transcriptome
and machine learning algorithms were applied to derive predictive signatures, with
a 75%:25% split for training and testing datasets. A 20-gene prognostic model wasdeveloped and validated, with an accuracy of 86.0%, sensitivity of 85.7%, specificityof 86.1%, and positive predictive value of 78.3% in the testing set. A linear predictor
was also developed, significantly correlating with metastatic risk. This has provided
biological insights into the process of metastasis and potential therapeutic targets.
There are biological and genomic mechanisms common to cSCC across different
tissue types and the prognostic signature may provide further insights into common
differentiation and stem-like pathways underpinning cSCC. Ultimately, the 20-gene
prognostic signature has the potential to be incorporated into clinical workflows for
cSCC to significantly improve risk stratification, identify patients with high-risk cSCC
who may benefit from adjuvant treatment and reduce overtreatment for patients with
low-risk cSCC.

LB1664

LB1665

C. Johnson1, S. Solhjoo2, I. Ali1, K. Nash1, L. Morina2, R. Sweren1, W. Timp2
Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland,
United States, 2Johns Hopkins University, Baltimore, Maryland, United States

L. Syu1, S. Mishra1, R. Wu2, D. Wilbert1, R. Ryan2, K. Cho2, A. Dlugosz1
Dermatology, University of Michigan Michigan Medicine, Ann Arbor, Michigan, UnitedStates, 2University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Abstract Body Twenty-five percent of early-stage mycosis fungoides (MF) patients
will develop the advanced-stage disease with higher mortality and poorer prognosis.
Understanding disease diagnosis and progression is imperative, as the clinical stageof the disease is the only validated prognostic marker of survival in MF. Early-stage
MF disease is associated with high levels of cancer-associated fibroblasts (CAFs)
characterized by CXCL12 and FAP-α genes, which may be responsible for tumor
cell migration and drug resistance. Subtypes of CAFs have been identified in thetumor microenvironment of multiple solid and hematological malignancies, playa role in supporting tumor growth, and are associated with worsening prognosis.
CAF subtypes have yet to be identified in lesional MF tissue. We applied single-cell
RNA sequencing to skin tissue from unaffected, early-stage MF, and late-stage MF
patients. Comparing the fibroblast subtypes populations demonstrates more diversity
in MF versus non-MF tissues. The MF fibroblast populations included four major CAF
subtypes: inflammatory CAFs, myofibroblast CAFs, antigen-presenting CAFs, andMF-specific CAFs. Our data suggests a trend in which CXCL12 expression is higher
in early-stage MF than in late-stage disease. In contrast, FAP-α expression is higher
in late-stage than in early-stage MF disease. Our findings suggest that early-stage
MF disease may be better diagnosed with CXCL12 fibroblast markers as opposed to
FAP-α. Further molecular studies are needed to validate these results and determine
their role in the diagnosis and prognosis of MF.

Abstract Body Tumorigenesis is driven by accumulation of somatic alterations
in multiple cancer driver genes, including tumor suppressors and oncogenes.
Conventional mouse models have yielded important insights into the molecularbasis of cancer, but engineering several genetic alterations in vivo is expensive,
time-consuming, and labor-intensive. Here we show that CRISPR/Cas9 technology
can be used to disrupt multiple tumor suppressor genes in epidermal cells of adultmice, leading to squamous papilloma development. Transgenic “PRN” mice weregenerated that constitutively express sgRNAs targeting the tumor suppressor genes
Trp53, Rb1, and Nf1. To disrupt gene expression in postnatal mouse epidermis we
generated iK14;Cas9;PRN mice carrying a tamoxifen-activated epidermal Cre allele(K14-CreERT), a Cre-inducible Cas9 allele (R26-LSL-Cas9), and the PRN allele. Mice
were treated with tamoxifen at 7.5 weeks to induce Cas9 expression and monitor for
tumor development. Four out of 5 iK14;Cas9;PRN mice developed focal hyperkeratotic
skin tumors 5 to 9.5 months after starting tamoxifen treatment, with H&E histology
showing squamous papillomas. Sanger sequencing revealed successful editing of
Trp53 in 6/8, Rb1 in 8/8, and Nf1 in 8/8 tumors. Surprisingly, two iK14;Cas9;PRN
mice and one Cas9;PRN mouse developed liver lesions with histology resemblinga lymphoid or other hematopoietic malignancy suggesting ectopic and ‘leaky’ Cas9
expression, even in the absence of Cre recombinase. Our data establish the utilityof CRISPR/Cas9 for editing multiple target genes simultaneously in epidermis using
multi-guide transgenic mice, setting the stage for functional validation of candidate
cutaneous cancer drivers using an approach considerably less cumbersome thanconventional mouse modeling. Further modifications are required to ensure tightcontrol of Cas9 expression, which is needed to avoid tumor development in nontargeted tissues.

Single-cell RNA sequencing of cancer-associated fibroblasts suggests a differential
role for CXCL12 and FAP-α in early vs. late-stage mycosis fungoides disease.

1

CRISPR/Cas9-mediated genome editing in postnatal epidermis drives squamous
tumor development

112Cell-Cell Interactions in the Skin

LB1666|Late-Breaking ABSTRACTS

LB1667

Psoriatic neutrophils are primed in circulation by calprotectin for enhanced
inflammatory response in dermal vasculature.

Successful treatment of rare linear lichen planopilaris with ixekizumab

S. Simon1, 2, S. T. Hwang2, G. Garcia1
1
Biomedical Engineering, University of California Davis College of Engineering, Davis,
California, United States, 2Dermatology, University of California Davis, Davis, California,
United States

1

Abstract Body
The role of neutrophils in psoriasis has re-emerged as an exciting avenue of researchfollowing the discovery that they are a source of neutrophil extracellular traps (NETs)
in skin. The extent to which cytokines and damage-associated molecular patternsDAMPs (Calprotectin S100A8/A9) correlate with the level of neutrophil priming
in the circulation and their capacity to recruit to inflamed skin is unknown. We
hypothesized that calprotectin in circulation primes neutrophils by activating CD18
adhesion receptors and increasing their capacity to arrest on dermal vasculature.
Whole blood was collected and calprotectin in serum determined by ELISA andadhesion receptors was determined by flow cytometry. A vascular mimetic flowchamber enabled quantitation of neutrophil recruitment on glass coated withrecombinant E-selectin and ICAM-1. Psoriatic neutrophils in blood expressed 2.5-foldhigher CD11b receptors and 30% lower L-selectin compared with healthy subjects,
consistent with degranulation and proteolytic shedding. This coincided with a 3-foldincrease in expression of high affinity CD18 on psoriatic versus healthy neutrophils(p<.005). Plaque psoriasis is characterized by a large influx of neutrophils. Mimicking
vascular hydrodynamics and inflammation in microfluidic channels, we probed thecapacity of primed neutrophils to recruit on a substrate of E-selectin and ICAM-1.
Consistent with CD18 activation, the fraction of perfused neutrophils that rolled toarrest on E-selectin and ICAM-1 was 36% higher in psoriatic versus healthy donors.
Calprotectin was higher in psoriatic than healthy serum (1.84 vs 4.21 ug/ml, p<.01)
and a tight correlation was detected between a patient’s serum calprotectin, thenumber of high affinity CD18, and an elevation in arrest efficiency. We conclude
that psoriatic neutrophils are primed in circulation by exposure to calprotectin forenhanced arrest at vascular sites of inflammation by activated CD18.

H. Ahmed1, 2, 3, M. Petkar1, M. Steinhoff1, 4
Hamad Medical Corporation, Doha, Ad Dawhah, Qatar, 2Weill Cornell Medicine, New
York, New York, United States, 3Health Sciencea, King's College London, London, United
Kingdom, 4Qatar University College of Medicine, Doha, Ad Dawhah, Qatar

Abstract Body Lichen planopilaris (LPP) is a lymphocytic primary cicatricial alopecia
characterized by perifollicular erythema, follicular hyperkeratosis and scaring,
resulting in permanent hair loss.1 Current treatment modalities, both topical andsystemic, fail to achieve satisfactory and consistent results.2-4 As therapies fail tohalt the inflammatory process, patients with LPP may face long-term disfigurement
and significant psychological burden.5 Thus, efficacious, safe and targeted therapies
are a high priority in preventing disfiguring alopecia in patients with LPP. Here, wereport on a case of rare LPP in linear distribution (LLPP) involving the scalp andforehead achieving complete hair regrowth after 12 weeks of treatment with an antipsoriatic, anti-interleukin (IL)-17A/F antibody (Taltz, Ixekizumab, Lilly). The present
case underlines the viability of ixekizumab as a possible first-line, targeted therapy
for LPP and its variants with sustained efficacy.

LB1668

LB1669

M. Shim1, S. Choi1, H. Kim1, S. Beak2, N. Jeon1
1
Mechanical Engineering, Seoul National University College of Engineering, Seoul,
Korea (the Republic of), 2Biological Sciences, Seoul National University College of
Natural Sciences, Seoul, Korea (the Republic of)

S. Choi1, M. Shim1, J. Lee1, H. Kim1, S. Beak2, N. Jeon1
Mechanical Enginnering, Seoul National University, Seoul, Korea (the Republicof), 2Biological Sciences, Seoul National University, Gwanak-gu, Seoul, Korea (theRepublic of)

Abstract Body Recently, the use of non-animal models to test cosmetics is crucial
following the ban on animal testing. Our in-vitro skin-on-a-chip model offers many
advantages over conventional testing methods and enhances the ability to modelskin structure. The miniaturized skin-on-a-chip device is fabricated using a highresolution DLP 3D printer and has a mesh structure of many pores, allowing forhigh-throughput screening. The model co-cultures keratinocytes, melanocytes, andfibroblasts in a 3D fibrin gel extracellular matrix to model the skin barrier that consistsof multiple cell layers to form the epidermis and dermis layers. We used RFP-labeled
normal human dermal fibroblasts (NHDF) and immortalized keratinocytes (HaCaT),
which are modified to show LC3 expression. Higher LC3 expression indicates theactivation of autophagy, which can enhance the anti-aging effect. To obtain a 3D coculture model of skin layers, dermal fibroblasts were first placed in the middle of thedevice, then melanocytes and keratinocytes were added on top of the fibroblasts toform the air/liquid interface. Cell culture media was added under the fibroblast layer
via a specially designed microfluidic compartment. We tested Ageraline, Eperuline,
Beach vitex, Saururus Chinensis, Dermagenist, and Chronoglow, which are skin carecompounds with anti-aging effects targeting keratinocytes and dermal fibroblasts.
LC3 expression levels in compounds-treated HaCaT and NHDF were increased
compared to the control group, with Beach vitex and Saururus Chinensis showing
the higher intensity of LC3 expression. Our in-vitro skin-on-a-chip model provides
a versatile and high-throughput approach for evaluating the efficacy of cosmetic
products, accelerating the development of new anti-aging therapies, and reducing thereliance on animal testing. This platform can also be used for testing and analyzing
various skin care cosmetics and modeling skin diseases in the future.

Abstract Body We present a miniaturized in-vitro skin model fabricated using organ
on a chip technology. The importance of non-animal models to test cosmetics has
increased since the European Union banned animal testing for cosmetic products.
Our model offers advantages over conventional methods and can provide reliable andcost-effective results. Our in-vitro skin model is fabricated using a high-quality DLP 3D
printer with a bio-compatible resin, enabling high throughput screening. It allows coculture of 3 different cell types - keratinocyte, melanocyte, and fibroblast in a 3D fibrin
gel extra cellular matrix, mimicking the physiological environment of human skin.
To obtain the 3D co-culture model of miniaturized skin, dermal fibroblasts were firstplaced in the middle of the device and melanocytes and keratinocytes were addedon top of the fibroblasts to form the air-liquid interface. The cell culture media wasadded under the fibroblast layer via a specially designed microfluidic compartment.
The model was then used to test the effects of 6 different chemicals that havepotential effects on skin elasticity and skin whitening, which can influence skin aging.
Testing skincare compounds within the platform showed an increasing trend ofcollagen I and elastin expressions for compounds that aim to increase skin elasticity,and decreasing melanin expression for compounds that aim to whiten the skin. Thismodel provides a realistic and reproducible system for testing cosmetic formulations
and their safety profiles, as well as the evaluation of active ingredients. The ability to
co-culture different cell types in a 3D environment has the potential to provide a moreaccurate representation of skin biology than traditional 2D culture systems. Overall,
our miniaturized in-vitro skin model on a chip offers a promising alternative to animal
testing for cosmetics, and has the potential to improve the accuracy and efficiency ofsafety assessments for cosmetic products.

Anti-aging effects of autophagy analyzed within a 3D microfluidic skin-on-a-chip forskin cosmetics testing

Development and characterization of a miniaturized in-vitro skin model on a chip forhigh-throughput cosmetic testing1

13

Cell-Cell Interactions in the Skin

LB1670|Late-Breaking ABSTRACTS

LB1671

Activation of pro-fibrotic processes downstream of IL-31RA signaling distinguishes
prurigo nodularis from atopic dermatitis

Large-scale skin scRNA-seq profiling highlights distinct body site-specific ligandreceptor interactions and pathways in keratinocytes

P. D. Chaskar1, F. Ma2, W. Van Delm1, C. Piketty1, V. Julia1, J. Krishnaswamy1,
J. Gudjonsson2
1
Galderma SA, Lausanne, VD, Switzerland, 2Department of Dermatology, University ofMichigan, Ann Arbor, Michigan, United States

R. Wasikowski1, M. T. Patrick1, Q. Li1, Q. Nie2, B. Andersen3, M. Plikus2,
J. M. Kahlenberg4, A. Billi1, L. Tsoi1, J. Gudjonsson1
1
Dermatology, University of Michigan, Ann Arbor, Michigan, United States,2
Developmental and Cell Biology, University of California Irvine, Irvine, California,
United States, 3Medicine, University of California Irvine, Irvine, California, United States,
4
Rheumatology, University of Michigan, Ann Arbor, Michigan, United States

Abstract Body Introduction: The neuro-immune cytokine interleukin 31 (IL-31) is a
key mediator in the pathophysiology of atopic dermatitis (AD) and prurigo nodularis(PN). Blocking IL-31 signaling with the anti-IL31RA antibody nemolizumab improves
pruritus and skin lesions in AD and PN, but the underlying mechanisms are notfully understood. PN is a debilitating chronic inflammatory disease characterized
by chronic pruritus and pruriginous lesions. Molecular characterization of PN
lesions revealed neuroinflammation, Type 2 and Type 17 inflammatory responses,
dysregulated epidermal differentiation, and fibrosis, many of which were reversed
following nemolizumab treatment. Objectives: Define cellular mediators andmolecular signaling cascades in AD and PN. Materials and Method: We performed
single-cell RNA sequencing of lesional (6 AD and 6 PN), non-lesional (3 AD and 3 PN)
and healthy controls (15) skin biopsies. In addition, we performed spatial sequencing
on 3 AD and 3 PN lesional skin biopsies from patients. Results: Our analysis reveals
that AD and PN are characterized by major transcriptomic shifts involving multiple cell
types. Strikingly, we found that PN can be distinguished from AD by the dominance of
COL11A1+ fibroblasts upregulating multiple pro-fibrotic processes. Further analyses
in PN show dynamic interactions of fibroblasts and keratinocytes with immune cells,
driving activation of TGFb-related signaling pathways. Lastly, we found that PN
skin keratinocytes and fibroblasts express IL-31RA, and confirmed decreased profibrotic and inflammatory signatures, and normalized epidermal differentiation uponnemolizumab treatment. Conclusions: This study reveals that while IL-31RA signaling
is key in AD and PN, unique molecular interactions and signaling cascades drive
distinctly different pathophysiologies in these diseases.

Abstract Body The skin varies greatly across anatomic sites, both in thickness andtexture, with each site prone to different skin disorders. However, a comprehensive
understanding of skin biology and cell-cell interactions has been lacking but can shedlight on the underlying biological mechanisms contributing to body site variation inskin disease. To address this, we conducted scRNA-seq on 96 biopsies from 51
healthy individuals, including 7 anatomic sites: face, scalp, axilla, palmoplantar, arm,leg, and back skin. Among the 274,834 cells, we focused on epidermal function throughanalyses of 87,213 keratinocytes from 4 different subtypes (basal, differentiated,keratinized, and cycling), along with hair follicle keratinocytes and Merkel cells.
Focusing on cell-cell interactions, we detected 36 significant (p < 0.05) signaling
pathways, 11 of which were shared among the 7 anatomic sites. Interestingly, 4 and 1of these pathways were unique to facial and palmoplantar skin, respectively. Notably,
palmoplantar skin uniquely had enriched Tenascin signaling, which has a role inmaintaining extracellular matrix integrity, but palmoplantar skin lacked PARs andMIF signaling, which are involved in protease activation and macrophage recruitment
and retention, respectively. Accordingly, TNC was upregulated in palmoplantar skin,while genes associated with the PAR and MIF pathways (e.g., ACKR3 and EGFR) were
downregulated. Facial skin uniquely showed significant activity of WNT, TGFb, andTRAIL pathways, with upregulation of BMP7, ITGB1, and TNFRSF10B. These findings
demonstrate shifts in cell-cell communication across anatomic sites providing
critical information to explain disease predisposition to specific regions of the skin.

LB1672

LB1673Senescent melanocytes in nevus skin stimulate hair growth
X. Wang1, R. Ramos1, N. Shettigar1, Q. Nie2, M. Plikus1
1
Developmental and Cell Biology, University of California Irvine, Irvine, California, UnitedStates, 2Mathematics, University of California Irvine, Irvine, California, United States

Abstract Body Cell fate in tissues is tightly regulated by complex signaling networks.
In mammalian skin, hair follicles (HFs) undergo periodic cycles of growth (anagen),regression (catagen), and rest (telogen), which are closely coordinated by short- andlong-range signals emanating from HF niche cells and neighboring extra-follicular
cells. Although HF cycle is typically well-regulated, excessive hair growth rarely
occurs. A persistent anagen phenotype is commonly observed in hairy melanocytic
nevi in humans, suggesting hyperactivation of HF stem cells. Compared to normalskin, nevus skin contains large numbers of dermal melanocytes that enter thestate of oncogene-induced senescence (OIS). To better understand the underlying
mechanism driving hairy nevus phenotype, we used both congenital and acquired
nevus mouse models, in which OIS is genetically induced in melanocytes, to identify
key hair growth-modulating signaling regulators in senescent melanocytes. ThroughRNA-seq analyses on melanocytes and HF stem cells, we uncovered differentiallyexpressed gene patterns specific to nevus skin cells. Via functional experiments
in mice, that include gain- and loss-of-function assays on signaling ligands andreceptors, we revealed lead senescence-associated secretory phenotype (SASP)
factor that potently promotes HF stem cell activity, contributing to excessive hair
growth in nevus skin. Our findings suggest that SASP factors can have beneficial
effects on tissue regeneration and highlight novel strategy for stem cell andhair growth activation by targeting SASP-enriched pathways. These results havetantalizing implications for developing new therapeutic approaches for hair loss andtissue regeneration disorders.

Development of an in vitro assay to evaluate the responsiveness of itch-related
nerves using human-induced pluripotent stem cell-derived sensory neurons.
M. Satoh2, 1, M. Fujita2, 1, S. Toyama3, T. Yoshino2, 1, Y. Kamata1, 3, T. Sakurai2, 1,
Y. Suga1, 4, M. Tominaga1, 3, K. Takamori1, 3, 4
1Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of
Medicine, Urayasu, Chiba, Japan, 2FANCL Research Institute, FANCL Corporation,
Yokohama, Kanagawa, Japan, 3Juntendo Itch Research Center (JIRC), Institute forEnvironmental and Gender-Specific Medicine, Juntendo University Graduate Schoolof Medicine, Urayasu, Chiba, Japan, 4Department of Dermatology, Juntendo University
Urayasu Hospital, Urayasu, Chiba, Japan

Abstract Body Sensitive skin is characterized in several ways. One of them includes
alterations in neuronal morphology, and a consequent sensation of itching. Itching
can lead to a decrease in quality of life. We have, accordingly, recently developed anassay using human-induced pluripotent stem cell-derived sensory neurons (hiPSCSN) as a model for human sensory nerve cells, to elucidate the external factors
contributing to the development or exacerbation of sensitive skin. Previous studies
have shown that exposure to cosmetic ingredients and air pollutants may induce
morphological alterations in hiPSC-SNs, such as neurite outgrowth or retraction,
increase in the number of blebs, and changes in the expression of nicotinamidemononucleotide adenylyl transferase 2 (NMNAT2). In this study, we attempted todevelop an experimental system using hiPSC-SNs to evaluate the responsivenessof sensory neurons to itch stimuli, by measuring calcium influx in response topruritogens. The responsiveness of hiPSC-SN to histamine, chloroquine, BAM8-22,
allyl isothiocyanate (AITC) (TRPA1 agonist), and capsaicin (TRPV1 agonist) was
examined with calcium imaging, and we confirmed that it responded to all thesesubstances. This data suggests that hiPSC-SN may be used as a model to evaluate
the responsiveness of itch-related human sensory nerves. This model is expected to
be useful in elucidating the effects of external factors, such as chemical substances,on the responsiveness of sensory nerves to itching; and to unravel the molecularmechanisms underlying these effects.

14Cell-Cell Interactions in the Skin

LB1674A roadmap for the human skin cell atlas
A. Almet1, 2, H. Yuan3, K. Annusver3, R. Ramos2, 4, Y. Liu4, J. Wiedemann4, 5,
D. Sorkin5, 6, N. Xu Landén7, E. Sonkoly8, 7, M. Haniffa9, Q. Nie1, 2, 4, B. M. Lichtenberger10,
M. Luecken11, 12, B. Andersen2, 5, L. Tsoi13, 14, F. M. Watt15, 16, J. Gudjonsson13,
M. Plikus2, 4, M. Kasper3
1
Mathematics, University of California Irvine, Irvine, California, United States, 2NSFSimons Center for Multiscale Cell Fate Research, University of California Irvine,
Irvine, California, United States, 3Cell and Molecular Biology, Karolinska Institutet,
Stockholm, Sweden, 4Developmental and Cell Biology, University of California Irvine,
Irvine, California, United States, 5Medicine, University of California Irvine, Irvine,
California, United States, 6Institute for Clinical and Translational Science, University ofCalifornia Irvine, Irvine, California, United States, 7Medicine Solna, Karolinska Institutet,
Stockholm, Sweden, 8Medical Sciences, Uppsala Universitet, Uppsala, Sweden,
9
Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, Tyne andWear, United Kingdom, 10Dermatology, Medizinische Universitat Wien, Wien, Austria,
11
Institute of Computational Biology, Helmholtz Munich, Munich, Germany, 12Instituteof Lung Health & Immunity, Helmholtz Munich, Munich, Germany, 13Dermatology,
University of Michigan, Ann Arbor, Michigan, United States, 14Department of
Biostatistics, University of Michigan, Ann Arbor, Michigan, United States, 15European
Molecular Biology Laboratory, Heidelberg, Germany, 16Centre for Gene Therapy andRegenerative Medicine, King's College London Faculty of Life Sciences & Medicine,
London, United Kingdom

Abstract Body Single-cell technologies have become essential in investigative
dermatology. Despite the multitude of available datasets, a central reference atlasof normal human skin is still lacking. As part of the global Human Cell Atlas (HCA)
initiative, we have assembled a skin biological network to build a Human Skin Cell
Atlas (HSCA) and outline a roadmap toward that goal. Here, we will present the driversof skin diversity to be considered, hurdles that impede comprehensive representation,and technical considerations for tissue processing and computational analysis. We
will also show a first snapshot of our ongoing large-scale human skin scRNA-seq
data integration. Overall, we outline the goals for the Atlas 1.0 – representing a global
effort to accelerate the discovery of new aspects in skin biology – and invite you tojoin us in building a consensus human skin cell atlas.

|

Late-Breaking ABSTRACTS

LB1675Uniquely identified cell type in atopic dermatitis may provoke and maintain thechronic itching sensation through interaction with dorsal root ganglion neuron
S. Kim1, J. Park1, H. Kim1, 2, K. Zhang1, 2, Y. Kim1, W. Kim1, T. Kim1, 2, K. Park3, J. Choi4, L.
Kim1, C. Park1, 2
1
Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of),2
Yonsei University Brain Korea 21 Project for Medical Science, Seodaemun-gu, Seoul,
Korea (the Republic of), 3Incheon National University, Incheon, Korea (the Republic of),4
Korea University Medicine, Seoul, Seoul, Korea (the Republic of)

Abstract Body Atopic dermatitis is a chronic and relapsing skin condition with agrowing prevalence worldwide. One of the key symptoms is intense itching, which
severely impacts the quality of life. Recently, there has been increased attention to
the interactions between the Th2-skewed immunological environment of skin lesions
and nerve fibers/neuronal cell bodies in the dorsal root ganglion (DRG). To elucidate
the interaction mechanism between the peripheral nervous system and cutaneous
immune response, we tried to use the published single cell omics dataset (esp. single
cell RNA sequencing) of AD skin and DRG. After that, through immunofluorescencestaining, the expression of nerve fibers, immune cells, and fibroblast-related
genes were screened in human skin. Nerve fibers were found to be predominantly
distribution of nerve fibers was much higher in AD skin compared to healthy skin.
Furthermore, colocalization of immune cells/fibroblast and nerve fibers wasobserved in AD skin, indicating that there is interaction between DRG and immune
cells/fibroblasts. Few studies have attempted to link the single-cell RNA sequencing
datasets of inflammatory skin diseases and DRG. Our report is the first attempt tolist up the potential molecular/cellular pairs which is thought to be involved in theaxon elongation, peripheral sensitization in the AD-specific Th2 skewed inflammation
circumstances. These translational approach would shed light on the understandingof the patho-mechanisms underlying the chronic itching sensation in AD. Keywords:
Atopic Dermatitis, Single Cell Omics, Cell-to-Cell Interactions, pruritus, dorsal root
ganglion

LB1676

Hibiscus sabdariffa-derived peptide, Gly-Pro (GP) has potent antifibrotic effects byregulating the serine-glycine biosynthesis pathway
H. Kim1, Y. Jang1, D. Seo1, S. Lee2, S. Moh2, S. Choi5, L. Germain3, D. Kim4, J. Shin4
Biology, CHA University - Bundang Campus, Seongnam, Gyeonggi-do, Korea (theRepublic of), 2Plant Cell Research Institute, BIO-FD&C Co., Ltd,, Incheon, Korea (theRepublic of), 3Faculty of Medicine, Université Laval, CHU de Québec-Université Laval
Research Centre, QC G1J1Z4, Quebec, Canada, 4CHA Bundang Medical Center,Seongnam, Gyeonggi-do, Korea (the Republic of), 5Daesang Holdings Co., Ltd, Seoul,
Korea (the Republic of)1

Abstract Body Background: TGF-b1 is the key fibrotic cytokine that regulates theexpression of activating transcriptional factor 4 (ATF4) and activates the serineglycine biosynthesis pathway required for enhanced collagen production. Although
Hibiscus sabdariffa extract has been reported to regulate collagen synthesis,
the exact mechanism has not been elucidated yet. Objective: In this study, we
synthesized dipeptides containing proline derived from Hibiscus sabdariffa plant
cells and evaluated their effect on collagen synthesis. We also investigated themechanism of action. Method: We induced plant cells of Hibiscus sabdariffa fromleaf tissue and identified seven dipeptides: Ala-Pro, Asn-Pro, Arg-Pro, Ser-Pro, ValPro, Tyr-Pro, and Gly-Pro (GP). We then treated human dermal fibroblasts (HDF) withthese dipeptides, with or without TGF-β1. RT-qPCR and Western blot analysis were
performed to elucidate the mechanism of action. Results: Among the dipeptides
identified, GP significantly suppressed the expression of collagen in HDF. Additionally,
GP suppressed the phosphorylation of Smad2/3 and decreased the expression of
ATF4, which is up-regulated by TGF-β1. Furthermore, GP significantly decreased themRNA expression of other enzymes involved in serine-glycine biosynthesis, such as
SLC2A1, PHGDH, PSAT1, and PSPH. Conclusion: Our findings suggest that Hibiscus
sabdariffa-derived peptide, GP has potent antifibrotic effects by regulating the serineglycine biosynthesis pathway.

15

Clinical Research – Epidemiology and Observational Research

LB1677First results from the observational up-tained study on effectiveness anddisease control in patients with moderate to severe atopic dermatitis treated withupadacitinib.
S. Weidinger1, T. Schadeck6, D. Mortazawi4, P. Häusler-Mehlhorn5, C. Lupp2,
T. Mosch2, B. Fritz2, F. Lauffer3
1
Dermatology and Allergy, Universitatsklinikum Schleswig-Holstein, Kiel, SchleswigHolstein, Germany, 2AbbVie Deutschland GmbH & Co KG, Wiesbaden, Hessen,
Germany, 3Dermatology and Allergy, Technische Universitat Munchen, Munchen,
Bayern, Germany, 4Dermatology Practice, Remscheid, Germany, 5Dermatology Practice,Chemnitz, Germany, 6Dermatology Practice, Bogen, Germany

Abstract Body Upadacitinib (UPA) was shown to be effective and safe in moderate
to severe atopic dermatitis (AD) in clinical trials. The UP-TAINED study aims at
generating real-world evidence, with a particular focus on early and sustained disease
control, tolerability, and safety. This prospective, multicenter, non-interventional study
includes patients aged ≥12 years with moderate to severe AD treated with UPA 15
or 30 mg QD. Key outcome parameters are Atopic Dermatitis Control Tool (ADCT),
Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI) and
Worst Pruritus Numerical Rating Scale (WP-NRS). Further, treatment-emergent
adverse events (TEAE) and AEs of interest are collected. Disease control is defined as
ADCT total score of <7 at week 12. For this interim analysis, data on 121 patients withbaseline and follow-up visits at weeks 4 and 12 were analyzed descriptively. Meanage was 41.9 years. The initial UPA dose was 30mg in 70.2%, and UPA was used
as monotherapy in 45.5% of the patients. Mean EASI at baseline was 21.6 (±13.9),
DLQI 13.0 (±6.8), and WP-NRS 7.1 (±2.0), respectively. At week 12, mean EASI had
decreased to 2.5 (±4.1), DLQI to 3.2 (±3.3), and WP-NRS to 1.9 (±2.1). The proportionof patients with adequately controlled disease increased from 4.1% at baseline to
73% at week 12. 63.3% and 36.7% of patients achieved EASI 90 and EASI 100 atweek 12. 43 patients experienced TEAE, all were mild (75.3%) or moderate (24.7%),
1 serious in UPA 30 mg (abscess), no new safety signal was detected. These firstreal-world data confirm that UPA leads to clinically meaningful improvements of thedisease burden and the overall favourable safety profile in patients with moderate tosevere AD.

LB1679Atopic dermatitis and cognition in children
P. G. Sockler1, S. R. Hooper2, E. Ma3, K. Kartawira1, J. Wan1
Dermatology, Johns Hopkins Medicine, Baltimore, Maryland, United States, 2Health
Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,
United States, 3Dermatology, University of Maryland School of Medicine, Baltimore,
Maryland, United States

1

Abstract Body Recent data suggest a link between atopic dermatitis (AD) andcognitive problems, but few longitudinal studies contain robust measures of both AD
and cognition. To assess effects of childhood AD on general cognition, we examineda UK-based birth cohort of 15,645 individuals followed since 1991. AD was assessed
11 times between 6 months and 14 years old. Each time, mothers were asked if theirchild had an “itchy, dry skin rash in the joints and creases” and rated its severity as
no problem, mild, quite bad, or very bad. Using these responses, AD status was timeupdated and categorized as never, maybe, inactive, active-mild, or active-moderate/
severe at each timepoint. Cognition was assessed using the Griffiths Mental
Development Scales (GMDS) at age 1.5 years, the Wechsler Preschool and Primary
Scale of Intelligence (WPPSI) at 4 years, the Wechsler Intelligence Scale for Children(WISC) at 8 years, and the Wechsler Abbreviated Scale of Intelligence (WASI) at 15.5
years old. In cross-sectional analyses, linear regression was used to examine scoreswith respect to AD status, adjusted for sociodemographics, atopic comorbidities, andsleep. Across all 4 measures, we observed no significant associations between AD
status and IQ scores. However at 8 years old, WISC Performance IQ was slightly lower
among children with active-moderate/severe AD (β -2.16 [95% CI -4.12, -0.19]; p=0.03)
and WISC Verbal IQ was slightly higher among those with inactive AD (1.31 [0.28, 2.34];
p=0.01) compared to those without AD. Overall, we did not find any clear associations
between AD and general cognition during early childhood and adolescence. While ourresults suggest that select components of neurocognition such as nonverbal IQ may
be impacted by moderate-to-severe AD, our point estimates are within the standard
error of the WISC and such differences may be due to error. Future studies are needed
to discern the effects of AD on specific cognitive functions beyond IQ.

|

Late-Breaking ABSTRACTS

LB1678The association of IgA vasculitis and malignancy: A systematic review
M. Toker1, H. Ghersin1, U. Khanna2, R. Schwartz1, A. Kumthekar3, B. Wu2
Albert Einstein College of Medicine, Bronx, New York, United States, 2Dermatology,
Montefiore Medical Center, Bronx, New York, United States, 3Rheumatology, Montefiore
Medical Center, Bronx, New York, United States

1

Abstract Body IgA vasculitis (IgAV) is associated with malignancy in adult patients.
The clinical characteristics, temporal relationship, and underlying mechanisms ofmalignancy-associated IgAV are not well understood. Additionally, evidence-based
screening guidelines for occult malignancies in adults presenting with IgAV arelacking. We performed a systematic review of the English language literature acrossfive databases over the past 30 years, using PRISMA guidelines. Two independent
reviewers selected studies, extracted data, and determined study quality. Articles
met inclusion criteria if they contained information regarding IgAV and malignancy inadults older than 18 years. A total of 967 studies were screened and 93 articles were
included, comprising of 108 individual patient cases. The mean age of patients was
60.3±12.9 years, and the majority (65.7%) were male. Solid malignancy was morecommonly associated with IgAV than hematologic malignancy (67.7% vs 32.4%).
Malignancy preceded IgAV for most patients with solid cancer, whereas for most withhematological cancer, IgAV preceded malignancy or was diagnosed synchronously.
Patients with solid malignancies were more likely to exhibit systemic involvement of
IgAV, including renal, gastrointestinal, joint, and cutaneous symptoms, although thedifferences were not significant (p>0.05). The majority of patients with skin biopsy
had IgA deposition on DIF (71.2%), and the majority of those with reported IgA levels
had elevated serum IgA (71.8%). Based on the existing literature, we recommend
screening patients 50 years or older with new-onset or recurring IgAV for malignancy,
particularly solid organ cancer. Serum IgA levels might serve as a useful, non-invasive
screening test given that most patients with measured IgA levels had elevated serum
IgA. Prompt detection and treatment may improve prognosis and prevent long-term
consequences.

LB1680Effects of ganoderma lucidum extract and its active component, ganoderic acid A
on hair loss prevention
Y. Kwon1, J. Park1, H. Seol3, S. Lee3, G. G. Ryeom4, C. Heo2, S. Kang1
1
Cosmax, Seongnam, Gyeonggi-do, Korea (the Republic of), 2Seoul National
University Bundang Hospital, Seongnam, Korea (the Republic of), 3Hyundai Bioland,
Cheongju-si, Chungcheongbuk-do, Korea (the Republic of), 4Consortium of
Semiconductor Advanced Research, Seongnam, Gyeonggi-do, Korea (the Republic of)

Abstract Body Hair loss, also known as androgenetic alopecia, leads to the progressive
miniaturization of hair follicles and a reduction in the number of hair follicles in theanagen phase. While there are chemical products used to treat hair loss, their side
effects have recently emerged. Therefore, in this study, we investigated natural
products that alleviate hair loss. Ganoderma Lucidum (G. Lucidum), a traditional
oriental medicine, has been extensively studied for its effects on antioxidants,
regeneration, and anti-inflammation. In this study, we analyzed G. Lucidum and
Ganoderic acid A (GAA), the most abundant triterpenoid in G. Lucidum, to evaluate
hair loss prevention in vitro, ex vivo, and clinical tests. We found that G. Lucidum
extract and GAA both improved the proliferation of human dermal papilla cells(hDPCs) and human hair germinal matrix cells (HHGMCs). Also, G. Lucidum extractand GAA increased the expression of growth factors, such as VEGF and IGF-1 in eachhair cell. In addition, G. Lucidum extract and GAA showed hair follicle growth in lengthand diameter, compared to the control (vehicle) group in an ex vivo human scalpderived hair follicle culture model. Moreover, they both suppressed the progression
to the catagen phase of the hair growth cycle. Furthermore, clinical trials (24-week,
randomized, double-blind, controlled) demonstrate that G. Lucidum extract and GAA
applied to shampoo (leave off) and tonic (leave on) formulations have significant hairloss inhibition effects. Collectively, these results indicate that G. Lucidum extract andits active component, GAA, alleviate and delay the progression of alopecia, and they
could be used as an effective therapeutic for the treatment of hair loss.

16

Clinical Research – Epidemiology and Observational Research

LB1681

Risk of merkel cell carcinoma progression after treatment discontinuation inpatients with an objective response to anti-PD-(L)1 immunotherapy|

Late-Breaking ABSTRACTSLB1682

Association of inflammatory and pigmentary disorders with alcohol use disorderand psychiatric illness

L. Tachiki1, 2, Y. Moshiri Yi1, D. S. Hippe2, L. Zawacki1, E. Gong1, T. Pulliam1, K. Lachance1,
C. Church1, A. Fu1, A. J. Remington1, E. T. Huynh1, N. Harikrishnan1, M. Bierma1,
L. Zaba3, S. Bhatia1, 2, P. Nghiem1, 2
1
University of Washington, Seattle, Washington, United States, 2Fred Hutchinson Cancer
Center, Seattle, Washington, United States, 3Stanford University, Stanford, California,
United States

K. Kamal1, 2, D. H. Xiang1, K. Young1, A. Mostaghimi2, J. Barbieri2, J. M. Cohen3,
N. Theodosakis4
1
Harvard Medical School, Boston, Massachusetts, United States, 2Brigham and
Women's Hospital Department of Dermatology, Boston, Massachusetts, United States,
3
Yale School of Medicine, New Haven, Connecticut, United States, 4Massachusetts
General Hospital, Boston, Massachusetts, United States

Abstract Body Immunotherapies (IMTX) with anti-PD-(L)1 antibodies are the preferredfirst-line treatment in most patients (pts) with advanced Merkel cell carcinoma (MCC)and are associated with a high (~50%) objective response rate. Optimal duration oftreatment (DoT) in pts responding to IMTX is unclear. We conducted this retrospective
study to evaluate rates of progressive disease after IMTX discontinuation (DC) in 105
pts with advanced MCC who had an objective response (partial response [PR]: 29,complete response [CR]: 76) to first-line IMTX. Median follow-up in this cohort was 34
months from IMTX initiation. Among the 105 pts, 58 had discontinued IMTX (median
DoT: 12.0 months) and 47 were continuing (median DoT: 17.8 months) at data
cutoff. Reasons for DC were classified as elective (N=30) or due to toxicity (N=28).
Progression-free fraction (PFF) for the entire cohort was 75% at 2 years. The 2-year
PFF was 63% in pts who discontinued IMTX and 80% in pts who continued IMTX, HR =2.25, p=0.059. Among pts without toxicity, the 2-year PFF remained numerically higher
in those who continued IMTX (80%) compared to elective DC (69%), HR 1.30, p=0.62.
Pts treated for ≥18 months had improved PFF rates compared to those treated for
12 or 6 months, HR per additional 6-month interval = 0.95, p = 0.043. Among pts
who discontinued IMTX, those with PR had a numerically higher rate of progression
compared to pts with CR (progression rate 2 years after DC: 56% vs. 29%; HR 1.74, p= 0.22). These data suggest that extended DoT may be associated with better MCC
outcomes in responding pts. Further studies evaluating innovative approaches toextend DoT such as reduced frequency dosing schedules are indicated.

Abstract Body While depression and anxiety (psychiatric disease, PD) have been
separately associated with skin disease (SD) and alcohol use disorder (AUD), theinteraction between PD, SD, and AUD, has not yet been explored. We explore thisquestion in a matched case-control study of the United States All of Us Research
program (5/2018-1/2023). Adults with atopic dermatitis (AD), acne or rosacea,
alopecia areata (AA), hidradenitis suppurativa (HS), psoriasis, and pigmentary
disorders (vitiligo, melasma, and post-inflammatory hyperpigmentation), wereidentified using International Classification of Diseases codes. Multivariate logistic
regression was used to evaluate the odds of AUD among those with SD alone, SD
and PD, and PD disease alone. Mediation analysis was performed to evaluate the roleof PD on this relationship. We identified 65,676 total patients with SDs. There wasa significant association between AUD and AD (OR 1.58 [1.39-1.79]), acne/rosacea(1.33 [1.18-1.51]), HS (1.91 [1.38-2.66]), psoriasis (1.80 [1.50-2.15]), and pigmentary
disorders (1.37 [1.24-1.52]) (p<0.001). When comparing patients with both SD andcomorbid PD versus patients with PD only, there was a significant association with
AUD for patients with AD (1.27 [1.14-1.41]), acne/rosacea (1.21 [1.09-1.34]), AA (1.91[1.21-2.99]), and psoriasis, (1.32 [1.13-1.53]) (p <0.01), but pigmentary disorders andHS lost significance. Mediation analyses demonstrated that PD was a significant
mediator for AUD across all SDs, accounting for approximately 50-80% of the total
AUD risk, except HS, for which PD accounted for 31% of total AUD risk. Overall, SD is
associated with increased odds of AUD, which is partially mediated by anxiety anddepression. These findings highlight the profound psychological and physical healtheffects of CSD and suggests a potential role for screening for alcohol use disorders
in these patients.

LB1683

LB1684Skin cancer risk in BRCA1/2 mutation carriers
L. Navsaria, A. Haas, J. Corredor, B. Arun, S. Giordano, K. Nead, M. Wehner
The University of Texas MD Anderson Cancer Center, Houston, Texas, United States

Abstract Body BRCA mutation carriers have a well-documented risk of breast, ovarian,
prostate, and pancreatic cancer. Studies evaluating the association between BRCA
mutations and skin cancer have produced inconsistent results and have limitations,particularly potential surveillance biases. We aimed to investigate skin cancers in
BRCA mutation carriers using claims data. We performed a retrospective cohort study
using a deidentified Optum claims dataset of more than 7 million patients (20072022). We included patients who had received BRCA testing, identified by CPT codes.
Positive BRCA results were identified by at least one ICD code for genetic susceptibility
to breast or ovarian cancer (Z15.01, Z15.02, V84.01, V84.02) entered in the 3 months
prior or up to 3 years after the BRCA test date. Skin cancer outcomes were identified
using ICD codes plus CPT codes for treatment procedures for basal cell carcinoma(BCC), squamous cell carcinoma (SCC), and melanoma. We performed a competingrisks regression (competing risk of death) comparing patients with evidence of
positive BRCA tests to those without, adjusted for age, gender, race, census region,
history of skin cancer, and history of actinic keratosis. We identified 71092 patients
who were tested for BRCA and met inclusion criteria. Mean age was 49.1 (SD 14.7)
and 90.3 % were female. The mean follow-up time after BRCA test date was 3.2 years(SD 2.1 years). Evidence of a positive BRCA test was associated with a HR of 1.19
(95% CI 1.06 – 1.34) for skin cancer overall in adjusted competing risks regression.
When sub-divided by cancer type, evidence of positive BRCA test was associatedwith a HR of 1.42 (95% CI 1.02-1.97) for melanoma and a HR of 1.18 (95% CI 1.041.33) for keratinocyte carcinoma (BCC or SCC). Our study supports an association
between BRCA mutations and skin cancer, with surveillance bias reduced, though not
fully eliminated. Improved evidence for the association between BRCA mutations andskin cancer outcomes could aid in establishing specific, complete cancer screening
recommendations to patients with BRCA mutations.

Investigating the drug survival of long-term immunomodulating medications forbullous pemphigoid in an American center
Z. Awethe, M. Viveiros, J. Kaffenberger
College of Medicine, The Ohio State University, Columbus, Ohio, United States

Abstract Body There is a paucity of data on prescribing patterns and drug survival forbullous pemphigoid (BP). Delineation of such practices can help build a framework
for more effective BP management. This is a retrospective study of BP patients todetermine the long term-efficacy and drug survival of long-term immunomodulating
systemic medications used to treat the disease. A total of 104 BP patient’s aged
18 and older from 2015-2021 at The Ohio State University were categorized bytreatment plans and survival was analyzed by Kaplan-Meier survival curves. A totalof 117 treatments were included and median drug survival time was observed forazathioprine (2195.5 [AZI1] days; 95% CI 8-2221), methotrexate (1168 days; 98% Cl
328-2221), dapsone (953 days; 98% CI 166-2557), mycophenolate mofetil (620 days;
95% CI 93-1421), rituximab (602 days; 95% CI 243–973), and doxycycline (266 days,
95% CI 116-451) (log-rank p= 0.0001). For 12 out of 17 total rituximab treatment end
dates were determined by the dates of the study pull, 2 treatments were determinedby patient death[KJ2] (septic shock and metastatic lung cancer), and 3 by the startof a new treatment. The rituximab data was the most heavily censored by pull dateso may impact results. Compared to azathioprine, doxycycline (adjusted hazard
ratio 3.67; 95% CI 1.66-8.08; p=0.0013), mycophenolate mofetil (adjusted hazard
ratio 2.64; 95% CI 1.12-6.21; p=0.027), and rituximab (adjusted hazard ratio 3.17;
95% CI 1.32-7.63; p=0.0099) were associated with a significantly increased risk ofdrug discontinuation. To conclude, azathioprine and methotrexate demonstrated
a higher drug survival whereas doxycycline, mycophenolate mofetil, and rituximab
demonstrated a lower drug survival in patients with bullous pemphigoid. Thisdata allows clinicians to make more informed decisions on prescribing long-term
immunomodulating medications when treating BP and subsequently reduce the useof corticosteroids, normally used for BP, and its associated side effect burden.

17

Clinical Research – Epidemiology and Observational Research

LB1685

Deciphering sensitization patterns in atopic dermatitis patients with atopic
comorbidities
Y. Fang1, 2, 3, C. Clemens3, M. Möhrenschlager1, P. Schmid-Grendelmeier3,
M. Brüggen1, 2, 3
1
Dermatology, Hochgebirgsklinik Davos AG, Davos-Wolfgang, GR, Switzerland,
2
CK-CARE AG, Davos Wolfgang, GR, Switzerland, 3Allergy Unit, UniversitatsSpital Zurich
Dermatologische Klinik, Zurich, ZH, Switzerland

Abstract Body Atopic dermatitis (AD) patients have an increased risk to develop
atopic comorbidities such as food allergies, allergic asthma or rhinoconjunctivitis. It ishypothesized that epidermal dysfunction in AD paves the way to develop sensitization(i.e. specific IgEs) against certain allergens and thereby contributes to the developmentof immediate-type allergies. In this study, we aim at specifying sensitization patterns
against airborne and food allergens of patients suffering from different atopic
diseases (Food allergies, allergic asthma, allergic rhinoconjunctivitis) with or without
concurrent AD. We thereby sought to understand, whether AD patients may develop
different sensitizations against a different spectrum of allergens, which in turn could
point towards distinct pathways of sensitization. We performed a monocentric,
retrospective observational study at the University Hospital Zurich. A total of 950
Patients with AD (134), food allergies (172), allergic asthma or rhinoconjunctivitis(240) treated between 2015 and 2022 were included. Clinical characteristics andresults from multiplex IgE testing (ISAC) were analyzed and correlated. AD patients
had overall higher sIgE levels and broader allergen sensitization. Patients sufferingfrom food allergy and AD showed, in comparison to food allergy patients without
AD, unique sensitization patterns against food allergens, a.o. meat allergens suchas bos d5 or gad c1. In contrast, asthma / allergic rhinoconjunctivitis patients withand without AD exhibited similar sensitization patterns against aeroallergens. In
conclusion, our findings of distinct food- but not airborne-allergen sensitization in AD
patients support the hypothesis that epicutaneous sensitization contributes to foodallergy development, but not respiratory allergies.

LB1687

Impact of climate change on atopic dermatitis: A systematic search and review by
the International Eczema Council
S. Wang1, N. Stefanovic2, R. L. Orfali3, V. Aoki3, S. Brown4, S. Dhar5, L. F. Eichenfield6,
C. Flohr7, A. Ha1, C. Mora8, J. Murase1, M. Rosenbach9, J. Thyssen10, M. L. Wei1,
A. D. Irvine11, K. Abuabara1
1
University of California San Francisco, San Francisco, California, United States, 2The
University of Dublin Trinity College, Dublin, Ireland, 3Universidade de Sao Paulo, Sao
Paulo, São Paulo, Brazil, 4University of Edinburgh, Edinburgh, United Kingdom, 5Instituteof Child Health, Kolkata, India, 6University of California San Diego, La Jolla, California,
United States, 7King's College London, London, United Kingdom, 8University of Hawai'iat Manoa, Honolulu, Hawaii, United States, 9University of Pennsylvania, Philadelphia,
Pennsylvania, United States, 10University of Copenhagen, Copenhagen, Denmark,11
Children's Health Ireland at Crumlin, Crumlin, Dublin, Ireland
Abstract Body Atopic dermatitis is known to be influenced by environmental factors;
however, the impact of climate change remains poorly quantified. We conducted asystematic search on the impact of ten climatic hazards sensitive to greenhouse gas
emissions on atopic dermatitis and identified 17 studies that were primarily locatedin the US, Europe, Asia, and Africa. All climatic hazards studied had theoretical or
empirical evidence for aggravation of atopic dermatitis, whereas there was minimal
evidence for improvement of atopic dermatitis. The impact on atopic dermatitis wasboth through direct effects such as stimulation of inflammation from particulatematter from wildfires, and from indirect effects such as drought-induced migrationand poverty. To illustrate the impact of climatic hazards, we created maps comparing
the past, present, and projected future impact of climatic hazards to global atopic
dermatitis prevalence data. Additional studies addressing the impact of multiple
environmental risk factors are needed to address gaps in understanding and to
inform policy in areas where atopic dermatitis continues to rise in prevalence.

|

Late-Breaking ABSTRACTSLB1686

Impact of dupilumab on survival in patients treated with immune checkpoint
inhibitors
B. W. Leung1, 2, 3, S. Zhang1, H. Rashdan1, G. Wan1, N. Nguyen1, N. LeBoeuf2, 3, 4,
Y. Semenov1, 41
Massachusetts General Hospital, Boston, Massachusetts, United States, 2Brigham
and Women's Hospital, Boston, Massachusetts, United States, 3Dana Farber Cancer
Institute, dana farber, Boston, Massachusetts, United States, 4Harvard Medical School,
Boston, Massachusetts, United States

Abstract Body Cutaneous immune-related adverse events (cirAEs) are the mostcommon toxicities to occur in the setting of immune checkpoint inhibitor (ICI)
therapy. Conventional treatments for cirAEs include topical and systemic steroids,
and, less commonly, biologics. There is growing interest in understanding the impactof immunomodulating medications, including dupilumab, on clinical outcomes for
ICI patients. Using data from Mass General Brigham, we identified 33 patients who
received dupilumab after starting ICI treatment. Cohorts were propensity scorematched on age, sex, race/ethnicity, and ICI type. The time-varying multivariable Cox
proportional hazards model was adjusted for ICI cycle, cirAE status, organ system,
tissue type, systemic steroid use, and cancer stage. Among the study group, 82%of patients started dupilumab for treatment of their cirAEs, while 12% of patientswere treated with dupilumab for flare of their pre-existing dermatoses after starting
ICI. 6% of patients were treated with dupilumab for their asthma. The most common
rash morphologies were eczematous (42%) and bullous (29%), followed by lichenoid(10%), psoriasiform (10%), isolated pruritus (6%), morbilliform (3%), morphea (3%),
and sclerodermoid (3%). 74% of patients had significant improvement with dupilumab,
while 10% had partial improvement. Multivariate modeling demonstrated thatreceiving dupilumab had no significant impact on survival for patients who received
ICI (HR = 1.01, p-value > 0.9). Given the significant improvement in symptoms andlack of adverse impact on survival, there is evidence to support the use of dupilumab
in patients experiencing cirAEs. Furthermore, this can likely allow patients to stay on
ICI therapy for longer, optimize quality of life, and reduce the likelihood of treatment
discontinuation due to cirAEs.

LB1688Uncombable hair syndrome and atypical clonal nevus presentation in a VACTERL
syndrome patient
P. L. Smith, S. Shalin, M. Evans
Dermatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas,
United States

Abstract Body A 7-year-old Caucasian girl was referred to dermatology for evaluationof a mole on the back with recent onset of irregular pigmentation. Past medical
history was significant for VACTERL syndrome with associated cardiac, GU, andnervous system anomalies. Physical examination revealed a 5 mm light brownmacule on the upper back with two distinct black foci, one located centrally and theother located eccentrically. A shave biopsy of the nevus was performed, revealinga proliferation of junctional and intradermal melanocytic nests. The cells lacked
pigment superficially but demonstrated deeper extension of epithelioid melanocyteswith dense cytoplasmic melanin and multiple melanophages. Cytologic atypia andmitoses were absent. The patient received a diagnosis of an inverted type A nevus(clonal nevus) and reassurance. The patient was also incidentally noted to have unruly
blonde hair which would not lay flat. A hair clipping was sent to dermatopathology for
microscopic examination. The hairs were embedded in paraffin and cut across theshort axis, revealing irregular cross-sections consisting of reniform and triangularshapes. Genetic testing identified two pathogenic variants in the PADI3 gene,consistent with autosomal recessive PADI3-related uncombable hair syndrome.
The coexistence of a clonal nevus and uncombable hair syndrome is a previously
undescribed presentation. Furthermore, two distinct foci of hyperpigmentation within
the patient's nevus are also unusual, as clonal nevi typically present with a single
eccentric or central focus of blue-black or blue-gray pigmentation.

18

Clinical Research – Epidemiology and Observational Research

LB1689Predictors of mortality in DRESS-associated myocarditis: A systemiatic review
C. Samuel, M. Fazal, P. Reddy, S. Rozati, J. Kang
Dermatology, Johns Hopkins University, Baltimore, Maryland, United States

Abstract Body Drug reaction with eosinophilia and systemic symptoms (DRESS)
syndrome with cardiac sequela is an uncommon diagnosis that portends a poor
prognosis. We conducted a systematic review using PRISMA guidelines on
DRESS-related myocarditis and included an additional case from Johns Hopkins
to characterize the clinical and demographic factors associated with increased
mortality. Our study included a total of 90 patients (mean +SD age, 37.8±19.2; 54.0%
female), representing the largest cohort to date. Multivariate logistic regression
was performed to determine factors associated with mortality. The mortality rate
was 30% in patients with DRESS-related myocarditis. The most common culprit
medications were minocycline (15.6%), sulfasalazine (10.0%), and allopurinol (8.9%).
The median time (IQR) to onset of myocarditis after the initial DRESS diagnosis in
weeks was 1.4 (0-3.6) for non-fatal cases and 4 (2-8) for fatal cases (p=0.007). Eachweek spent between the date of DRESS diagnosis and onset of cardiac symptoms
was associated with a 10% increase in the odds of mortality (OR 1.103, 95% CI [1.0101.205], p= 0.029) when adjusting for age and sex. Steroid use was associated with
88% decreased odds of mortality (OR 0.119, 95% CI [0.0176-0.801], p=0.029) when
adjusting for age and sex. Race was reported for 36 patients (40%), with Asian being
the most common (17.8%) followed by African American (10.0%), Caucasian (8.9%)
and Hispanic (3.3%). An Asian background was associated with allopurinol-induced
DRESS with myocarditis (p=0.015). An African American background was associatedwith sulfonamide-induced DRESS with myocarditis (p=0.005). Our study highlightsthat delayed onset of myocarditis may be an independent predictor of mortality,
underscoring the need for an extended follow-up of patients diagnosed with DRESS toassess signs of a late cardiac injury. Our results further support the use of steroids asa life-saving treatment of DRESS. Finally, minocycline, sulfasalazine, and allopurinol
may be associated with an increased risk of DRESS associated myocarditis.

LB1691

The relationship of age and body mass index with immunotherapy response inmerkel cell carcinoma: Analysis of 183 patients
R. Alam, X. Fan, D. S. Hippe, E. T. Huynh, E. Gong, S. Park, P. Nghiem
University of Washington, Seattle, Washington, United States

Abstract Body Merkel cell carcinoma (MCC) is an aggressive skin cancer with a highrisk of metastasis. Development of anti-PD-1/PD-L1 immunotherapy (IMTX) has
significantly improved outcomes for advanced MCC. Currently, ~50% of patients
have durable benefit from IMTX. It is important to identify factors that influence IMTX
response. Studies of several cancer types (melanoma, renal cell, and non-smallcell lung cancer) have demonstrated an association between older age or higher
BMI with improved IMTX response and overall survival (OS). In this retrospective
analysis from a single-center registry, we explored the effects of age, BMI, and ECOG
performance status on IMTX response in 183 patients. All patients received first-line
IMTX with a median follow-up of 882 days. Clinical features, including age and BMI,
were collected at IMTX initiation. Treatment response, disease progression, and OS
were analyzed using Cox regression with non-linear relationships estimated using
natural cubic splines. For each outcome, age, sex, stage, immunosuppressed status,
BMI and ECOG performance status were all included in the model. Based on resultsfrom multivariate models, BMI was not significantly correlated with OS (p=0.680),
objective response (p=0.297), or disease progression (p=0.664). Age had a nonlinear relationship with response (p=0.015), where patients near the median age of
70 were more likely to respond than younger or older patients. Older age was not
significantly linked to OS (p=0.333) or disease progression (p=0.09), but ECOG score>1 was associated with significantly lower OS (HR=3.01 [1.29-6.99], p=0.01) Somelimitations of this analysis include its retrospective nature and single-institution
experience, although the cohort size was significant for a rare cancer. While priorstudies in other cancers have shown obesity and advanced age are associated with
better IMTX response, these trends were not observed in this cohort of MCC patients.

|

Late-Breaking ABSTRACTSLB1690Definitive radiotherapy for initial management of merkel cell carcinoma: Assessing
a novel hypo-fractionated regimen
A. Menon, E. T. Huynh, P. H. Goff, K. Lachance, M. H. Nguyen, J. Iyer, K. Nagase, K.
Parvathaneni, P. Nghiem, U. Parvathaneni
University of Washington, Seattle, Washington, United States

Abstract Body Merkel cell carcinoma (MCC) is a rare skin cancer. Standard therapy
often includes surgery and post-operative radiation (PORT). Given the radiosensitivityof MCC, definitive radiotherapy (RT) may be effective when surgery is contraindicated
due to morbidity, functional compromise, and/or delayed wound healing. Here we
retrospectively analyzed the efficacy of definitive RT for patients (pts) who received
hypo-fractionated RT (hRT; 8 Gy x 1-3 fractions) versus conventional RT (cRT; 1.8-2 Gy
x 25-35 fractions). We also compared the efficacy of definitive RT to surgery + PORT.
From the Seattle MCC registry, we identified 61 Stage I-III pts who received definitive
RT without upfront surgery or systemic therapy and a comparison cohort of 922 pts
who received surgery + PORT. Of 61 pts who received definitive RT, 20 received hRT(median 24 Gy, range 8-24 Gy) and 41 received cRT (median 60 Gy, range 50-70 Gy).
With 2.9 years (range 0.25-15) of median follow-up for cRT and 1.3 years (range 0.13) for hRT, only 5 of 61 (8%) pts who received definitive RT recurred loco-regionallywithin the RT field (local, in-transit or nodal recurrences). Among 41 cRT pts, 2 hadlocal recurrences and 1 had an in-transit recurrence. Of 20 hRT pts, 1 recurred locallyand 1 regionally. Both regimens had a 95% in-field local control rate (39/41 cRT;
19/20 hRT), compared to 96% for combined treatment (885/922). Disease-specificsurvival was comparable among pts who received definitive RT (68%) versus surgery+ PORT (73%). These findings suggest that hRT and cRT appear similar in efficacy.
Use of hRT may offer a less toxic, more convenient alternative to cRT and warrants
further exploration. Furthermore, definitive RT seemed effective in treating MCC anddoes not appear to compromise local control compared to surgery + PORT and may
be an option when surgery is contraindicated.

LB1692A new method to assess the efficacy of biologics for psoriasis
E. Toichi, S. Yonekura, K. Takamoto, K. Tsujihana
Dermatology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

Abstract Body Nowadays, biologics are so effective that about half of the patientswith psoriasis are able to achieve Psoriasis Area and Severity Index (PASI) 100. In
real-world practice, the dosing interval is sometimes extended in patients who has
achieved near or complete clearance of the skin. If biologics are administered at 12,16- or even 24-week intervals to maintain clear skin, all results are described as PASI
100, although the efficacy of these cases is not likely to be the same. We attempted
to establish a new method to evaluate the efficacy of biologics with not only the
improvement of skin lesions, but also with dosing intervals. We named it efficacy
PASI (EPASI) and defined it as follows. EPASI = improvement of PASI multiplying by
one plus the numerics calculated from the dosing. The numerics were calculated
this way. The regular dosing interval was subtracted from the actual dosing intervaland divided by the regular dosing interval and then multiplied by the coefficient foreach biologic. Using EPASI, we analyzed our patients treated with ustekinumab for
11 years at longest. The EPASI has numerical values above 100. Some of the highresponding patients’ EPASI gradually went up during use of ustekinumab for several
years. This results shows that these patients has not only maintained the clearanceof the skin, but also has been in remission state less likely to relapse. Moreover, thisnew method allows us to distinguish super-responders from high-responders forfurther analysis.

19

Clinical Research – Epidemiology and Observational Research|Late-Breaking ABSTRACTSLB1693

LB1694

S. Kobayashi1, A. Osada2
Dermatology, Seibo International Catholic Hospital, Tokyo, Japan, 2Dermatology,
Nishitokyo Central General Hospital, Tokyo, JapanJ. W. Gotschall, R. Fitzsimmons, D. B. Shin, J. Takeshita
Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia,
Pennsylvania, United States

Abstract Body Palmoplantar pustulosis (PPP) is a chronic pustular dermatitis
involving the palms and soles. About 30% of PPP cases associates osteoarthritis. It
is known that 70-80% of Japanese PPP are triggered by focal infection such as apicalor marginal periodontitis, asymptomatic tonsilitis or sinusitis, and are considered as
the Andrews type. For their treatment, dental treatment, tonsillectomy or antibiotics
for sinusitis should prefer to symptomatic treatments such as phototherapy,
biologics and DMARDs. A characteristic feather of Andrews type is that the earlylesions are vesicles. On the other hand, in Western countries, Barber type associatedwith plaque psoriasis on the extremities with sterile pustules on the palms and soles
is the mainstream, and is considered to be a local type of pustular psoriasis. And fortheir treatment, the conventional therapies for psoriasis are used. However, it has
been pointed out that there are cases triggering a focal infection also in Barber typeof PPP, and there is an opinion that the two types cannot be clearly distinguished.
We experienced a suspected Barber type of PPP in Japanese. Furthermore, there aresome cases which seem to be an intermediate type of the two in consideration ofpathological and clinical findings. As biologics are used for treatment in refractory
cases also in Andrews type of PPP, the significance and the clues to distinguish thetwo was reconsidered. In some Japanese patients with PPP, dental lesions became
apparent during the administration of biologics. Paradoxical reactions were also
observed in some of such cases due to exacerbation of focal infection. Although a
global collaborative study is needed to compare the treatment responses precisely,
we consider that these two should be distinguish from the perspective of therapeutic
approaches.

Abstract Body Atopic dermatitis (AD) is more severe among Black children comparedto White children in the United States (U.S.). However, it is unclear what and how
much social and environmental factors drive this health disparity. To identify thesocial and environmental factors that contribute to racial disparities in pediatric AD
severity, we performed a cross-sectional analysis of enrollment data from children in
the Pediatric Eczema Elective Registry, air pollution data from the U.S. Environmental
Protection Agency, and social determinants of health data from the American
Community Survey. The primary outcome was AD control (good [reference] vs. poor).
Covariates included self-reported race/ethnicity, other individual sociodemographic
and zip code-level neighborhood characteristics, and zip code-level air pollution
measures. Multivariable logistic regression was used to evaluate the associations
between covariates and AD control. The study included 3,480 children (52.8% Female;
28.3% White; 60.9% Black; 3.0% Asian; 7.4% Hispanic). In unadjusted analyses, Blackchildren had higher odds of poor disease control compared to White children (oddsratio [OR] 1.47; 95% confidence interval [CI] 1.26-1.71). Adjusting for particulatematter (PM) 2.5, PM10, ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2),and carbon monoxide (CO) exposure together attenuated the association between
Black race and AD control (OR 1.31; 95% CI 1.10-1.56). Additional adjustment forsocial context further attenuated this association (OR 1.24; 95% CI 0.99-1.55). In
these multivariable models, higher levels of PM10 (OR 1.83; 95% CI 1.48-2.27), PM2.5(1.93; 95% CI 1.35-2.77), and SO2 (OR 2.42; 95% CI 1.18-4.99) exposure were eachindividually associated with poorer disease control. Our findings provide evidence
that social and environmental factors, including air pollution exposure, contribute toracial disparities in pediatric AD severity in the U.S. and highlight potential targets forinterventions to achieve health equity.

LB1695

LB1696

Investigation on the significance of distinguishing Andrews type and Barber typeof PPP

1

Social and environmental context impacts racial disparities in pediatric atopic
dermatitis severity in the Unites States

Racial disparities in steven-johnson syndrome and toxic epidermal necrolysis
clinical outcomes

The characteristics and inheriting pattern of skin aging in Chinese women: An
intergenerational study

D. Garate1, C. J. Thang1, I. Flores2, D. Thomas1, G. Golovko3
1
The University of Texas Medical Branch at Galveston School of Medicine, Galveston,
Texas, United States, 2Sam Houston State University College of Osteopathic Medicine,
Conroe, Texas, United States, 3Pharmacology, The University of Texas Medical Branch
at Galveston, Galveston, Texas, United States

Y. Zhao
Dermatology, Beijing Tsinghua Changgung Hospital, Beijing, China

Abstract Body Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis(TEN) are potentially life-threatening, immune-mediated skin disorders that
commonly present with the sloughing of skin and mucous membranes. Although priorstudies have investigated the clinical outcomes of SJS/TEN, no study has examined
the relationship between race and clinical outcomes. This study aims to elucidate
the associations between race and SJS/TEN clinical outcomes. We conducted aretrospective cohort analysis of patients from the US Collaborative Network subsetof the TriNetX database. Using validated ICD-10 codes the population was stratified
to compare clinical outcomes between Black and African American patients toWhite non-Hispanic patients following the onset of SJS or TEN. A 1:1 propensity
score match analysis (PSM) was conducted adjusting for age at index event anddemographics. Adjusted Risk Ratios (aRR) with 95% CI (p<0.05) were utilized toassess 45-day clinical outcomes. The balanced patient cohorts identified 2,278
patients per cohort. We found that Black and African American patients experiencea greater risk of new-onset primary hypertension (aRR [95% CI]) = (1.49 [1.02-2.17]),heart failure (2.29 [1.35-3.86]), volume depletion (2.14 [1.38-3.33]), acute kidney
failure (2.39 [1.54-3.70]), pulmonary collapse (1.67 [1.29-2.16]), acute respiratory
failure (2.01 [1.56-2.60]), sepsis (2.34 [1.87-2.92]), and mortality (1.62 [1.22-2.14]).
There were no significant risk ratios for the outcomes related to pneumonia, ICU
admission, and volume depletion. These results suggest that Black and African
American patients may be at an increased risk for adverse clinical outcomes
following SJS/TEN compared to White non-Hispanic patients. In conclusion, thisstudy emphasizes the need for further research into the influence of ethnicity andrace on SJS/TEN outcomes.

Abstract Body Objective: The features of aging skin vary among populations, and its
inheriting patterns for a specific population remains to be elucidated. In this study, we
aimed to investigate the aging features of Chinese women and explore the inheriting
patterns of skin aging between mothers and daughters. Methods: 87 female
subjects aged 30-80 were recruited and analyzed, including 40 pairs of mother anddaughter. We assessed the subjects' perceived age and graded the aging traits of thesubjects using a modified skin aging assessment scale. Statistical methods wereused to analyze the trends of the aging characteristics and the difference between
the perceived age groups. By introducing the similarity parameter, we comparedwhether various skin aging characteristics have similar patterns between mothersand daughters. Results: We discovered that rhytides, laxity, dyschromia, and benign
skin tumors became more prevalent during the aging process of Chinese women.
The score of dyschromia showed rapid increase before the age of 50 and changed
slower after the age of 50, while skin laxity and rhytides significantly increased after
the age of 43. We also found that the patterns of skin aging were similar between
mother-daughter pairs. Conclusions: Our study systematically characterized the
predominant skin aging features of Asian female population and first verified thesimilarities of skin aging predisposition between mother and daughter. Which might
benefit precision treatment or prevention for skin aging.

20

Clinical Research - Interventional Research

LB1697

Individual SALT score trajectories of de novo patients with alopecia areata (AA)treated with ritlecitinib in the ongoing phase 3, long-term, open-label ALLEGRO-LT
study
B. King1, P. Mirmirani2, K. Lo Sicco3, Y. Ramot4, 5, R. Sinclair6, R. Edwards7, U. Kerkmann8,
D. Wajsbrot9, S. Zwillich10, A. Lejeune11
1
Yale School of Medicine, New Haven, Connecticut, United States, 2The Permanente
Medical Group, Vallejo, California, United States, 3New York University Grossman Schoolof Medicine, New York, New York, United States, 4Hadassah Medical Center, Jerusalem,
Israel, 5Hebrew University of Jerusalem, Jerusalem, Israel, 6Sinclair Dermatology,
Melbourne, Victoria, Australia, 7Health Services Consulting Corporation, Boxborough,Massachusetts, United States, 8Pfizer Pharma GmbH, Berlin, Berlin, Germany, 9Pfizer
Inc, New York, New York, United States, 10Pfizer Global Research and Development,
Groton, Connecticut, United States, 11Pfizer Inc, Paris, France

Abstract Body This post-hoc analysis of the ongoing phase 3 ALLEGRO-LT study(NCT04006457) evaluated Severity of Alopecia Tool (SALT) score trajectories in
ritlecitinib-treated patients with AA. Analysis included ritlecitinib-treated de novo
patients enrolled in ALLEGRO-LT who had not received treatment in other ALLEGRO
studies (N=447). Patients aged ≥12 years with AA and ≥25% scalp hair loss received
ritlecitinib 200 mg once-daily (QD) for 4 weeks (loading dose), followed by 50
mg QD. SALT score trajectories were assessed up to Week (W) 96. Patients werecategorized as responders, partial responders, non-responders, or relapsers, basedon three periods (early [Baseline-W24], middle [W24-W48], and late [W48-W96]),
achieving SALT score ≤20 response (responders), or 30% SALT score improvementfrom baseline (partial responders). Multivariable logistic regression was used toassess the impact of demographics and disease characteristics on response. SALT
score trajectories showed that 275 (61.5%) patients were responders (early: n=98
[44.3%]; middle: n=51 [11.4%]; late: n=26 [5.8%]), 53 (11.9%) partial responders, 98(21.9%) non-responders, and 21 (4.7%) relapsers. Sex (female), SALT score <100, andshorter episode/disease duration were associated with treatment response. Over
60% of ritlecitinib-treated patients were SALT score responders, most of whom had
an early response. Analysis of individual response profiles may help identify patientand disease characteristics associated with treatment response.

LB1699Assessment of selected biochemical and immunological parameters after treatment
by cosmetic procedures
S. M. Aladwan1, 2
Dermatology, American Academy of Dermatology, Des Plaines, Illinois, United States,2
Medical Center, The George Washington University, Washington, District of Columbia,
United States|

Late-Breaking ABSTRACTSLB1698Phase 2 study of the safety and efficacy of QTORIN rapamycin in the treatment of
microcystic lymphatic malformations
J. M. Teng1, J. Martini2, J. Treat4, J. Connor3, A. Small5, T. Funk5, M. Waner6
Stanford University School of Medicine, Stanford, California, United States, 2Palvella
Therapeutics, Wayne, Pennsylvania, United States, 3Confluence Statistics, Coral
Gabels, Florida, United States, 4The Children's Hospital of Philadelphia, Philadelphia,
Pennsylvania, United States, 5Oregon Health & Science University, Portland, Oregon,
United States, 6Vascular Birthmark Institute, New York, New York, United States
1

Abstract Body Introduction: Microcystic LM is a serious, rare, and chronic diseasecharacterized by lymphorrhea, acute cellulitis, and significant patient morbidity.
Treatment options are limited with no FDA approved therapies. QTORIN 3.9%
rapamycin anhydrous gel was granted FDA Fast Track Designation for treatment ofMicrocystic LM. We completed a Ph. 2 study of QTORIN rapamycin in microcystic LM.
Methods: The Ph. 2 study was open-label where all subjects (n=12), aged ≥6 years
old with at least moderate disease severity received 12-weeks of topical QTORIN
rapamycin treatment once daily, with efficacy assessments at 12-weeks comparing
to baseline control. Results: The Ph. 2 study demonstrated statistically significant
and clinically meaningful improvements for all patients treated with QTORIN
rapamycin. Two pre-specified efficacy endpoints were the clinician global impressionof change (CGI-C) and patient global impression of change (PGI-C). All 12 pediatricand adult patients in the study were either “much improved” or “very much improved”
on the CGI-C (p<0.0001), and all twelve patients improved on the PGI-C (p<0.0001).
In addition, these patients demonstrated statistically significant improvementson the key clinical manifestations including hyperkeratosis, erythema, height, andlymphorrhea. Safety profile was similar to previous clinical trials with QTORIN
rapamycin. Systemic levels of rapamycin remained below the limit of detection ina certified clinical lab for all patients at all timepoints. Conclusions: 12-weeks oftargeted, topical treatment with QTORIN rapamycin resulted in significant clinicalbenefit for patients with cutaneous manifestation of microcystic LM. Based on thestatistically significant and clinically meaningful results, a Ph.3 placebo-controlled
study is currently being planned.

LB1700SYK antagonism in hidradenitis suppurativa demonstrates clinical efficacy withgrearter response in B-cell predominant disease: Results of a open-label, proof-ofconcpet phase 2 clinical trial

1

R. Jepsen1, A. Flora1, 2, E. Kozera1, J. W. Frew1, 2
1
Ingham Institute, Liverpool, New South Wales, Australia, 2University of New South
Wales, Sydney, New South Wales, Australia

Abstract Body Background: The use of non-invasive cosmetic procedures suchas Botulinum toxin and hyaluronic acid filler (HA) are commonly used in cosmetic
and therapeutic. However, BOTOX therapy is generally considered safe and without
significant adverse effects. However, these treatments' impacts must be understoodand investigated thoroughly. The objective of this prospective study was to evaluate
the impact of using injections of hyaluronic acid filler (HA) and BOTOX on somehuman biochemical parameters, CBC, and inflammatory markers. Methods: Eightyfive subjects who have undergone BOTOX and/or HA injections were recruited.
Samples of study and control groups were collected into EDTA for CBC and serum
tubes for the analysis of the rest of the parameters. Results: Our results revealed
that using BOTOX and HA filler has no significant effect on ALT, AST, GGT, and CK-MB
levels (p-value > 0.05). While there was a decrease in ALP level in subjects injectedwith both BOTOX and HA filler. Moreover, we discovered that two of our study groups
had significantly higher serum LDH levels than the control group. CRP, TNF-α, and IL17 were elevated in the study group compared with the control group. However, thisdifference was statistically insignificant (p-value > 0.05). Conclusion: Accordingly,
using BOTOX and HA filler may result in mild changes in clinical laboratory tests.
Future investigations are now necessary to highlight the influence of these cosmetic
procedures on various clinical laboratory parameters.

Abstract Body Hidradenitis Suppurativa is an autoinflammatory disorder ofkeratinization with a prominence of B cells and plasma cells, however B cell targeted
therapies are not currently in development for HS. We conducted an open-label proof
of concept clinical study using Fostamatinib (a spleen tyrosine kinase inhibitor) toassess the safety, tolerability and clinical response in moderate to severe HS. Twenty
participants were administered fostamatinib 100mg BID for 4 weeks, escalating
to 150mg BID thereafter until week 12. Participants were assessed for adverse
events and clinical response (Hidradenitis Suppurativa Clinical Response [HiSCR],
International Hidradenitis Suppurativa Severity Scoring System [IHS4], including
serology and skin biopsies. All twenty participants completed the week 4 and week 12
endpoints. Fostamatinib was well tolerated in this cohort with no grade 2/3 adverse
events reported. 85% achieved HiSCR at week 4 and 85% at week 12. The greatest
reduction in disease activity was seen at weeks 4/5 with worsening in a proportionof patients thereafter. Significant improvements were seen in pain, itch and quality oflife. Clinical Response was significantly associated with elevated baseline serum IgG
and C-Reactive Protein suggesting increased clinical efficacy in individuals with B-cell
dominant disease. This study also provides the first evidence to suggest that specific
B cells/plasma cells targeting may be a viable therapeutic strategy in HS.

21

Clinical Research - Interventional Research

LB1701Skin condition impacts SPF testing and what is unique for mineral sunscreen?
Y. Fu1, X. Li1, Y. Sun1, Y. Tan2
1
Johnson & Johnson Consumer Inc, Shanghai, China, 2Shanghai Skin Diseases
Hospital, Shanghai, China

Abstract Body
Background: The evolving toxicology assessments of US Food and Drug
Administration (FDA) for chemical sunscreens, combined with their potential tocause skin irritation, especially in sensitive skin, and the increasing awareness ofenvironmental impact, have driven demand for mineral sunscreen alternatives.
Current SPF testing only evaluates chemical sunscreen as a standard product,
highlighting the limited knowledge and eminent need for mineral sunscreen research.
Our study examines the potential impact of subject skin attributes on mineral andchemical SPF testing. Method: This study includes two post-hoc analysis from 49
SPF studies and a randomized controlled trial with 226 subjects. All studies were
performed in reference to ISO 2444. From the 49 SPF studies, pairwise correlation
was determined between the SPF of standard chemical sunscreen (P2) with subject
skin color (L*, a*, b*, ITA). In a separate study, correlation analysis was performed
with 226 subjects to investigate the associations between SPF of mineral sunscreen(S) and P2, with skin attributes including skin type, texture, hydration, and sebum.
Result: Meta-analysis of 49 SPF studies revealed a negative correlation between
SPF value of P2 to b*. The analysis of skin attributes and SPF testing among 226
subjects demonstrated a positive correlation between skin hydration (r = 0.261) andtexture (r = 0.235) with SPF of mineral product S. In contrast, the data showed anegative correlation between skin hydration (r = -0.398) and texture (r = -0.369) with
P2. Discussion: This study aims to understand the potential influence of subject
skin characteristics on SPF testing to provide new insights on the testing methods
for physical sunscreens. Collectively, our data demonstrated that SPF is highly
correlated with yellowish skin tone. Moreover, the contrasting trends between mineraland chemical sunscreens with skin attributes suggest the need to consider mineralsunscreen reference standards in ISO test methods.

|

Late-Breaking ABSTRACTS

LB1702

Lebrikizumab does not impact vaccine-induced immune responses: Results from aphase 3 study in adult patients with moderate-to-severe atopic dermatitis
J. Soung7, V. Laquer1, J. F. Merola2, S. Forman3, H. Elmaraghy4, E. Meskimen4, C. Hu4,
C. Natalie4, E. Pierce4, H. Torisu-Itakura4, E. Gil5, A. Jarell6
1
First OC Dermatology Research, Fountain Valley, California, United States, 2Harvard
University Boston, MA, Boston, Massachusetts, United States, 3Forward Clinical Trials,
Tampa, Florida, United States, 4Eli Lilly and Company, Indianapolis, Indiana, UnitedStates, 5Almirall SA, Barcelona, Catalunya, Spain, 6Allcutis Research, Portsmouth, New
Hampshire, United States, 7Southern California Dermatology, Santa Ana, California,
United States

Abstract Body Lebrikizumab (LEB) is a monoclonal antibody (Ab) that has shown
efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) in
Phase 2/3 trials. LEB targets IL-13 and inhibits signaling of the IL-4Rα/IL-13Rα1complex. The potential immunomodulator effect of LEB necessitates investigating its
impact on immune responses. ADopt-VA was a US Phase 3, 16-week (W) randomized,
double-blind, placebo-controlled study to assess LEB impact on vaccine immune
responses in adult patients with moderate-to-severe AD. The primary endpoint
was the immune response to 2 vaccines, the Tdap (Diphtheria/Tetanus Toxoids/
Pertussis) vaccine and MCV (Meningococcal (Groups A, C, Y, and W-135)) vaccine.
LEB was given as a 500 mg loading dose at baseline and W2, followed by 250 mg LEB
Q2W. At W12, both vaccines (Tdap and MCV) were administered to all patients, LEB
group N=107, Placebo (PBO) group N=81. Immune responses were determined by Ablevel differences between W12 and W16. Secondary efficacy endpoints at W16 were
Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI 75)
scores. For Tdap, 73.6% of LEB patients had a positive Ab response vs 73.4% for PBO,
90% CI, 0.3 (-10.2, 11.2). For MCV, LEB patients had an 86.9% positive Ab response
vs 75.0% for PBO, 90% CI, 12.2 (2.5, 22.0). IGA (0,1) was achieved by 40.6% of LEB
patients vs 18.9% receiving PBO (p=<0.001); EASI 75 was achieved by 58.0% and32.7% (p<0.001), respectively. The safety profile was consistent with previous LEB
trials. These data show that LEB does not negatively impact immune responses for
Tdap or MCV vaccines in adults with moderate-to-severe AD.

LB1703

LB1704

A. Blauvelt1, J. Gudjonsson2, R. Matheson1, R. Liu3, L. Shi3, H. Photowala3, B. Ehst1
Oregon Medical Research Center, Portland, Oregon, United States, 2Department of
Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, UnitedStates, 3AbbVie Inc, North Chicago, Illinois, United States

H. Han, J. Kim, Y. Park, H. Kang
Department of Dermatology, Ajou University School of Medicine and Graduate Schoolof Medicine, Suwon, Gyeonggi-do, Korea (the Republic of)High induction dosing of risankizumab in patients with moderate-to-severe plaquepsoriasis: Interim results from the phase 2 KNOCKOUT study

1

Abstract Body Objective: Evaluate safety and efficacy of high induction doses ofrisankizumab (RZB) in patients with moderate-to-severe plaque psoriasis at week 16.
Risankizumab, a humanized IgG1 monoclonal antibody that inhibits the interleukin (IL)23 p19 subunit, is approved to treat moderate-to-severe plaque psoriasis. KNOCKOUT(NCT05283135) is an ongoing phase 2, double-blinded, single-center study evaluating
whether higher-than-approved RZB induction doses are effective in achieving andsustaining clearance of psoriasis following drug cessation. Numbers of resident
memory T cells (Trm), which depend on IL-23 for survival, are also being assessed.
Patients with moderate-to-severe plaque psoriasis were randomized 1:1 to receive
RZB 300 mg or 600 mg subcutaneously at weeks 0, 4, and 16 and will be followed
long term with no additional RZB dosing. We report a blinded interim assessmentof safety and efficacy at week 16 (after 2 doses of RZB; cutoff date December 2,2022), including mean percent improvement from baseline in Psoriasis Area andSeverity Index (PASI) and proportions of patients who achieved ≥75%/≥90%/100%
PASI improvement (observed cases). KNOCKOUT enrolled 20 patients; 18 completed
dosing and were included in efficacy analyses. At week 16, mean (95% CI) percent
improvement from baseline in PASI in the combined 300 mg/600 mg groups was
97.5% (94.8%, 100%), and 100%/94.4%/66.7% of patients achieved PASI 75/90/100.
Incidence of adverse events was low and similar to previous RZB studies in psoriasis.
In conclusion, high RZB induction doses were well-tolerated; two-thirds of patientsachieved complete skin clearance after 2 doses at week 16. Ongoing long-term
assessments will evaluate clinical effects following the third RZB dose, maintenanceof efficacy after RZB cessation, and Trm numbers.

Stromal targeting therapy maintains the treatment effect of melasma: A 32-week,
prospective, randomized split-face study

Abstract Body Melasma relapse is almost common after discontinuation of
conventional treatment. Recent studies have suggested that photoaging dermis
is main pathomechanism of melasma emphasizing stromal targeting therapy. We
investigated maintenance effect of microneedling radiofrequency (RF) for melasma
treatment. Subjects with melasma were administered oral tranexamic acid and triple
combination cream for two months and a randomly assigned half face was treatedwith RF. After discontinuation of conventional therapy, the half face RF continued
monthly over 6 months. Modified melasma area severity index (mMASI) score andL* value by a chromameter were collected monthly. Fifteen patients were enrolled
and eleven completed the 8-month study. At 2nd month of conventional therapy, allsubjects showed improvement with a 64% reduction in mMASI score. With continuous
RF treatment, the improvement was well maintained; whereas in untreated side, theΔ L* gradually decreased, returning to the baseline after the conventional therapy
ended. The continuous RF therapy is beneficial in maintaining the conventional
therapy of melasma suggesting the protective effect of stromal targeting therapy inmelasma development.

22

Clinical Research - Interventional Research

LB1705WITHDRAWN|

Late-Breaking ABSTRACTS

LB1706Development of a novel dry iontophoresis glove for the treatment of primary palmar
hyperhidrosis
H. Pakhchanian1, A. Maignan1, S. Antonevich1, N. Daza1, N. Byrd1, R. Raiker2
1
The George Washington University, Washington DC, District of Columbia, UnitedStates, 2West Virginia University, Morgantown, West Virginia, United States

Abstract Body Primary palmar hyperhidrosis is a debilitating condition that induces
excessive sweating and is associated with a lower quality of life and psychosocial
distress. The current standard of care includes topical aluminum chloride (AC),oral anticholinergics (OA), and tap-water iontophoresis (TWI). However, research
has shown that AC is less effective on glabrous skin, OA can cause intolerable side
effects, and TWI is a immobilizing procedure with low compliancy. Therefore, the goal
was to create a localized treatment modality that could be equally effective while
also providing maneuverability for daily tasks and limiting systemic side effects.
To address this, a glove-shaped dry iontophoresis (DI) prototype was devised. A
3D model of the glove DI was made using computer-assisted design software. The
outer layer of the glove is composed of a machine-washable nylon/spandex blend
which provides durability, elasticity, and resistance to perspiration. The interior of
the glove has a removable five-layer construction, starting with an upper polyester
mesh layer. This layer acts as a supportive framework for the other layers, which
include a copper foil, a connective polyester mesh layer, a silicon insulating layer, anda lower polyester mesh layer. The silicon insulating layer helps promote perspirationand prevents leakage while the copper foil layer acts as an electrode and distributes
current throughout the palm. Lastly, the device's electrical housing consists of a
48x15mm microprocessor and a L298N motor driver that manages a unique parallel
circuit layout. A 1300mAh 9V lithium battery providing up to 25mA of current to thecopper electrodes within the glove was installed to meet established therapeuticlevels. The device’s efficacy is tested using a Galvanic skin response sensor thatmeasures skin conductance as a marker of sweat gland activity. Our prototype aims
to increase treatment compliancy by providing an convenient and effective solutionthat can provide relief for excess palmar sweating.

23

Clinical Research – Socio-behavioral and Health Services Research

LB1707

Cost implications of i31-GEP as a stratification tool for sentinel node positivity incutaneous melanoma
E. Ma1, M. A. Marchetti2, E. K. Bartlett2, Y. Hu1, J. H. Terhune1
Department of Surgery, University of Maryland School of Medicine, Baltimore,
Maryland, United States, 2Memorial Sloan Kettering Cancer Center, New York, New
York, United States
1|

Late-Breaking ABSTRACTS

LB1708Adoption and utility of asynchronous image capture skills learning module forfacilitation of an institution wide teledermatology program
C. Rundle1, J. Jacobs2, C. Diamond2, S. Chen1, M. Khetterpal1
Dermatology, Duke University Medical Center, Durham, North Carolina, United States,2
Duke University School of Medicine, Durham, North Carolina, United States

1

Abstract Body Commercially available gene expression profiling of primary cutaneous
melanomas (i31-GEP) has shown clinical utility in predicting sentinel lymph node
positivity in subsets of stage I melanomas. However, the cost implications of i31GEP in early-stage melanomas are not well characterized. The objective of thisstudy is to estimate the cost to detect one true positive sentinel lymph node via
gene expression profiling in early-stage cutaneous melanoma. We hypothesized thatroutine utilization of i31-GEP will be costly in T1 and T2 melanoma given the low
incidence of sentinel metastases in early stages. A Markov decision-analysis model
was created to simulate initial clinical outcomes and costs of patients choosing
between three selection strategies for sentinel lymph node biopsy (SLNB): i31GEP guided SLNB, SLNB all, or observe all. Biopsy complication rates and i31-GEP
accuracy were derived from published literature. Costs were extracted from national
Medicare reimbursement rates and Redbook. Compared to observing all patients, thenet cost to detect one true positive using the i31-GEP-guided strategy ranged from$700 K (high-risk T1a) to $55 K (T2b). The net cost to detect one true negative using
i31-GEP ranged from $12 K (T1b) to $166 K (T2b) compared to performing SLNB on
all patients. Our results suggest that universal use of i31-GEP is cost prohibitive inhigh-risk T1a. However, i31-GEP is more cost-effective in T1b and T2a melanomas asa tool to identify patients to avoid SLNB.

Abstract Body Background: We analyzed adoption and utility metrics for a learningmodel to improve image capture skills in primary care providers to facilitate a
Teledermatology (TD) program. Methods: Duke TD data from September 2021 – July
2022 was analyzed for adoption metrics including the ratio of providers enrolled
in the TD program who took the module and utility metrics including the rates ofsatisfactory versus unsatisfactory images for those who took the module comparedto those providers who did not. A pre- and post-module survey (2 and 3 questions,
respectively) queried confidence for image capture and module communication
efficacy, with a scale of 1-4 (4=very confident and very effective, respectively). We
used chi-square test to examine the association of module completion and image
quality, and odds ratio (OR) for participants vs non-participants of the course with
a 95% confidence interval (CI). Results: Of the 13 clinics offered the module, 92%(83/90) of providers completed the module. Of the 391 images submitted, 366/391(93.6%;12.3% unsatisfactory) were submitted by those who had completed thelearning module and 25/391 (6.4%; 36% unsatisfactory) images by those who
had not completed the module (Table 1). There was a significant improvement inquality in those who had taken the learning module (87.7%; OR: 4.28, 95% CI [1.7710.35], p=0.00089). Confidence ratings for photos were higher for post-survey (rash:
3.53, lesion: 3.52) vs pre-survey (rash: 2.88, lesion, 2.87). Average rating of module
efficacy was 3.8. Conclusion: Our module significantly improved image quality for TD
consultations and improved provider confidence.

LB1709

LB1710Prevalence of skin cancer screening visits in medicare data: A retrospective
cohort study
M. K. Nowakowska1, Y. Li2, C. Mohr2, B. Smith3, L. Ferris4, M. Wehner2
1
Baylor College of Medicine, Houston, Texas, United States, 2The University of Texas MD
Anderson Cancer Center, Houston, Texas, United States, 3Drexel University College ofMedicine, Philadelphia, Pennsylvania, United States, 4UPMC, Pittsburgh, Pennsylvania,
United States

Abstract Body Skin cancer screening is a common reason for dermatology visits,
though it is not guideline-supported in the US for the general population. There are no
estimates of how much of US dermatologists’ time is spent on skin cancer screening.
We aimed to investigate the proportion of dermatology visits that include skincancer screening over time. We used a de-identified, random sample of 4,999,999
Medicare beneficiaries aged ≥65 years from 2009-2018. We included all encounterswith dermatologists and excluded procedure-only visits. We identified skin cancer
screening encounters using a published skin cancer screening identification
algorithm, which was previously validated in Medicare patients and uses evaluationand management codes, as well as ICD-9/ICD-10 diagnosis codes. We calculated
the proportion of all dermatology encounters that included skin cancer screening.
9,679,601 dermatology encounters in 1,207,619 patients met inclusion criteria. Mostof the patients were female (55.5%), white (95.8%), and lived in the South (42.6%).
The mean age at first eligible encounter was 73.6 years (SD 7.8). 6,050,456 (62.5%,
95% CI 62.5%-62.5%) dermatology encounters included skin cancer screening. Skincancer screening encounters had a higher proportion of male patients, younger
mean patient age, and more frequently included history of skin cancer and actinic
keratosis (all P<0.0001). We observed an increase in the proportion of skin cancer
screening encounters over time, from 53.1% of dermatology encounters in 2009 to
73.0% in 2018. This study of 1.2 million Medicare beneficiaries with over 9.6 million
dermatology encounters shows that skin cancer screening comprises a significant
proportion of total dermatology encounters in the US, and this proportion isincreasing. Our findings highlight an important potential contributor to access issues
and long wait times in dermatology in the US.

Enhancing mobile teledermatology for community healthcare workers in rural Nepal
S. Ahuja1, N. Pradhan2, E. Shrestha2, K. Shekhar2
1
University of Washington School of Medicine, Seattle, Washington, United States,2
Dermatology, Dhulikhel Hospital, Dhulikhel, Bagmati, Nepal

Abstract Body Skin diseases are among Nepal's five most common health problems,
however, there are only around 125 dermatologists for a population of 26 million
people. Most dermatologists practice in urban areas, while 85% of the population
lives in rural areas. Thus, many patients must travel long distances in order to accessdermatologic care. To address this issue, a dermatology education program andstore-and-forward telemedicine program was created for community healthcare
workers in rural Nepal. A needs-assessment showed that CHCWs wanted additional
education on dermatologic diagnoses and treatments. CHCWs from 18 outreachcenters of Dhulikhel Hospital were invited to attend six virtual lectures on bacterial
and viral infections, fungal infections, acne, psoriasis, drug induced skin reactions,and STIs. Education-based presentations were delivered by dermatology faculty andresidents. CHCWs were added to a Viber group, where they could post cases beyond
their expertise and receive clinical guidance from dermatologists. Of the 32 CHCWs
invited to participate, 20 attended educational presentations and 17 completed theanonymous, pre-study and post-study surveys. CHCWs had a significant increase
in mean confidence in the diagnosis and management of dermatologic conditions
pre and poststudy (2.81 vs. 3.35 and 2.63 vs. 3.18, respectively). One month after
creating the Viber group, 37 patient consults were posted on the platform. The
average time to receive a response from an expert was 5 hours and 20 minutes. Of
the 36 patients who received a diagnosis and treatment, 97% avoided traveling to
Dhulikhel Hospital for dermatologic care. 88% of CHCWs agreed (47%) or strongly
agreed (41%) that they learned something about dermatologic treatment fromteleconsultation. All CHCWs agreed (82%) or strongly agreed (18%) that they would
send another patient for teleconsultation. Mobile teledermatology is a powerful tool
which can improve the capacity of CHCWs in rural Nepal. A similar approach can beused in other communities to reduce barriers to care.

24

Epidermal Structure and Barrier Function

LB1711

The transfection of double-stranded DNA induces cell senescence in cultured
human keratinocytes
A. Aioi1, T. Imamich2, J. Kashiwakura3
1
Septem Soken, Osaka, Japan, 2Laboratory of Human Retrovirology and
Immunoinformatics, Frederick National Laboratory for Cancer Research, Frederick,
Maryland, United States, 33) Department of Life Science, Faculty of Pharmaceutical
Sciences, Hokkaido University of Science, Sapporo, Hokkaido, Japan|

Late-Breaking ABSTRACTSLB1712

A clinical study of atomic-force microscopy-based rapid atopic dermatitis severity
assessment
J. Pereda1, H. Liao2, J. Wang3, E. Raun1, L. O. Nørgaard1, F. E. Dons1, E. Hwu1
Health Technology, Danmarks Tekniske Universitet, Lyngby, Hovedstaden, Denmark,2
Mechanical Engineering, National Taiwan University, Taipei, Taiwan, 3Departmentof Mechatronics and Robotics, Technische Universitat Munchen, Munchen, Bayern,
Germany

1

Abstract Body As the accumulation of senescent cells in tissues contributes tothe impairment of their homeostasis and increases the risk of many age-relateddiseases, cellular senescence has become a research focus. Since Hayflick reported
irreversible cell-cycle arrest in diploid cells, several senescent cell biomarkers,
including enlarged and flattened cell morphology, senescence-associated secretory
phenotype (SASP) such as IL-6 and IL-8, senescence-associated β-galactosidase(SA-β-Gal) activity and γ-H2AX, have been accepted. In addition, cytosolic doublestranded DNA (dsDNA) was recently identified as a novel senescence marker
in mouse embryonic fibroblasts. In skin, although studies on cell senescence in
cultured fibroblast are conducted flourishingly, there are few studies on keratinocyte
senescence in the culture. Therefore, we characterized keratinocyte senescenceinduced by transfection of dsDNA, comparing with the senescence depending on
replicative stress (cell passaging). The dsDNA-transfected normal human epidermal
keratinocytes (NHEKs) demonstrated enlarged and flattened shape, similar topassage 5 (P5) NHEKs. The mRNA expression levels of IL-6 and IL-8 in dsDNAtransfected NHEKs were significantly upregulated to 4.01±0.24 and 3.62±0.54 foldrespectively as well as the levels were significantly enhanced in NHEKs after P4. The
expression of senescent-associated SA-β-Gal activity was identified in the dsDNAtransfected P4 NHEKs, while SA-β-Gal activity was detected in P5 NHEKs. In addition,
ds-DNA transfection accelerated obvious γ-H2AX expression in P4 NHEKs, whereas
the expression was detected in P5 NHEKs. Conclusively, these results suggested
that dsDNA transfection into NHEKs induced cell earlier than cell passaging-induced
senescence, suggesting that dsDNA transfection into the cells provides an in vitro
model for studies on cellular senescence.

Abstract Body This study introduces high-speed dermal atomic force microscopy(HS-DAFM) as a diagnostic technique to assess the severity of atopic dermatitis (AD).
The study enrolled five AD patients and a control group of similarly aged individuals
with no history of skin barrier disease. Corneocytes were collected using the tape
stripping method and imaged using a HS-DAFM. A machine learning algorithm wasdeveloped to analyze the images and identify circular nano-objects (CNOs) on thecorneocyte surface. The CNO count per unit area was used to assess the severity of
AD. To validate HS-DAFM as medical diagnostic device, its output was compared withtraditional clinical severity assessments. The study found that the HS-DAFM images
from the control group displayed normal skin nanotexture (low CNO count), while
the images of the lesional area from AD patients displayed significant morphologicalchanges (high CNO count), with a large surface coverage and mean CNO counts
ranging from 270 to 550. A CNO count above 200 was associated with clinical AD
symptoms. The two subjects with the most severe AD exceeded a CNO count of 400.
Both the number and area of CNOs increased in skin closer to the lesional area. The
p-values of “control vs. AD non-lesional” and “control vs. AD lesional” were 0.0030
and 0.0098, respectively. HS-DAFM produced results in seconds, 50 times fasterthan traditional AFM, and orders of magnitude faster than biochemical assays. Thesefindings suggest that HS-DAFM is an effective tool for rapid AD severity assessment,
enabling preclinical treatment, quantitative evaluation of efficacy, and informing selfcare to prevent AD symptom progression. These capabilities allow dermatologists tomanage AD more effectively, potentially improving the quality of life for millions of
AD patients worldwide.

LB1713

LB1714L. Huygen1, 2, P. Thys1, A. Wollenberg2, 3, J. Gutermuth1, 2, I. Kortekaas Krohn1, 2
1
SKIN Research Group, Vrije Universiteit Brussel (VUB), Brussels, Belgium, 2Departmentof Dermatology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel(UZ Brussel), Brussels, Belgium, 3Department of Dermatology and Allergy, LudwigMaximilian-University, Munich, Germany

A. Celli1, M. Man2, J. Gonzalez1, T. Parenteau3, J. M. Meyer4, P. Elias1, 2,
K. Abuabara1, C. Grunfeld1, 2, T. C. Scharschmidt1, T. Mauro1, 2
1
Dermatology, University of California San Francisco, San Francisco, California, UnitedStates, 2Dermatology, San Francisco VA Health Care System, San Francisco, California,
United States, 3Geriatrics, University of California San Francisco, San Francisco,California, United States, 4Dermatology, Vanderbilt University Medical Center, Nashville,
Tennessee, United States

Skin barrier function assessment: Electrical impedance spectroscopy is lessinfluenced by daily routine activities than transepidermal water loss

Abstract Body Skin barrier function assessment is commonly done by measuringtransepidermal water loss (TEWL). An important limitation of this method is theinfluence of intrinsic and extrinsic factors. Electrical impedance spectroscopy (EIS)
is a lesser-established method for skin barrier function assessment. Some influential
factors have been described, but no guidelines exist regarding the standardizationof these measurements. Therefore, we evaluated the effect size of everyday daily
routine activities on EIS and TEWL measurements as well as their correlation withage and anatomical differences. Healthy participants (n=31) were stratified into three
age groups (18-29, 30-49, and ≥50 years) and EIS and TEWL measurements were
performed on the left and right volar forearm and abdomen. Body cream application
significantly decreased TEWL (15': p<0.0001; 90': p=0.0077) and EIS values (15':p<0.0001; 90': p=0.0015). Skin washing decreased TEWL after 15 minutes (p<0.0001)
and EIS values for 15 (p<0.0001) and at least 90 minutes (p<0.0001). TEWL wassignificantly increased 5 minutes after moderate to intense exercise (p=0.0007).
Coffee intake significantly increased TEWL on the abdomen after 60 minutes(p=0.0146). TEWL and EIS values did not correlate with participants’ age and no
anatomical differences were observed. Body cream application and skin washingshould be avoided at least 90 minutes prior to measurements of TEWL and EIS.
Exercise and coffee intake should also be avoided prior to TEWL measurements. EIS
may be a promising tool for skin barrier function assessment as it is less affected bydaily routine activities than TEWL.

Increased epidermal penetration in aged skin modulates systemic inflammation

Abstract Body Systemic inflammation, associated with impaired epidermal barrier
function, increases starting in middle age. However, transepidermal water loss
(TEWL), the traditional measure of “inside-out” barrier function, remains intact in
middle-aged and aged skin. We hypothesized that an additional source of age-related
inflammation is a defective barrier to outside agents (“outside-in”). We first comparedepidermal permeability to outside agents in untreated newborn vs. aged humanepidermis, using a previously validated fluorescent tracer, Ca2+ Green. Permeability,
as quantified by penetration volume, was 2-3x higher in aged skin. Since occlusion
does not increase inflammation in young skin but increases penetration of agentson the surface of the stratum corneum (SC), we hypothesized that using occlusion
to increase penetration through a defective barrier in aged skin would induce
inflammation in middle-aged (12 mos) but not young (8-12 weeks) mice. Occlusion
decreased SC hydration but did not change TEWL or the immune cell profiles in bothyoung and aged mice. Occlusion increased serum IL-1 beta and IL-6, both known
to be derived from epidermis, to a much greater extent in middle-aged mice andsignificantly enhanced Ca2+ Green permeability in middle-aged but not young mice.
Occlusion did not increase serum TNF-alpha, consistent with the minimal changes
seen in immune parameters. Finally, we demonstrated that larger but more widely
spaced, experimentally induced barrier defects that mimic those seen with decreased
hydration lead to increased outside-in penetration without increasing TEWL. Thesefindings suggest that an “outside-in” mechanism, linked to hydration defects, might
induce systemic inflammation derived from aging epidermis.

25

Epidermal Structure and Barrier Function

LB1715

Beyond established protection: Adaptive epidermal barrier functions regulate
systemic energy metabolism and body composition
X. Ding1, 2, S. Willenborg2, S. Satzinger2, S. Brodesser3, S. Eming2, 3, 4
School of Medicine, Shanghai University, Shanghai, China, 2Department of Dermatology,
Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany, 3Cluster of Excellence Cellularstress responses in Aging-associated diseases, Universitat zu Koln, Koln, NordrheinWestfalen, Germany, 4Center for Molecular Medicine Cologne, Universitat zu Koln, Koln,
Nordrhein-Westfalen, Germany
1|Late-Breaking ABSTRACTSLB1716

Dipotassium glycyrrhizinate inhibits hyaluronidase activity and preserves hyaluronic
acid level under UVB stress, contributing to skin moisture protection and aging
fighting benefits
Y. Qu, Y. Luo, M. Keh, R. Abe
Estee Lauder Companies R&D, Shanghai, China

Abstract Body The skin provides a life-sustaining structural and immunologicalbarrier for the organism. A defective epidermal barrier is a common featureof various human skin disorders, including ichthyosis, atopic dermatitis, andpsoriasis. Notably, these inflammatory skin diseases are prominent examples ofskin diseases associated with serious comorbidities such as short stature, obesity,
arthritis. However, the functional relationship between epidermal barrier defect andsystemic comorbidity is little understood. Recently, we generated a mouse modelwith epidermal-specific mTORC2 inactivation (RicEKO mouse) that resembles humanichthyosis in many aspects. In new studies, we now demonstrated that epidermal
barrier defects in RicEKO mice are associated with prominent systemic alterations.
To adapt to the cold environment, the RicEKO neonate remolds brown adipose tissuemorphogenesis. Further, in adulthood, mice exhibit increased energy expenditure,need higher glycolytic fuel utilization, and show increased lipolysis to compensate forthe energy loss. These altered metabolic processes in turn lead to growth retardation,lean phenotype, resistance to obesity, and altered lipidome profiles in fat depots.
Together, our findings highlight an important link between epidermal barrier function
and systemic metabolism at multiple levels which might contribute to comorbidity
pathology. We propose the RicEKO mouse as an interesting preclinical disease modelto untangle a functional communication between skin barrier defect and whole-bodymetabolism.

Abstract Body Hyaluronic acid (HA) is a key molecule involved in binding andretaining water in skin. Previous research has shown that HA downregulation during
photoaging may be due to changes in the expression and function of its degradation
enzymes, the hyaluronidases (HYALs). In our research, we utilized the 3D-cultured
human epidermal model and found that UVB irradiation could lead to HA degradation.
Dipotassium glycyrrhizinate (DG), is widely known for its anti-inflammatory properties
in skin care, however, its effect on skin hydration, particularly on HA, has not beenpreviously studied. Our results showed that 0.1% DG helps preserve HA level after
UVB exposure with a protection ratio up to 91.8%. Furthermore, we showed that DG
could inhibit hyaluronidase activity in a dose dependent manner. Rice ferment filtrate(Rice Power™ No.11α)1 is known to improve the skin's moisturizing ability and skinbarrier function to the level of naturally healthy skin due to increasing hyaluronic acidand other efficacies. Considering the possible synergy effect of DG and rice ferment
filtrate on HA, we designed topical treatments containing these two to evaluate thetreatments’ benefits in hydration both in vitro and in vivo. We showed the treatment
could increase HA levels by 40% in a 3D skin model. And in clinical, we observed
significant hydration improvement up to 72hrs after single treatment applicationcompared to untreated skin. In a 4-hour dry and cold environmental challenge
study, the skin hydration was kept at a significant higher level when compared tountreated skin and baseline. In a randomized controlled trial comparing cream andlotion regimes with lotion alone, both treatments improved skin hydration, elasticity,smoothness, texture, and reduced wrinkles and lines over 8 weeks. The regime
showed significant anti-aging improvement compared to the lotion alone treatment
as early as 1 week. These results demonstrate that these cosmetic treatments not
only relieve skin dryness, but also provide benefits towards anti-aging.

LB1717

LB1718

T. Nishiguchi1, 2, Y. Saito1, A. Hasegawa1, R. Abe1
1
Division of Dermatology, Niigata Daigaku Igakubu Igakuka Daigakuin Ishigaku Sogo
Kenkyuka, Niigata, Japan, 2Frontier Research Center, Pola Kasei Kogyo Kabushiki
Kaisha, Yokohama, Kanagawa, Japan

S. ShimSejong University, Gwangjin-gu, Seoul, Korea (the Republic of)

Apoptosis signal transduction in keratinocytes triggered by sequential receptor
activation of P2X7R and FPR1

Abstract Body Epidermal skin barrier is maintained precisely by positive and negative
controls of cell death. Lack of the cell death causes epidermal hyperproliferation,
whereas abrupt cell death induces loss of epidermis. Previously, we have revealed
that purinergic receptor P2X7 (P2X7R) and formyl peptide receptor 1 (FPR1) triggereda unique keratinocyte cell death in the lesional skins of patients suffering from severe
drug eruption. However, molecular mechanisms in the dying keratinocytes are still
unclear. Here, we investigated signal transduction in cultured keratinocytes upon
ligand stimulation of endogenously expressed P2X7R and FPR1. The expression
level of FPR1 was measured by qRT-PCR. The cell death was quantified by lactate
dehydrogenase release. As a result, P2X7R stimulation induced an increase in theexpression level of FPR1 in keratinocytes. FPR1 stimulation triggered transient
phosphorylation of ERK within 10 min, demonstrating the functionality of FPR1.
The FPR1-expressing cells also showed spontaneous cell death 6 h after ligand
stimulation. The cell death was inhibited by an apoptosis inhibitor but not by anecroptosis inhibitor, suggesting that stimulation for FPR1 induced apoptosis in
keratinocytes. We also revealed that the cell death was transduced by Gβγ-pERK
signal pathway instead of Gα signal pathway because the cell death response wasdiminished by corresponding signal specific inhibitors. Reactive oxygen species were
not increased after ligand stimulation, but its removal significantly inhibited the cell
death response, suggesting that cell death signal required constitutively produced
reactive oxygen species. Collectively, apoptotic signal transduction via P2X7R-FPR1Gβγ-pERK pathway was demonstrated in keratinocytes. Our results suggest potential
therapeutic targets of Gβγ signal pathway for the cell death related skin diseases.

Skin penetration and bioconversion of BIOGF1K enriched in compound K in vitro 3-D
human tissue model

Abstract Body The purposes of current study were to investigate the effect ofginsenosides from BIOGF1K enriched in compound K (CK) and compound Y (CY) on
the skin barrier function, the deposition in in vitro 3-D human tissue model (EpiDermFT™
Full Thickness 400), and to identify and quantify bioconversion of the ginsenosides
in artificial skin by utilizing the Fourier transform infrared spectroscopy (FT-IR) andliquid chromatography mass spectrometry (LC-MS), respectively. Epidermal barrier
integrity evaluated using transepithelial electrical resistance (TEER) was significantly
higher in the BIOGF1K treatment than the CY or CK individual treatment throughout
incubation (p<0.05). Skin deposition (%) of CY and CK from BIOGF1K treatment wasapproximately 4 and 2 times higher than the CY and CK single component treatment,
respectively. The absorption peak of O-H stretching was red-shifted from 3314 to3274 in BIOGF1K treatment and from 3321 to 3308 in CY treatment into skin tissue,
implying that a molecular unit having hydrogen bonds could be detached. The change
value in wave numbers of BIOGF1K (Δ 40) was greater than that of CY (Δ 13). At
the same time, CK was detected from total ion chromatography (TIC) after topicaltreatment of BIOGF1K and CY in artificial skin. Approximately 26.21% of CK was
produced after 2 hrs topical treatment of single CY, and there was no significant
difference in conversion rate from CY to CK between incubation time (p>0.05).
The results from the current study reveal that topical treatment of BIOGF1K more
effectively induced CK deposition as well as bioconversion of CY to CK than thatof a single treatment of CY or CK in in vitro 3-D human tissue model. Results fromthe current study suggest that BIOGF1K could be a useful cosmetic preparation forenhancing skin function due to deposition and bioconversion of CK.

26

Genetic Disease, Gene Regulation, and Gene Therapy|

Late-Breaking ABSTRACTSLB1719

LB1720J. Inen3, 4, P. S. McGrath1, 2, C. Han4, G. Bilousova4, I. Kogut4
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora,
Colorado, United States, 2Section of Developmental Biology, University of Colorado
Anschutz Medical Campus, Aurora, Colorado, United States, 3Bioengineering, Universityof Colorado Anschutz Medical Campus, Aurora, Colorado, United States, 4Dermatology,
University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

M. Liu1, J. Lee1, B. Riley-Gillis1, A. Abbasi1, J. Waring1, M. Reppell1, X. Zheng1,
S. Manson Brown2, T. Cheng2, R. Mehta2, S. Peterson2, N. Smaoui1
1
AbbVie Inc, North Chicago, Illinois, United States, 2Allergan Aesthetics, Irvine,
California, United States

Precise and efficient editing of the COL7A1 gene in RDEB derived iPSCs withCRISPR/Cas9 and prime editing

1

Genome-wide association study of rosacea finds enrichment in immune-related
genes

Abstract Body Recessive Dystrophic Epidermolysis Bullosa (RDEB) is an incurable
and heritable disease that subjects its patients to severe skin blistering, scarring, andmultiple internal organ damage, leading to high morbidity and mortality. It is caused bymutations in the COL7A1 gene which results in a dysfunctional type VII collagen (C7),a major component of anchoring fibrils in the epidermal basement membrane. While
many treatment options are being developed for RDEB patients, they carry significant
safety risks. The technology to generate induced pluripotent stem cells (iPSCs) andadvancements in gene editing technology have made them promising tools to curedebilitating diseases such as RDEB. Prime editing technology can be used to increase
both gene editing accuracy and efficiency. Utilizing this system to edit a prominent
mutation in the COL7A1 gene that causes RDEB, we hypothesize that we can generatea cell line with functional C7, providing a therapeutic solution to RDEB patients. With
our specialization, we will reprogram a patient’s fibroblasts into an iPSC line, expand
them indefinitely and genetically modify them with the prime editing system. The
on- and off-target effects have been assessed with whole genome CIRCLE-seq,
elucidating 39 potential off-target sites. Promisingly, preliminary analysis suggeststhat there is no off-target activity at the top sites sharing almost identical homology.
This strategy will allow us to potentially produce a quality iPSC line with functional
C7 that can be differentiated into any cells of interest, including functional skin thatcan be used for RDEB disease modeling. This method can potentially be expanded
for use as a platform for similar heritable genetic diseases and other downstream
applications.

Abstract Body Rosacea is a common inflammatory skin condition that affects as
many as 415 million worldwide and primarily manifests as reddening (flushing) on
different parts of the face. First classification of rosacea splits it into four distinct
subtypes depending on the location and symptoms of the affected areas; however,many individuals experience multiple subtypes together. While research has
implicated a range of biological systems and risk factors, the etiology of rosacea
remains poorly understood. In this study, we used the UK Biobank, a large wellphenotyped population database, to run a case-control genome-wide association
study (GWAS) of rosacea (Ncases = 9,405 and Ncontrol = 158,113) to better understandthe biological mechanism that may be affecting rosacea. To construct our cases, weused a combination of rosacea ICD10 codes and primary care codes (read codes)
to capture all phenotypic representation of rosacea. Our controls are individuals
without any skin-related medical codes in their health record and who have statedin the questionnaire that they appear their age or younger. In total, we have found 7
significant loci that reached genome-wide significance (p < 5e-8) after adjusting forsex and age, which include a previously implicated HLA gene. We report significant
associations with immune-related genes IRF1, TLR1 and IKZF1. A top significant
variant (rs5743618) is a missense variant that lies in TLR1, a gene that is expressedin the skin and has been associated with increased susceptibility to skin structure
infections. Furthermore, our GWAS results show a significant enrichment with otherimmune-related phenotypes such as asthma, ulcerative colitis, Crohn’s disease, anditch intensity from mosquito bites. While inflammation has been a known source forrosacea, our study highlights potential key immune-related genes that are involvedin the mechanism.

LB1721

LB1722

A novel pathogenic TPCN2 mutation detected for the first time in a Caucasianpatient confirms the dominant inheritance of albinism

Ablating ATP2C1 in human keratinocytes impairs intercellular adhesion, disrupts
epidermal integrity, and reveals therapeutic targets for Hailey-Hailey disease

N. Nagy1, 2, M. Pal1, 2, J. Kun3, G. Bence3, P. Urban3, M. Medvecz4, 5, B. Fábos6,
A. Neller1, J. Danis7, 8, Z. Hammad1, S. AlMarsomy1, E. Adam1, 2, A. Gyenesei3,
M. Szell1, 2
1
Department of Medical Genetics, Szegedi Tudomanyegyetem Szent-Gyorgyi Albert
Orvostudomanyi Kar, Szeged, Csongrád-Csanád, Hungary, 2ELKH-SZTE Functional
Clinical Genetics Research Group, Szegedi Tudomanyegyetem Szent-Gyorgyi Albert
Orvostudomanyi Kar, Szeged, Csongrád-Csanád, Hungary, 3Szentágothai ResearchCentre, Pecsi Tudomanyegyetem Klinikai Kozpont, Pecs, Baranya, Hungary, 4Departmentof Dermatology, Venereology and Dermatoncology, Semmelweis Egyetem, Budapest,
Hungary, 5ERN-Skin Reference Centre of Semmelweis University, Semmelweis
Egyetem, Budapest, Budapest, Hungary, 6Kaposi Mor Megyei Korhaz, Kaposvar,
Hungary, 7ELKH-SZTE Dermatological Research Group, Szegedi Tudomanyegyetem
Szent-Gyorgyi Albert Orvostudomanyi Kar, Szeged, Csongrád, Hungary, 8Department
of Immunology, Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Orvostudomanyi Kar,
Szeged, Csongrád, Hungary

J. L. Ayers1, A. Tiwaa1, M. K. Sarkar2, J. Gudjonsson2, C. L. Simpson1
1
Dermatology, University of Washington, Seattle, Washington, United States,2
Dermatology, University of Michigan, Ann Arbor, Michigan, United States

Abstract Body Albinism follows recessive mode of inheritance and 20 diseasecausing genes were implicated in its development. Using 20 gene panel, the genetic
background of 11 out of 17 Hungarian patients were elucidated. In patients withunidentified genetic background (n=6) whole exome sequencing was performed.
A novel pathogenic mutation (N687S) of the two pore channel two gene (TPCN2)
was identified in a 15-year-old patient confirming the dominant type of albinism. Our
discovery together with the recently described first Chinese case revolutionizes our
thinking about albinism, which has been so far known as a disorder with exclusively
recessive inheritance and emphasize that from now either recessive or dominant
inheritance should be considered in the everyday clinical practice.

Abstract Body Hailey-Hailey disease (HHD) is a rare autosomal dominantskin blistering disorder characterized by loss of adhesion between epidermal
keratinocytes, which leads to recurrent painful erosions, super-infections, andreduced quality of life. This disease is linked to mutations in ATP2C1 that deplete
SPCA1, a Golgi-embedded calcium ATPase important for processing and trafficking
adhesive proteins. Despite the discovery of its genetic etiology more than 20 years
ago, there are no FDA-approved treatments for HHD. Since ATP2C1 knockout mice
did not recapitulate the disease, we established human in vitro cellular and tissue
models of HHD to elucidate its pathogenesis and define new therapeutic strategies.
We leveraged CRISPR/Cas9 to ablate ATP2C1, generating TERT-immortalized humankeratinocytes lacking SPCA1. Utilizing a mechanical dissociation assay, we foundthat SPCA1-depleted cell monolayers exhibited defective intercellular adhesion.
Further analysis demonstrated that expression of critical adhesive proteins was
not altered in SPCA1-deficient cells; however, classical cadherins and desmosomal
proteins were not properly trafficked to intercellular borders, explaining the disruptionof cell-cell adhesion that drives skin blistering in HHD. Culturing SPCA1-deficient cells
in a 3D organotypic model of epidermis replicated key pathologic features of HHD,
including separation between keratinocytes and impaired localization of adhesiveand cytoskeletal proteins. To identify druggable pathways downstream of ATP2C1
loss-of-function, we performed RNA sequencing of SPCA1-deficient cells, which
revealed altered expression of major regulators of cadherin-mediated adhesion,
epidermal differentiation, oxidative stress, and growth factor signaling. In sum, weestablished a pre-clinical model of HHD that advanced our understanding of its
pathogenesis and uncovered novel therapeutic targets for this rare genetic blistering
disorder lacking proven treatments.

27

Genetic Disease, Gene Regulation, and Gene Therapy

LB1723Knocking down KLK5 by base editing restored desmoglein I expression in netherton
syndrome keratinocytes
V. Jayarajan1, G. Naso1, T. Brooks2, W. Qasim1, W. Di1
MCI, University College London, London, United Kingdom, 2GGM, University College
London, London, United Kingdom
1

Abstract Body Netherton Syndrome (NS) is a recessive genetic skin disease caused
by a loss of function mutation in SPINK5. Clinical features include ichthyosiform
erythroderma, trichorrhexis invaginata, atopic manifestations, and allergy. SPINK5
encodes for LEKTI, a Kazal-type serine protease inhibitor that inhibits kallikrein5(KLK5), a predominant serine protease involved in desquamation. Loss of LEKTI in
NS can cause over-degradation of corneocytes resulting in excessive desquamationof cornified layer in the skin and leading to a defective skin barrier. There is currently
no curative treatment for NS. We want to utilize the gene therapy approach for NS
and several gene correction strategies have been proposed. One of the strategies
is to knock down over-expressed KLK5 in NS to reduce KLK5 expression/activity,
consequently restoring skin barrier function. In this study, a third-generation cytosinebase editor (BE3) was used to knockdown KLK5 in keratinocytes carrying theheterozygous mutations (c.1732C>T and c.2274insT) in SPINK5 (NS-KCs). ThreesgRNAs (Q48X, Q90X, and SAX3) were designed to target KLK5 to create prematurestop codons or to disturb the splicing site. NS-KCs were genetically modified byelectroporating sgRNAs (single or combined) together with BE3 mRNA. The editing
efficiencies confirmed by whole exome sequencing were 35% to 55% (45%±10%).
The protein expression of KLK5 was significantly reduced in gene-edited NS-KCs andthe full-length desmoglein 1 protein (DSG1), a downstream target of KLK5 and oneof the cadherins of corneodesmosomes was increased. Furthermore, the activity of
KLK5 in NS-KCs was evaluated by AMC assay that used a KLK5 substrate conjugatedwith a fluorophore. A significant decrease in KLK5 activity was detected in the culture
media collected from the NS-KCs with knocked-down KLK5 compared to that from
NS-KCs without base editing. These results suggest that knocking down KLK5 could
decrease KLK5 proteolytic activity, increase DSG1 stabilization, and, thereby, restore
skin barrier function in NS.

LB1725

Clinical characteristics and quality of life in patients with acral peeling skin
syndrome: A pilot study
S. Yildiz, C. Prodinger, M. Laimer, J. Bauer
Dermatology and Allergology, University Hospital of the Private Medical University
Salzburg, Salzburg, Austria

Abstract Body Acral peeling skin syndrome (APSS) is a rare autosomal recessive
disorder characterized by spontaneous exfoliation of primarily palmoplantar
skin. Limited data on the clinical spectrum make it prone to underrecognition
and misdiagnosis, especially with the localized subtype of autosomal dominant
epidermolysis bullosa simplex. This study aimed to characterize the geno- andphenotypic scope of an APSS patient cohort to identify potential predictive anddiagnostic markers as well as approaches to optimize quality of life (QoL) and patientcentered care. Methods: A questionnaire survey study was conducted in 2022 at the
EB House Austria, Salzburg. Data on prevalence, phenotypical variability, course andtherapies were collected. The impact on QoL was assessed via the Skindex-29 and(Children’s) Dermatology Life Quality Index (DLQI). Results: Data from nine APSS
patients were analyzed. The most frequent symptom was blistering on hands andfeet (88.9%; n=8/9), followed by pain in the same areas (77.8%; 7/9). The mean VAS
pain score was 3.7 (range 1-9), with 44.4% (4/9) reporting a pain intensity above or
equal to 5. The DLQI/CDLQI yielded a mean score of 6.4 (range 1-14), with limitations
on sports activities being the biggest impact on QoL in 88.9% of patients (8/9),
followed by the disease’s symptoms (66.7%; 6/9) and limited choices of clothing
and footwear (55.5%; 5/9). Analysis of the Skindex-29 revealed high interpatientvariability, ranging from very mild/no impact of APSS on QoL to very severe. Water
aggravating the condition and hypersensitive skin had the biggest impact on healthrelated QoL. Conclusions: This study demonstrates for the first time that APSS
significantly impacts QoL. Therefore, early and accurate diagnosis and individualizedcare are crucial. This implies the need for a precise molecular testing strategy todifferentiate APSS from other skin disorders and awareness measures among all
relevant stakeholders.

|Late-Breaking ABSTRACTSLB1724

Autosomal recessive epidermolysis bullosa simplex caused by missense andinframe mutations in PLEC is associated with minimal or delayed muscular
dystrophy and possibly less laboratory abnormalities: A series of nine cases
W. Tu1, M. Yang1, Y. Hong1, Y. Lin1, P. Hou1, C. Wu2, K. Natsuga3, J. Lee1, J. A. McGrath4,
C. Hsu11
Dermatology, National Cheng Kung University College of Medicine, Tainan, Taiwan,
2
Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan,
3
Dermatology, Hokkaido Daigaku Daigakuin Igaku Kenkyuin, Sapporo, Hokkaido, Japan,
4
St John's Institute of Dermatology, London, United Kingdom

Abstract Body Our study aimed to explore the genotype-phenotype correlation of
epidermolysis bullosa simplex caused by PLEC mutations (EBS-PLEC). We analyzed
the genotype and phenotype of nine patients with EBS-PLEC through patient interview,
physical examination, mutational analysis, as well as skin biopsy with transmission
electron microscopy (TEM) and immunofluorescence microscopy (IFM). We also
used AlphaFold, a computer algorithm that predicts the 3D structure of proteins basedon their amino acid sequence, to study the structural changes of three missense
or inframe pathogenic variants found in this study. Nine EBS-PLEC patients were
included in this study. All nine patients had autosomal recessive disease, caused by
14 pathogenic variants, including 13 novel ones, in PLEC. Of these patients, five had
biallelic splice site, nonsense, and frameshift mutations and four had a missense or
inframe mutation on at least one allele. Patients with biallelic splice site, nonsense,and frameshift mutations were more likely to have overt muscular dystrophy thanthose with a missense or inframe mutation on at least one allele (100% vs 0%, p =0.0079). The diagnostic rate was 37.5% (3/8) for TEM alone and 71.4% (5/7) for IFM
alone, compared to the final diagnosis. Our study showed that missense or inframe
mutation in PLEC may lead to minimal or delayed onset of muscular dystrophy, which
carries important prognostic implication. Our results also indicate that EBS-PLEC
patients in Taiwan have distinct genetic mutations and that TEM may be more reliable
than IFM in diagnosing EBS-PLEC.

LB1726

Pathogenic contribution of ADAR1 mutations to severe plaque psoriasis
F. Assan1, M. McGrath1, M. Fremond2, A. Izmiryan1, Y. Crow2, B. Hervé1
1
Genetic Skin Diseases, INSERM U1163, Institut Imagine, Paris, France, 2Neurogenetics
and Neuroinflammation, INSERM U1163, Institut Imagine, Paris, France

Abstract Body Monogenic models of plaque psoriasis (PSO) remain rare to date.
Adenosine Deaminase Acting on RNA 1 (ADAR1) is a dsRNA editing enzyme which
loss-of-function (LOF) mutants account for interferonopathies. We report theassociation of ADAR1 variants with early onset severe plaque PSO. We identified bywhole exome sequencing (WES) in a Caucasian pedigree with autosomal dominant
early onset PSO and interferonopathy-like phenotype in the proband, a heterozygous(htz) missense mutation in the deaminase domain of ADAR1 (c.3355G>A), cosegregating with PSO. Transcriptomic Nanostring whole blood analyses of theinterferon (IFN) signature showed high IFN scores in all mutated siblings, and lesional
skin study showed a type I IFN signature without upregulation of type 17 immunity.
WES screening of 55 additional unrelated PSO cases identified 3 other ADAR1 htz
variants. Most ADAR1 mutated patients were refractory to conventional/ biologicaltherapies. In western-blot (WB) ADAR1 protein expression was dramatically reduced
in primary human keratinocytes (HEK) and/or peripheral blood mononuclear cells
from mutated patients. ADAR1 siRNA knock-down (KD) in ADAR1 wild type HEK
was associated (i) in qRT-PCR with a statistically significant (p≤0.05) upregulationof IFNB1, partially reversed by IFIH1 co-KD, and increased CXCL8, TNFA, IL17C
transcripts (ii) in WB with upregulated inflammatory activities (STAT1/3, p65-NFκB,
IRF3/7), differentiation blockade, and cell death markers induction (ZBP1, pMLKL,
caspase7, gasdermins), while supernatant proteome studies revealed an enrichment
of PSO-related pathways (IL20 family). Finally, lentiviral transductions of mutatedalleles in HEK were associated with an upregulation of IFN-related genes (IFNK, IFNB,IFI27). Altogether, this study establishes a new single gene model of PSO due to
ADAR1 LOF mutations, leading to skin/systemic IFN signature, opening new avenues
for precision medicine in PSO disease.

28Genetic Disease, Gene Regulation, and Gene Therapy

LB1727|Late-Breaking ABSTRACTSLB1728Establishing in vivo and in vitro models of hypermobile Ehlers-Danlos Syndrome fortherapy development

Searching for new candidate genes associated with atopic dermatitis in Ethiopian
families

P. Jesberg1, N. Diette1, K. Velmurugan1, J. Escamilla1, E. Elias2, M. Pavlova1, I. Kogut1,
G. Bilousova11
Dermatology, University of Colorado, Denver, Colorado, United States, 2Children's
Hospital Colorado, Aurora, Colorado, United States

S. Wang1, J. Elmgren1, J. Eisfeldt1, S. Asad1, K. Bilcha2, A. Befekadu2, C. Wahlgren1,
M. Nordenskjold1, F. Taylan1, I. Tapia-Paez1, M. Bradley1
1
Karolinska Institutet, Stockholm, Sweden, 2University of Gondar, Gondar, Ethiopia

Abstract Body Ehlers-Danlos Syndrome (EDS) is a group of genetic connective tissue
disorders characterized by hyperextensible skin, joint hypermobility and cutaneousfragility. EDS is primarily caused by mutations in genes encoding collagens orproteins involved in collagen biogenesis. The lack of reliable in vivo and in vitro
models precludes our ability to fully characterize the EDS phenotype, especiallyin the most common form of EDS, hypermobility-type (hEDS). Genetic causes of
hEDS are poorly understood. Therefore, recapitulating the hEDS phenotype in a
reliable 3D model opens doors to phenotype characterization, causative mutation
validation, quantitative diagnostic modalities, and therapeutic testing. We firstestablished a skin xenograft model of hEDS by healing wounds inflicted on the backsof immunodeficient mice using human keratinocytes and EDS patient fibroblasts.
The developed EDS skin xenografts showed disorganized collagen fibrils in theextracellular matrix, resembling those seen in skin biopsies of hEDS patients. To
complement our in vivo model, we also developed an in vitro cell-based model of
hEDS by generating 3D skin equivalents using hEDS human fibroblasts embeddedin thiolated-hyaluronan (HA-SH) fibrin gel scaffolds. Skin equivalents derived fromprimary and organoid-derived EDS fibroblasts have proven to be morphologicallysimilar to our xenograft model. We are currently conducting a broad-view proteomics
analysis through SomaScan, allowing us to analyze relative protein expression of
extracellular matrix components among our patients. Differences in expression offibrillar proteins known to play a role in collagen synthesis will be further assessedin our 3D models using immunohistochemistry (IHC) and electron microscopy (EM)quantification. Our in vivo and in vitro models may then allow development of novel
therapies for EDS.

LB1729Study of OSBPL2-induced skin keratinization disorders via PLCB3
Y. Wang1, 2, 3, A. Zhao1, 2, 3, P. Chaolan1, 2, 3, Q. Cao1, 2, 3, S. Zhang6, M. Li5, M. Li4
Dermatology Center, Shanghai Jiaotong University School of Medicine Xinhua
Hospital, Shanghai, China, 2Department of Dermatology, Shanghai Jiaotong University
School of Medicine Xinhua Hospital, Shanghai, China, 3Institute of Dermatology,
Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China,
4
Department of Dermatology, Children’s Hospital of Fudan University, Shanghai,
China, 5department of dermatology, The First Afliated Hospital of Soochow University,
Suzhou, China, 6Department of Biochemistry and Molecular Biology, Fudan University
School of Basic Medical Sciences, Shanghai, China
1

Abstract Body The study is the first to identify a novel pathogenic gene, OSBPL2,
in inherited keratosis dyskeratosis syndrome, and the first to show that it regulates
skin keratosis by influencing ubiquitination of the interacting protein PLCB3. In thisstudy, we diagnosed a case of skin keratosis, pigment abnormality accompanied byatopic disease, and deafness that had not been reported at home and abroad, andfound that the pathogenic gene of the disease was OSBPL2 gene by whole exome
sequencing and Sanger sequencing. We found that the expression of OSBPL2 protein
was significantly lower than in normal individuals. The proliferation level of patientepidermis was higher than in normal individuals (P<0.01, P<0.05), and the expressionof the terminal differentiation marker Involucrin was decreased (P<0.0001). In
addition, we also constructed an OSBPL2-knockout immortalized keratinocyte cellline (HaCaT) and similar phenotypes were detected. We determined PLCB3 as thetarget protein of OSBPL2 by enriching OSBPL2 and its interacting proteins. Compared
to controls, both patient eprdermis and OSBPL2 deficient cells showed a decrease in
PLCB3 expression. By inhibiting protein translation, we found that the degradation
rate of PLCB3 was accelerated in OSBPL2-deficient cells. Additionally, we found thatwhen OSBPL2 was highly expressed, the ubiquitination level of PLCB3 significantly
decreased. Finally, after supplementing PLCB3 in OSBPL2-deficient cell lines, theaffected proliferation and terminal differentiation levels of cells were partiallyrestored.

Abstract Body Introduction: Atopic Dermatitis (AD) is a complex inflammatory skindisease with a big genetic component in interplay with environmental factors. AD
is characterized by itch, eczematous lesions and increased risk of skin infections.
It often arises during childhood with a prevalence of 20-25% and may persist
into adulthood. The prevalence varies among populations, emphasizing the roleof genetics in AD aetiology. The major gene is FLG, several mutations have beenfound in the populations of Europe and Asia, but not in the African population
despite its high incidence. Materials and Methods: We collected saliva samples
from Ethiopian AD cases (n=171), controls (n=203) and families (n=5). All subjects
were collected in Gondar. All controls denied past or present history of AD or otheratopic manifestations. DNA was extracted and whole genome sequencing (WGS)
was applied to six individuals of one family. The impact of variants is evaluatedusing the prediction tools SIFT, Polyphen2, CADD and GERP++. Results: WGS of theEthiopian AD family revealed very rare variants in the FLG2 and NOD2 genes. The
variants are found in all affected individuals compared to a healthy family control.
In silico analysis predicted the variants to be damaging. Other variants in FLG2 havebeen pointed out previously to be associated with AD in African American individuals(1). NOD2 is a cytosolic receptor involved in bacterial recognition and transduces
signals leading to activation of innate immune pathways. Previous studies of Germancohorts suggested a role of NOD2 in AD (2). Discussion: Our study is aiming tountangle the genetics of AD in the Ethiopian population. Understanding which genes
are associated with AD in other ethnic groups is essential for a comprehensive viewof AD. 1.D. J. Margolis et al., J Allergy Clin Immunol (2014) 2.S. Weidinger et al., Clin
Exp Allergy (2005)

LB1730Concordance in the secretome of recessive dystrophic epidermolysis bullosa andcellular senescence reveals COL7A1 dependent perturbations
S. A. Koutsoukos1, M. Pavlova1, P. S. McGrath2, S. McGarvey1, J. Castillo Flores1,
A. Bruckner3, D. R. Roop1, I. Kogut1, G. Bilousova11
Department of Dermatology, University of Colorado Anschutz Medical Campus,
Aurora, Colorado, United States, 2Department of Pediatrics, University of Colorado
Anschutz Medical Campus, Aurora, Colorado, United States, 3Children's Hospital
Colorado, Aurora, Colorado, United States

Abstract Body Recessive dystrophic epidermolysis bullosa (RDEB) is a recessive
congenital skin disease caused by biallelic pathogenic variants in the gene, COL7A1,
which encodes type VII collagen (Col7). Deficiencies in Col7 cause a dysfunctionaldermal-epidermal junction resulting in a clinical presentation that includes severe
generalized blistering. Patients living with RDEB have a 90.1% risk of developing
aggressive squamous cell carcinoma (SCC) with high metastatic potential at aconsiderably younger age (by age 55) relative to the general population, whichsuggests a premature aging phenotype. In the following study, we investigated therole of Col7 in cellular senescence, and more specifically the senescence associatedsecretory phenotype (SASP), in primary patient derived fibroblasts (RDEB-F COL7A1-/-)
as well as organoid derived fibroblasts (ODF) generated from primary fibroblasts
transitioned through induced pluripotency that were either uncorrected (RDEB-ODF
COL7A1-/-) or genetically corrected using CRISPR Cas9 (RDEB-ODF COL7A1+/-).
Proteomic analysis of the secretome of RDEB-F COL7A1-/-, RDEB-ODF COL7A1-/-, andRDEB-ODF COL7A1+/- revealed numerous Col7 dependent perturbations, includingchanges in matrix metalloproteinase-2 (MMP2) secretion. Increased MMP2
secretion is associated with aggressive cancer metastasis and tissue aging. MMP2
secretion in RDEB-F COL7A1-/- and RDEB-ODF COL7A1-/- were both significantly higher
than that in corrected RDEB-ODF COL7A1+/-, suggesting a broader role of Col7 intissue remodeling and cancer metastasis. Additional proteomics studies, including
SomaScan, are currently underway to elucidate other Col7 dependent perturbations
associated with SASP and reveal novel targets causal in aggressive RDEB
associated SCC.

29

Genetic Disease, Gene Regulation, and Gene Therapy|

Late-Breaking ABSTRACTSLB1731

Human keratinocytes show changes in gene expression in response to cigarettesmoke exposure, of relevance to inflammatory skin disease
L. Johnston, M. Etorban, G. Grimes, M. Elias, S. Brown
Institute of Genetics and Cancer, The University of Edinburgh College of Medicine andVeterinary Medicine, Edinburgh, Scotland, United Kingdom

Abstract Body Cigarette smoking has well known effects on skin aging and as
a risk factor for psoriasis, but the association with atopic eczema is less clear.
Epidemiological studies suggest early-life exposure to passive smoke may
be protective for eczema, but FLG null genotype reverses this effect. Primary
keratinocytes represent a first line of defense against airborne chemicals, so wesought to investigate the direct effects of cigarette smoke on gene expression ina controlled environment in vitro. Primary human keratinocytes (KC) were isolated
from consented donors undergoing skin surgery. FLG wild type cells were cultured
as monolayers and cigarette smoke exposure modelled using standardized cigarettesmoke condensate (CSC) added at 10ug/ml for 4 hours. Gene expression wasquantified by RNA-seq; transcriptomic analysis used GSEA (UC San Diego and Broad
Institute). CSC treatment decreased expression of genes involved in ECM-receptor
interaction (GSEA enrichment -0.50, padj=0.033) but increased cornified envelope
genes (enrichment 0.72, padj<10-4) and increased IL-17 signaling (enrichment 0.67,
padj<10-4). SiRNA-FLG knockdown increased the expression of genes involved withinnate immunity, whilst the combined effect of CSC and FLG knockdown showeda marked increase in MMP9 expression (enrichment 1.22, p<10-4), a biomarker for
atopic inflammation. These findings are in keeping with known and novel biology:
a decrease in ECM-receptor interaction and collagen in the accelerated aging
process; IL-17 signaling in the pathogenesis of psoriasis. We speculate that the
CSC-stimulated increase in cornified envelope gene expression (via aryl hydrocarbon
receptor signaling) may contribute to protection against eczema in early-life exposure,whilst changes in gene expression profiles with FLG knock-down may explain theobservational epidemiological effects. Further work is needed to investigate thesemechanistic pathways for potential therapeutic targets to mitigate disease risk.

30

Innate Immunity, Microbiology, and Microbiome

LB1732

Particulate matter modulates inflammation cytokine production and lipid formationin cutibacterium acnes-stimulated SZ95 cellY. Choi, Y. Roh, S. Seo, K. Park, M. Lee
Chung Ang University Hospital, Seoul, Seoul, Korea (the Republic of)

Abstract Body The skin is one of the main organs exposed to airborne particulatematter (PM). Recent some studies have demonstrated that PM is associated with
inflammatory response and various skin diseases. Acne is a chronic inflammatory
disease of the pilosebaceous unit caused by increased sebum production. Little is
known concerning the potential effects of PMs on acne inflammation. Therefore,
we conducted experiments to analyze the effects of PMs on C.acnes treated SZ95
cells. To investigate the effect of PM on C. acnes-treated SZ95, we injected Heatkilled C.acnes in SZ95 cell to induce acne-like status. PM, which mainly comprised
polycyclic aromatic hydrocarbons was used as reference PMs. After SZ95 cells wastreated with PM. Cell viability was measured by CCK-8 assay. The gene expression
was investigated by real-time PCR and protein expression was assessed by Westernblot. Intracellular lipid droplet formation was investigated by Nile Red O staining.
Results showed that PM-induced pro-inflammatory cytokine and lipid synthesis factor
mRNA expression and protein secretion in C. acnes-treated SZ95. In addition, whenC. acnes stimulated SZ95 was treated with PM, lipid synthesis droplets wereincreased. In conclusion, the results of this study indicate that PM induces lipid
synthesis and inflammatory response in C. acnes-stimulated SZ95 in vitro. Further
experiments are needed to determine which signal transduction pathways are
mediated by the activation of these reactions in subsequent experiments.

|

Late-Breaking ABSTRACTSLB1733Skin microbiota disruption is associated with disease severity in alopecia areata
J. Gay-Mimbrera1, P. Gómez-Arias1, I. Rivera-Ruiz1, M. Juan-Cencerrado1, F. J. GómezGarcía1, S. Sánchez-González2, D. Gómez-Garre2, J. Ruano1
1
Inflammatory Immune-Mediated Skin Diseases Laboratory, Instituto Maimonides
de Investigacion Biomedica de Cordoba, Córdoba, Spain, 2Laboratorio de Biología
Vascular y Microbiota, Hospital Clínico San Carlos-IdISSC, Madrid, Spain

Abstract Body Background: The skin microbiome is a complex microbiologicalsystem with multiple interactions that can lead to both local and distant changes inhomeostasis. Objectives: To determine the relationship between skin microbiota andseverity in alopecia areata patients. Methods: We interrogated 16S rRNA gene on 20naïve patients with severe (n=8) or mild (n=12) AA and healthy controls (n=4) using
Swab samples collected from lesional scalp areas and analyzed on an Ion Torrent S5
sequencer. Disease status was classified as mild/moderate(< 50% involvement and<1yr duration) and severe(=>1yr, ≥50% SALT, AT or AU). Linear discriminant analysis(LDA) effect size (LEfSe) scores were used to identify the taxa that best discriminatedbetween groups. Results: Alpha diversity did not differ among samples. However,beta-diversity (Jaccard) was different in mild (p=0.002) and severe AA (p=0.005)
vs controls. Our results indicated that taxa of healthy scalp was dominated by fourbacterial phyla: Actinobacteriota 56.1%, Firmicutes 27.2%, Bacteroidota 8.5%, andProteobacteria 7%, representing a total of 18 different groups. There were apparent
shifts in dominance associated with AA severity from Actinobacteriota (56.1% control;
48.4% mild; 37.9% severe) to Proteobacteria (7% control; 6.1% mild; 17.4% severe)groups. Species which showed LDA>2 between control and AA were Brevibacillus,
Anaeroplasma, Jeotgalicoccus, Asteroleplasma, Helicobacter (all p<0.05).
Conclusions: Amount of scalp microbiota does not vary between healthy subjects
and patients with AA. However, there are changes in relative bacteria population witha positive correlation between proinflammatory (Proteobacteria)/anti-inflammatory(Actinobacteriota) bacteria ratio and disease severity. Whether these changes areeither the cause or consequence of AA needs to be explored further.

LB1734

LB1735

Z. Yan1, N. Dang1, H. Liu2, F. Zhang2
1
Department of Dermatology, Shandong Provincial Hospital, Jinan, Shandong, China,
2
Shandong First Medical University, Jinan, Shandong, China

X. Fan, D. R. Roop
Dermatology, University of Colorado Anschutz Medical Campus School of Medicine,
Aurora, Colorado, United States

Abstract Body Leprosy, caused by the intracellular microbe Mycobacterium leprae,provides a perfect model to study the mechanism of host immune response against
intracellular bacterial pathogen. As a key part of innate immunity and the major hostof leprosy pathogens, macrophage dysfunction is an important reason for M. leprae
accumulation in lepromatous leprosy, while the mechanism remains unclear. In thisstudy, we performed single cell RNA sequencing on leprosy biopsy specimens, andanalyzed the gene expression profiles in macrophages. We found GPNMB, a kindof type I glycoprotein, was overexpressed in lepromatous leprosy, compared to theself-limited tuberculoid leprosy. Deficiency of MB21D2 in THP-1 cells showed lessproinflammatory cytokine production upon M. leprae infection, such as IL-6, TNF-α
and IL-1β. Consistently, we found addition of GPNMB led to significantly deficiency
of antimicrobial activity in macrophages, which indicated that GPNMB plays a keyrole in promoting M. leprae to escape host immune response. Mechanistically, wedemonstrated that GPNMB inhibits cellular autophagic flux by blocking the maturationof autolysosome. Upon IL-4 stimulation, the lysosme-localized GPNMB directlyinteracts with the lysosomal SNARE protein VAMP8, blocking the assembly of STX17SNAP29-VAMP8 SNARE complex, which mediates the fusion of autophagosome withlysosome. Thus, our finding unveils new mechanisms by which M. leprae escapes
innate host defense in the progressive form of leprosy and provides insights fordeveloping new strategies to treat intracellular microbes.

Abstract Body Cancer immunoediting is a dynamic process whereby the immune
system can both constrain and promote tumor development, which proceeds
through three phases termed elimination, equilibrium, and escape. Although thecancer immunoediting process has set the foundation for understanding the immune
system’s dual roles on cancer cells and establishing the basis for revolutionary cancer
immunotherapies, very few studies have captured cancer immunoediting in its earlystages due to lack of proper mouse models. To address this deficiency, we developed
a novel mouse model for fluorescent tracing of somatic, epithelial cell transformation
to study the role of immunoediting in skin cancer development. For the first time, ourmodel provides the direct visualization of epithelial cancer development in vivo andallows the observation of all three phases of cancer immunoediting. In addition, ourmodel also allows tumor-infiltrating immune cells to be traced during this process.
This model allowed us to utilize large-scale sequencing technologies and spatialtranscriptomics to measure genome-wide gene expression changes in tumor cells
and immune cells in the transition from equilibrium to escape phases. Our preliminary
data shows that the transition from equilibrium lesions to escape tumors involves
the upregulation of TGFβ signaling in escape tumors. We also observe changes
in the immune cell composition in the equilibrium phase and escape phase. In
the equilibrium phase, CD4+ and CD8+ T cells, NK cells, macrophages, Tregs, andGamma delta T cells are observed. In the escape phase, CD8+ T cells, NK cells, Tregs,
and macrophages expanded, while CD4+ T cells, dendritic cells, and Gamma delta T
cells disappeared. Altogether, our work provides novel insights into the mechanisms
driving phase transition during cancer immunoediting and changes in the immune
cell composition during epithelial cancer progression.

GPNMB supresses the antimicrobial activity of macrophages through targeting
VAMP8

Utilizing large-scale sequencing to depict changes in immune cells during cancer
immunoediting in epidermal neoplasms

31

Innate Immunity, Microbiology, and Microbiome

LB1736

Changes and their significance of Th1, Th2, Th17 cells and SCCA levels in peripheral
blood of elderly patients with atopic dermatitis
H. WanDermatology, Sichuan Provincial People’s Hospital, University of Electronic Science andTechnology of China, Chengdu, China|

Late-Breaking ABSTRACTSLB1737

Antivirulence therapy-a new paradigm in treating staphylococcal skin infections
R. Y. Kao
Microbiology, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong,
Hong Kong

Abstract Body Objective: To investigate the changes and significance of Th1, Th2,
Th17 cells and squamous cell carcinoma antigen(SSCA) levels in peripheral blood ofelderly patients with atopic dermatitis(AD). Methods: Twenty-two elderly AD patients(elderly AD group) and 16 healthy subjects(healthy control group) were enrolled in the
Department of Dermatology, Sichuan Provincial People's Hospital from March 2022 toJuly 2022. Clinical data were collected from elderly AD patients, as well as laboratory
parameters including peripheral blood EOS counts, total IgE values, and SCCA levels.
Flow cytometry was used to detect the proportion of Th1, Th2 and Th17 cells inperipheral blood CD4+T cells in the two groups. Visual characteristics were compared
between groups using the Mann-Whitney U test or one-way analysis of variance, andcorrelation analysis was performed using Spearman correlation analysis. Results:
Elderly AD patients were predominantly male, with severe and widely distributed skinlesions, lichenoid eczema mainly on the extensor sides of the extremities and back,and some patients had one or more systemic diseases. The peripheral blood EOS
count in the elderly AD group was significantly higher than that in the healthy control
group (P<0.05). The proportion of Th17 cells in the peripheral blood of the elderly AD
group was significantly higher than that of the healthy control group (P<0.05), andalthough the proportion of Th1 and Th2 cells was slightly increased compared withthe healthy control group, the difference was not statistically significant. Peripheral
blood EOS counts were negatively correlated with the proportion of Th2 cells(r=-0.441, P<0.05) and positively correlated with serum SCCA levels (r=0.612, P<0.01)
in elderly AD patients. Serum SCCA levels were positively correlated with SCORAD
scores in elderly AD patients (r=0.607, P<0.01). Conclusion: Elderly AD patients haveunique clinical features, mainly Th17 type inflammation. Serum SCCA levels in elderly
AD patients may reflect disease severity.

Abstract Body The human skin microbiota is comprising of mostly beneficial
microbes with a few pathogens or opportunistic pathogens. Some pathogenic
bacteria may cause chronic skin inflammation and induce undesirable skinconditions, from abscesses, cellulitis, to possible tumorigenesis. Antibiotics havebeen used to treat bacterial infections by aiming at eradicating all bacteria, badand good altogether. But the emergence and dissemination of multidrug-resistantbacteria has become a global healthcare issue as a result. Using a well-studied
community acquire methicillin-resistant Staphylococcus aureus(CA-MRSA) strain
USA300, antibiotic-induced pathogenicity was assessed in vitro and in vivo. We
have illustrated that β-lactam antibiotics and tetracyclines induced the expressionof multiple surface-associated virulence factors as well as the secretion of toxins
in in vitro studies, and in in vivo studies mice infected with MRSA and treated with
ampicillin or tetracycline showed enhanced bacterial pathogenicity. Non-antibiotic
antivirulence therapy suppressing the productions of virulence factors of S. aureus
seems to be a viable alternative therapeutic option. Methods: We constructed using
USA300 as the parental strain a series of deletants of know virulence regulatorssuch as agrA, saeQRS, saeR, saeS, and sigB, to assess their pathogenicity in miceskin abscess model. The CFU on abscesses were counted and compared. We
further used a potent broad-spectrum antivirulence compound Antenovus-J01
in a mice skin model to illustrate the efficacy of applying antivirulence agents intreating CA-MRSA infected wounds. Results: Deletion of major virulence regulatorsof USA300 rendered this strain of CA-MRSA lost its capability to form abscesses inmice skin and antivirulence compound Antenovus-J01 effectively reduced virulence
expression in mice and helped wound healing. Conclusion: Our findings asserts that
antibiotic-based therapy of staphylococcal infections may present risks for induced
pathogenicity and antivirulence therapy is an effective alternative therapeutic option
for staphylococcal skin infections.

LB1738

LB1739J. Han1, A. Lisco2, I. Sereti2, J. Segre3, H. H. Kong1
1
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda,
Maryland, United States, 2National Institute of Allergy and Infectious Diseases,
Bethesda, Maryland, United States, 3National Human Genome Research Institute,
Bethesda, Maryland, United States

A. Basgaran, E. Lymberopoulos, S. Paschke, D. Delanoue, J. Arney, M. Hobbs,
M. Alomari, N. Sharma
BioCorteX Ltd., London, United Kingdom

CD4 T-cell lymphopenia in distinct immunological contexts differentially affects
human skin microbiome and HPV skin colonization

Abstract Body The roles of specific immune components in host-microbial
homeostasis remain ill-defined. Idiopathic CD4 Lymphocytopenia (ICL) patients andpeople with HIV (PWH) have low CD4+T-cells in distinct clinical and immunologicalcontexts which provides a unique opportunity to study CD4+T-cell lymphophenia
in skin host-microbial interactions. As ICL and PWH have different susceptibility toopportunistic infections such as HPV-related diseases and neoplastic, autoimmune,
and inflammatory skin disorders, we hypothesized that they may exhibit different
skin microbiome shifts. We analyzed microbiome diversity by performing shotgun
metagenomic sequencing of skin samples from PWH, ICL, and healthy controls(HCs). The skin microbiomes of antiretroviral (ART)-naïve PWH (n=5, median CD4
48 cells/ mL) and ICL (n=8, median CD4 65 cells/mL) patients showed higher HPV
reads per kilobase (RPK). ICL patients had higher median alpha-HPV RPK than HCs(420 and 9, respectively; p=0.003). Both median beta-HPV and gamma-HPV RPK in
ICL and PWH (beta-HPV: 5300 and 967, respectively; gamma-HPV: 17906 and 450,
respectively) were significantly higher than HCs (beta-HPV RPK 61 and gamma-HPV
RPK 13). Our analyses suggest CD4+T cell lymphopenia may differentially affectskin microbiomes and clinical sequelae dependent on underlying immunodeficiency.
Investigating human skin microbiomes in distinct contexts can provide insights
into susceptibility to microbial diseases – HPV-related diseases in particular – andthe interactions between the human skin microbiome and immune deficiency andrecovery.

The microbiome and metabolome profile in Japan, South Korea, and the USA is
directly linked to filaggrin gene expression and incidence of atopic dermatitis

Abstract Body Skin health and barrier function are influenced by skin and gut
microbiomes through superficial changes and influences on host gene expression.
Filaggrin (FLG) is a key protein in this and mutations in its gene are responsible
for several xerotic conditions. Prior metabolomics studies have demonstrated
a correlation with microbial-derived metabolites, but the causative link is poorly
understood. We hypothesize that microbial-derived metabolites influencequantitative FLG expression levels. We investigate whether inter-country differencesin the incidence of atopic dermatitis (AD) are related to differential microbial andmetabolite profiles of skin and gut. 25,768 skin microbiome samples and 183,432
gut microbiome samples from the USA, Japan, and South Korea were available in
the BioCorteX proprietary engines. BioCorteX CarbonMirrorTM platform (v202303-30) performed microbiome analyses, inferred the metabolome profile frommicrobiome composition, and identified influences on host FLG expression. Skin andgut microbiome and metabolome profiles significantly differed between countries.
3 microbial-derived metabolites influenced FLG expression: hydroquinone, 17betaestradiol, and calcitriol. Hydroquinone increased FLG expression and was the mostprevalent metabolite produced by over 4,800 bacterial taxa. These taxa were inhigher abundance in the skin (51%) and gut (63%) of patients from South Korea, acountry with comparably lower incidence and severity of AD. We demonstrate thatmicrobiome-mediated control of FLG expression contributes to heterogeneity in theincidence and severity of AD. This is in contrast with previous literature which has
focused on mutation rather than quantitative expression. While hydroquinone isclassically a bleaching agent, in-silico concentration and quantification testing are
required to understand its differential effects.

32

Innate Immunity, Microbiology, and Microbiome|

Late-Breaking ABSTRACTSLB1740

LB1741Y. Yew1, 2, D. Tay2, S. Lim3, S. J. Wearne3, T. Mina2, E. Riboli4, 2, E. Lee5, 2, J. Lee6, 2,
J. Ngeow7, 2, P. Elliott4, 2, S. T. Thng1, J. E. Common3, J. Chambers2, 4, M. Loh2, 1, 4
1National Skin Centre, Singapore, Singapore, 2Lee Kong Chian School of Medicine,Singapore, Singapore, 3A*STAR Skin Research Labs, Agency for Science Technology
and Research, Agency for Science Technology and Research, Singapore, SG, academic/
govt, Singapore, Singapore, 4Genome Institute of Singapore, Agency for Science
Technology and Research, Singapore, Singapore, 5Clinical Research Unit, National
Healthcare Group Polyclinics, National Healthcare Group Polyclinics, Singapore, SG,corporate/medprac, Singapore, Singapore, 6Research Division, Institute of Mental
Health, Singapore, Singapore, 7Division of Medical Oncology, National Cancer Centre,
Singapore, Singapore

J. Xia1, 2, Z. Li1, Q. Zhong1, Q. Wei1, L. Jiang1, C. Duan2, H. Jia2, Y. Tan3, L. Han2,
J. Wang1, 2, 4, X. Liu5
1
State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for
Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China,
2
Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences,
Fudan University, Shanghai, China, 3Department of Skin & Cosmetic Research, Shanghai
Skin Disease Hospital, Shanghai, China, 4Human Phenome Institute, Fudan University,
Shanghai, China, 5Shenzhen International Graduate School, Tsinghua University,
Shenzhen, Guangdong, China

Abstract Body Atopic dermatitis (AD) is widely accepted to be a multifactorial
disorder. Methylation and microbiota profiles, both of which can be mediated byenvironmental exposures, could serve as ideal potential candidates in the bettermentof our understanding. To examine the potential causal role of host methylation in
affecting skin microbiome, we focused on 24 genetic loci previously reported to be
associated with AD by the EAGLE consortium (P<5x10-8), which were significantly
associated with 156 CpG sites (P<5x10-14; N~7,000). By further investigating 268
Asian individuals with both methylation and microbiome (metagenomics) data, thisidentified 21 significant CpG-species associations (P<7x10-7; Bonferroni corrected),
across nine genes and 19 species. Our top methylation hit was cg23003117 (MICB),
which was significantly associated with 6 species. In particular,the top hit Lactobacillus
gasseri (P=1.7x10-12) has been shown to suppress Th17 pro-inflammatory response
and attenuates allergen-induced airway inflammation in mouse model. Another top
species was Saccharomyces cerevisiae, which has been linked to psoriasis and AD.
Indeed, dysregulation of MICBexpression has been shown to cause autoreactive
T-cell stimulation and promote inflammation and autoimmune diseases. Improved
understanding of the potential role of host epigenetics on skin microbiome may
contribute to future development of novel therapeutic in AD.

Abstract Body The skin microbiome is highly individualized. However, it is believed
to primarily be driven by the physical and chemical environment, which can bepartially reflected by skin phenotypes such as pH, hydration and sebum. Uncovering
phenome-microbiome association is critical in decoding the driving force formicrobial variability. Meanwhile, skin aging is a dynamic process with a spectrum ofphenotypical changes, making it an attractive model to study microbiome-phenotype
interactions. Here, 822 facial microbial samples and phenotypes were assessed ina Chinese cohort, the largest population size to date for skin shotgun metagenomic
profiling. Our data revealed that among 14 measured variables, porphyrin andchronological age explained the most significant microbial variability. The biodiversity
increased with aging, and age-associated species across kingdoms were specified.
Microbiome undergoes active function selection from energy demands/growth tostress adaptation along aging. We further characterized microbial changes with skinaging traits. Using the multiple linear regression model, we predicted prematureaging/delayed-aging-related microbial species, mainly localizing to Moraxella
osloensis and C. acnes. We validated the biological functions in vitro of some hostmicrobe interactions predicted by the association network. M. osloensis regulated
collagen metabolism, extracellular matrix assembly and promoted cell senescencein human keratinocyte and fibroblast cells. Our study is of significance for designinginterventions against aging-related skin conditions.

LB1742

LB1743

Role of host epigenetics with skin microbiome in atopic dermatitis

Profiling of the skin surface metabolome, an essential bridge linking skinmicrobiome and skin phenome
H. Chen1, Y. Chen2, S. Cao1, Y. Zhou3, 4, J. Wang1, J. Xia5
1
Human Phenome Institute, Fudan University, Shanghai, China, 2Wuhan Metware
Biotechnology Co., Ltd, Wuhan, China, 3Institute of Dermatology and Department of
Dermatology of the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui,
China, 4Key Laboratory of Dermatology, Anhui Medical University, Hefei, Anhui, China,
5Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences,
Fudan University, Shanghai, China

Abstract Body The skin is a complex ecosystem harboring millions of
microorganisms. Resource availability (nutrients) is considered a crucial selection
pressure shaping the system, which can be assessed by skin surface metabolome.
Skin surface metabolome is also essential for addressing the underlying mechanism
between microbe-host interaction. Here, we first review metabolites on the skin fromvarious metabolome studies. We next detected and quantified metabolites throughour samples from healthy human forearm skin using five analytical approaches:
quantitative lipidomics, widely targeted lipidomics, widely targeted metabolomics,
and targeted 500 metabolomics and oxidized lipidomics. Our results showed thatthe diverse substances present on the skin surface, derived from the host (stratum
corneum, skin appendages and plasma), environment (xenobiotics) and microbial
metabolism, mainly comprised of lipids, amino acids, sugars, peptides, vitamins,
hormones, pheromones, and other xenobiotics. Our samples showed free fatty acids(FFAs) and triglycerides (TGs) are the core lipids on the skin surface, accounting
for approximately 90% of individual total lipids, with FFAs being the most abundant
subclass (55%) and TGs are the most diverse subclass. In addition, the polar
compounds on the skin primarily comprise amino acids, organic acids and theirderivatives, nucleotides and their metabolites, and hormones and hormone-related
compounds. Overall, our study provides a comprehensive overview of the skin surface
metabolome that will facilitate future studies for skin microbiome-host interaction.

Skin microbiome-phenome interactome reveals a central role of bacteria in skin
aging

Human skin keratinocytes support Ebola virus replication
A. M. Fleck1, P. T. Richards2, R. Patel2, O. Shtanko4, A. J. Klingelhutz2, R. A. Davey3,
K. N. Messingham1, W. Maury2
1
Dermatology, University of Iowa, Iowa City, Iowa, United States, 2Microbiology &Immunology, University of Iowa, Iowa City, Iowa, United States, 3NEIDL, Boston
University, Boston, Massachusetts, United States, 4Host-Pathogen Interactions, Texas
Biomedical Research Institute, San Antonio, Texas, United States

Abstract Body Ebola virus (EBOV) outbreaks are sustained through person-to-persontransmission. Anecdotal evidence indicates that virus can be transmitted from EBOVinfected deceased individuals to others during funeral preparations. Consistent with
this, viral RNA is detected on the skin at late stages of infection and infectious virus
is present in EBOV-infected macaque skin for as long as four days post-mortem.
However, the cellular source(s) of infectious virions on the skin have not been widely
investigated. The goal of this study was to identify the timing and identity of skin cells
infected with EBOV. Human skin explants suspended at the air/liquid interface ontranswell inserts were infected with wild-type Ebola virus or a model virus expressing
the Ebola GP protein (rVSV/EBOV GP). Explants that were exposed to increasing
doses of EBOV in the basolateral media demonstrated dose-dependent levels andtiming of infection. Virus replication was evident in the dermis and epidermis as early
as day 2 post-infection and the explants supported robust infection as late as day 12.
Immunofluorescent staining demonstrated EBOV antigen expression in cytokeratin
5+ keratinocytes. Similar observations were made using our rVSV/EBOV GP model
virus; viral titer and viral RNA both increased in a dose and time-dependent fashion
along with increasing spread of viral infection in keratinocytes localized to the lower
epidermis. Infectious virus was detected on the surface of the explants, suggestingthat virus trafficked through the dermis and epidermis to the surface of the skin.
Primary human keratinocytes also supported EBOV infection in vitro and infectious
virus peaked at days 5-7 pi. This study shows that epidermal keratinocytes can bedirectly infected by EBOV and are a source of infectious virus indicating that thesecells likely play a role in person-to-person transmission through skin contact.

33

Pharmacology and Drug Development

LB1744|Late-Breaking ABSTRACTSLB1745Anti-atopic dermatitis activity of alkaloid-epioxyzoanthamine isolated from
Zoanthid

Brilaroxazine topical liposomal-gel formulation displays efficacy in the imiquimodinduced psoriatic BALB/c mouse model

C. Hung1, Y. Hsu2, Y. Cheng3
1
School of Medicine, Fu Jen Catholic University, Taipei, Taiwan, 2Fu Jen Catholic
University, Taipei, Taiwan, 3Department of Marine Biotechnology and Resources,
National Sun Yat-sen University, Kaohsiung, Taiwan

L. Bhat, S. R. Bhat, A. Ramakrishnan, M. Amirthalingam
Reviva Pharmaceuticals Holdings, Inc., Cupertino, California, United States

Abstract Body Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy,
and inflamed skin that occurs most frequently in children but also affects adults.
However, common clinical treatments provide limited relief and have some side
effects. Therefore, there is a need to develop new effective therapies to treat AD.
Epioxyzoanthamine is a small molecule alkaloid isolated from Formosan zoanthid.
Relevant studies have shown that zoanthamine alkaloids have many pharmacologicaland biological activities, including anti-lymphangiogenic functions. However, there
are no studies on epioxyzoanthamine in the skin. In this study, we proved that it has
the potential to be used in the treatment of atopic dermatitis. Through in vitro studies,
we found that epioxyzoanthamine inhibited the expression of cytokines in TNF-α/IFNγ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylationof MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used
2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation
in a mouse model. Our results show that epioxyzoanthamine significantly decreased
skin barrier damage, scratching responses, and epidermal hyperplasia induced by
DNCB. It significantly reduced transepidermal water loss (TEWL), erythema, ear
thickness, and spleen weight and increased surface skin hydration. These results
indicate that epioxyzoanthamine from Zoanthid has good potential as an alternative
medicine for treating atopic dermatitis or other skin-related inflammatory diseases.

Abstract Body Background: Dopamine(D) and serotonin(5-HT) signaling pathways
play an important role in psoriasis pathobiology, an inflammatory-fibrotic disease
with no real cure. They lead to increased inflammatory mediators (TNF-α, IFN-γ, IL1β, IL-6, IL-8), keratinocyte activation and deterioration, and worsening symptoms.
Brilaroxazine (RP5063), a modulator of D and 5-HT receptors with strong D24(partial agonist) and 5-HT2A/2B/7 (antagonist) and moderate 5-HT transporter
affinity- may affect underlying psoriasis pathology and offer a potential treatment
option. Methods: This preclinical study used an imiquimod-induced psoriatic mousemodel (BALB/c) to evaluate topical brilaroxazine’s activity in a liposomal-aqueousgel (Lipogel) formulation. Two of the three animal groups (n=6 per) underwent
induction by application of 5% imiquimod to their shaved backs on Days 1-11. One
group received topical Brilaroxazine Lipogel on Days 1-11. Assessments included 1)
Psoriasis Area and Severity Index (PASI) scores (Days 1-12), skin histology for Baker’sscore based on H&E stained tissue (Day 12), and serum cytokine collection (Day12). One-way ANOVA followed by post hoc Dunnett’s t-test evaluated significance(p<0.05). Results: Imiquimod-induced animal Baker’s scores were higher vs. theSham non-induced control’s results (p<0.001). Brilaroxazine Lipogel had significantly(p=0.003) lower Baker’s scores vs. the induced Psoriasis group. Brilaroxazine PASI
scores were lower (P=0.03) than those in the induced Psoriasis group on Days 3-12,
with the greatest effect in the last 3 days. The induced Psoriasis group showed higher
Ki67 and TGF-β levels vs. non-induced Sham controls (P=0.001). The Brilaroxazine
Lipogel group displayed lower levels of these cytokines than those in the induced
Psoriasis group, Ki67 (P=0.001) and TGF-β (P=0.008), and no difference in TNF- α
levels versus the Sham non-induced controls. Conclusion: Brilaroxazine Lipogel
displayed significant activity in imiquimod-induced psoriatic animals, offering a novel
therapeutic strategy.

LB1746

LB1747

P. Chiang2, C. Chen1, S. Chen3
1
Chang Gung Memorial Hospital Linkou, Taoyuan, Taiwan, 2New Taipei Municipal
TuCheng Hospital, New Taipei City, Taiwan, 3Taipei Veterans General Hospital, Taipei,
TaiwanM. Hamang, D. Xu, J. Lucchesi, C. Buckman, J. Mc Entire, M. Shaikh, A. Yu, C. Whitesell,
T. Campbell, K. Thirunavukkarasu, Y. L. Ma
Eli Lilly and Company, Indianapolis, Indiana, United States

Oral toxicity associated with checkpoint inhibitor immunotherapy

Abstract Body Purpose: Oral toxicity associated with immune checkpoint inhibitors(ICIs) therapy has been reported but there is no well-established data. We aim toevaluate the clinical features, histology, treatment and impact on cancer therapyof oral toxicity during ICIs therapy. Methods: We enrolled patients in two medical
centers in Taiwan during January 2017- December 2021. Results: We identified 35
patients (median age ± sd, 58 ± 2.8 years [range, 30 to 78years]) who developed
oral toxicity. 16(48.5%) presented with mucositis, 3(9.1%) had oral lichen planus(LP) or oral lichenoid lesions, 7(21.2%) presented with both mucositis and LP,
and 7(21.2%) presented with SJS/TEN. Most responded well to systemic and /or topical corticosteroid. However, more than one-third patients (13/35, 37.1%)
needed interruption of IO. One patient even died from skin toxicity and its associatedcomplications. 60% patients had an initial positive tumor response or stable disease.
Limitations: This was a retrospective study and a relatively small study population.
Conclusions: Mucositis and LP were relatively common oral toxicity. Severe oral
toxicity might lead to interruption of IO. Over half of patients with oral toxicity had asurvival benefit.

Characterization of bleomycin induced skin and lung fibrosis mouse model

Abstract Body Scleroderma is a multisystem autoimmune disease involving
inflammation, immunity, vasculopathy, and fibrosis of skin and internal organs.
Bleomycin induced fibrosis is the most widely used animal model to study anti-fibrotic
effects of potential treatments for scleroderma. However, there is no consistentpositive control response on bleomycin fibrosis model, especially for skin fibrotic
effect. We have characterized a bleomycin induced skin and lung fibrosis mousemodel to evaluate antifibrotic effects of molecules targeting different mechanisms.
Male, 8-10-week old C57BL/6J mice with a body weight 25-28g were used for the
study. Mice were given sc daily injections with 100ul of 0.6mg/ml Bleomycin(GoldBio) in a 2x2cm flank area for 28 days. Mice were given either vehicle 10ml/kg/
bid, Pirfenidone 100-200mg/kg/bid or ALK-5i 30mg/kg/bid orally for 28 days startingon either day 0 or 7 post bleomycin injection. When compared to naïve mice, vehicle
plus bleomycin-treated mice lost body weight, increased skin and lung weights, had
induction of multiple pro-inflammatory and pro-fibrotic genes, and increased lunghydroxyproline content, along with significant skin and lung fibrotic histopathology
changes. When compared to vehicle treated mice, both Pirfenidone and ALK-5i
reduced lung weight, lung collagen1a1 protein and hydroxyproline contents, andimproved lung Ashcroft and histopathology scores. In skin, Pirfenidone and ALK-5i
tended to lower skin weight and fibrosis dermal width, but neither reached statisticalsignificance when compared to vehicle controls. Expression of Pro-inflammatory andfibrosis genes were altered by Pirfenidone and ALK-5i treatment, with ALK-5i having
more consistent and better improvement on most end points being analyzed. Our data
confirm that daily bleomycin sc injection produces a robust dermal and pulmonary
fibrotic response, but the model needs to be further optimized to demonstrateconsistent benefit from both experimental and positive control treatments.

34

Pharmacology and Drug Development

LB1748Cannabidiol inhibits lipogenesis by regulating Akt/AMPK-SREBP-1 pathway insebocytes
Y. Kwon1, J. Yoon2, H. Lee1, D. Kim2, 3, J. Lee2, 3, D. Thiboutot4, D. Suh2, 3, B. Park1
1Skin & Natural Products Lab, Kolmar Korea, Seoul, Korea (the Republic of), 2Seborrheic
Dermatitis and Hidradenitis Suppurativa Research Laboratory, Seoul National University
Hospital, Jongno-gu, Seoul, Korea (the Republic of), 3Seoul National University Collegeof Medicine, Seoul, Korea (the Republic of), 4Penn State College of Medicine, Hershey,
Pennsylvania, United States

Abstract Body Cannabidiol (CBD) is known to relieve pain, stress and inflammation.
Acne is one of the most common skin diseases. The pathophysiology of acne
involves not only genetic and environmental factors, but also other factors including
hyperseborrhea, over keratinization of follicular keratinocytes and overgrowth of
C. acnes. Side effect of topical acne therapeutic include skin irritation, erythema anddry skin. Therefore, there are actively making an attempt for less side effects, andeffective treatment in acne therapy. The objective of this study, in order to confirm
the applicability of CBD as an acne OTC drug, a research on the mechanism ofacne was conducted using a standard CBD and high-purity CBD derived from thegrown hemp in Korea smart farms. In this study, the inhibitory effect of CBD on lipid
synthesis, cell proliferation in sebocytes was examined. And then, we performed thatthe effect of regulating the expression of key transcription factors related to sebum
synthesis. Oil red O staining showed that inhibited by CBD treatment at all doses.
TUNEL staining results found that CBD treatment at promoted sebaceous gland cell
apoptosis. These data suggest that CBD inhibited cell proliferation, and decreased
sebaceous gland size. CBD increases p-AMPK and decrease p-Akt, suggesting that
CBD inhibits adipogenesis by regulating the Akt/AMPK-SREBP-1 signaling pathway.
We confirmed that CBD inhibits inflammation caused by hyperkeratosis in HaCaT.
The levels of CXCL8 and IL-1α cytokines in cells were decreased after CBD treatment.
Furthermore, the synergistic effect of the combination of salicylic acid (SA) and
CBD was studied. The lipid synthesis was inhibited by combination of SA and CBDtreatments in SEB-1. These results suggest that CBD can be used as a substance toalleviate acne by reducing excessive sebum formation.

LB1750|Late-Breaking ABSTRACTSLB1749Targeting NLRP3 inflammasome activation to inhibit skin inflammation andmodulate Th17 cell differentiation for the treatment of psoriasis
C. Yen3, 2, S. Yu1, 2
1
Department of Medical Research, Taichung Veterans General Hospital, Taichung,Taiwan, 2Integrated Care Center of Psoriatic Disease, Taichung Veterans General
Hospital, Taichung, Taiwan, 3Department of Dermatology, Taichung Veterans General
Hospital, Taichung, Taiwan

Abstract Body Psoriasis is a chronic skin autoimmune disease that has a significant
impact on the quality of life and may have severe comorbidities. Immune cells
would be attracted to the skin lesion and overexpress pro-inflammatory cytokines
to induce skin inflammation. Among these immune cells, the Th17 cell played an
important role in the pathogenesis of psoriasis. NLRP3 inflammasome activation
has been reported to be correlated with inflammatory diseases and pathologic T celldifferentiation. 3H-1,2-dithiole-3-thione (D3T), isolated from cruciferous vegetables,
has been reported to have anti-inflammatory effects and inhibit Th17 differentiation.
However, the possible mechanism of D3T in inhibiting NLRP3 inflammasome
activation remained unclear. The aim of this study is to investigate the effects of
D3T on decreasing skin inflammation and modulating Th17 cell differentiation
by inhibiting the activation of the NLRP3 inflammasome. The results showed that
D3T treatment could significantly decrease ear thickness, skin redness and scaling
compared to vehicle control group in the imiquimod induced psoriatic dermatitis
mouse model. D3T could reduce the expression of NLRP3 inflammasome in the skinsample and TNF-α stimulated HaCaT cells. Caspase-1 and IL-1β expression also
decreased after co-treated with D3T. IL-17A expressed CD4+ T cells was decreased in
the D3T treatment group. The mechanical study showed that D3T could inhibit NLRP3
inflammasome activation by inhibiting the JNK pathway in HaCaT cells. These results
indicated that targeting NLRP3 inflammasome activation is a promising strategy inthe treatment of psoriasis.

LB1751

PC111, an anti-FasL neutralizing antibody, blocks pemphigus blister formation in
in-vitro, ex-vivo and in-vivo human models

Downstream effects of IL-13Rα1 blockade on type 2 inflammation and Th1 immune
axis activation in atopic dermatitis

R. Lotti2, 1, A. Marconi2, 1, A. Amato1, B. Bennett1, J. E. Hundt3, C. M. Hammers3,
R. J. Ludwig3, C. Pincelli2, 1
1
PinCell s.r.l., Milan, Italy, 2Universita degli Studi di Modena e Reggio Emilia, Modena,
Emilia-Romagna, Italy, 3University of Lubeck, Lubeck, Germany

S. V. Reddy1, Z. A. Bordeaux1, A. Rajeh2, D. M. Sivaloganathan2, H. Cornman2,
A. Kambala2, J. Adams1, F. Cevikbas3, S. Kwatra2, M. Kwatra1
1
Anesthesiology, Duke University School of Medicine, Durham, North Carolina, UnitedStates, 2Dermatology, Johns Hopkins University School of Medicine, Baltimore,
Maryland, United States, 3ASLAN Pharmaceuticals Pte Ltd, San Mateo, California,
United States

Abstract Body Pemphigus is a rare and chronic autoimmune blistering disease due
to keratinocyte acantholysis. Treatments focus on immune suppression but areoften associated with a delayed onset of action, severe side effects and frequentclinical relapses. Therefore, innovative and non-immunosuppressive therapies areneeded to provide rapid, safe and long-lasting responses. Patients’ autoantibodies(PVIgG) are fundamental for initiating the pathologic mechanisms of pemphigus.
We have previously demonstrated that soluble Fas Ligand (sFasL) is essential for
blister formation, as it is rapidly up regulated and released from keratinocytes upon
PVIgG binding. In particular, FasL activates caspases, which degrade desmogleins,thus inducing acantholysis. Against this background, we have developed PC111, a
monoclonal antibody with high affinity to human FasL and potent inhibitory activity ofacantholysis, as shown by the keratinocyte dispase dissociation assay. We present
evidence that PC111 inhibits acantholysis in two different ex-vivo pemphigus models:
first, subcutaneous injections of PC111 reduce blister formation up to 50% in a dosedependent manner in an anti-desmoglein 1 and 3 scFv-induced model; secondly, wedemonstrate that PC111 blocks blister formation also in a PVIgG-induced model. In
addition, we have recently developed a new murine model, by swapping the FasL
murine gene with the human one and have used the new FasL humanized mousein the neonatal passive transfer pemphigus model: PC111 displayed a very highefficacy in blister inhibition in this setting. These results strongly support PC111 as apromising clinical candidate for the treatment of pemphigus.

Abstract Body Atopic dermatitis (AD) is an inflammatory skin disease characterized
by dysregulated type 2 inflammation. Interleukins (IL)-4 and IL-13 are key cytokines
mediating type 2 inflammation in AD, with IL-4 signaling through the type I receptor(composed of IL-4Rα and the common gamma chain) and IL-4 and IL-13 signaling
through the type II receptor (composed of IL-4Rα and IL-13Rα1). The most effective
way to inhibit type 2 inflammation remains unknown. In this study, we treated peripheral
blood mononuclear cells (PBMCs) isolated from 10 AD patients with either an antiIL-4Rα antibody to block both type I and II receptors or eblasakimab, a monoclonal
antibody that binds IL-13Rα1, to block only the type II receptor. We investigated thedownstream effects of blocking these receptors on cytokines involved in type 2
inflammation and other immune axes utilizing the Meso Scale Discovery panel in the
PBMC supernatants. We find that treatment with IL-13Rα1 blockade as compared
to IL-4Rα blockade resulted in statistically significant decreases in the release of
key cytokines implicated in Th2 inflammation, including TARC (p=0.0001), IL-13(p<0.0001), IL-4 (p<0.0001), IL-9 (p=0.0047), and MCP-4 (p<0.0001). Furthermore, ourdata demonstrate that IL-13Rα1 blockade did not induce an upregulation of the Th1
immune response as observed with anti-IL-4Rα therapy. Specifically, treatment witheblasakimab as compared to anti-IL-4Ra therapy did not lead to an increase in proinflammatory Th1 cytokines, including TNF-α (p=0.0319), IL-2 (p<0.0001), GM-CSF(p=0.0011), IL-12p70 (p<0.0001), and IP-10 (p=0.0017). Taken together, our findings
suggest that selective targeting of the IL-13Rα1 receptor in AD may lead to a morepotent reduction in type 2 inflammation while not activating the Th1 pathway.

35

Pharmacology and Drug Development

LB1752

OR-101: A next generation JAK3 selective compound
M. Howell, W. Ahmad, P. S. Walker, F. Hasan
Ornovi, Irvine, California, United States|

Late-Breaking ABSTRACTSLB1753

OR101, next generation selective JAK3, shows significant effectiveness in wellestablished murine models of inflammatory skin disorders
A. Gilhar2, W. Ahmad1, P. S. Walker1, M. Howell1, F. Hasan1
Ornovi, Irvine, California, United States, 2Technion Israel Institute of Technology, Haifa,
Haifa, Israel

1

Abstract Body The Janus Kinase (JAK) family of cytoplasmic non-receptor tyrosine
kinases includes JAK1, JAK2, JAK3 and tyrosine kinase 2. Upon activation, JAKs
activate the signal transducer and activator of transcription pathway to regulate
downstream signaling of inflammatory cytokines and growth factors. Targeting JAK
kinases with small-molecule inhibitors is effective in treating different disease types,
and identifying more selective pharmacologic JAK inhibitors is an ongoing R&D goal.
Preclinical tests characterized next generation JAK inhibitor, OR101, with selective
inhibition of JAK3-mediated inflammation. JAK3 is involved in signal transduction by
receptors that employ common gamma chain of type I cytokine receptor family (IL2R, IL-4R, IL-7R, IL-9R, IL-15R, IL-21R), so it is applicable to inflammatory conditions.
OR101 selectivity profile was delineated using an enzymatic assay (NanoBRET),
phenotypic kinome screens, and cytokine release assays. Ritlecitinib, a JAK3/TEC
inhibitor in Phase 3 inflammatory disease trials, was the comparator in all assays.
Enzymatically, OR101 exhibited an improved selectivity profile versus ritlecitinb, witha better JAK3 IC50 measurement. Kinase activity differences were confirmed using
the KINOMEscan assay: both OR101 and ritlecitinib exhibited potent JAK3 activity.
OR101 was 2 to 165-fold more selective than ritlecitinib with additional kinases(BLK, BTK, EGFR, ITK, JAK1, JAK2, TYK2), suggesting an improved selectivity profile.
Cytokine release assays stimulated peripheral blood mononuclear cells from healthy
humans with anti-CD3 to activate T cells in the presence/absence of OR-101 or
ritlecitinib for 24 hours. While inhibitory activity was similar against IL-2, IL-6, andIFN-g for both products, OR101 exhibited greater inhibitory activity against IL-4 andIL-15. These studies confirm the JAK3 selective profile of OR101 and suggest its
potential in inflammatory diseases characterized by JAK3 driven inflammation.

Abstract Body Psoriasis is a chronic, autoimmune, inflammatory skin disorderaffecting 2-3% globally. Skin of psoriasis patients is characterized by excessive
keratinocyte proliferation and aberrant keratinocyte differentiation in the stratum
corneum. Multiple inflammatory cell populations are observed within the lesions
including autoreactive T lymphocytes (Th17, Th1, Th22) that release IL-17, IFN-g, IL22, and TNF-a to potentiate disease pathogenesis. Other cytokines IL-6 and IL-21 alsoenhance IL-17 production from Th17 cells in a JAK-STAT–dependent manner. OR101
is a next generation JAK3-selective compound that blocks downstream signaling
mediated by receptors employing common gamma chain of type I cytokine receptor
family (IL-2R, IL-4R, IL-7R, IL-9R, IL-15R, IL-21R), so it has potential in inflammatory
conditions including psoriasis. OR101 efficacy was evaluated in a humanized murine
model of psoriasis: 50 immunodeficient mice (10 each group) were xenotransplantedwith human psoriatic skin and treated for 2 weeks with daily oral OR101 (30, 60, or
100 mg/kg), or vehicle, or with topical 2 mg dexamethasone twice daily as positive
control. Dose-dependent improvements were seen in epidermal thickness measured
by ocular micrometer (p<0.001 versus vehicle) and epidermal proliferation (p<0.01
versus vehicle). Blinded histology mean Baker scores were significantly better (p<0.05)
for the highest OR-101 dose versus the 2 lower doses and placebo and were similar
to positive control. Recovery of psoriatic features (eg, hyperkeratosis, parakeratosis,
acanthosis) based on histology was also dose-dependent. Similar improvements
were seen for infiltrating CD4 and CD8 T cells, antimicrobial peptides (hBD4, S100A7),
and inflammatory cytokines (TNFa, IL-17, IL-22). These animal studies demonstrate
OR101’s potential in psoriasis and other TH17-driven inflammatory skin diseases.

LB1754Treatment of human palmoplantar keratoderma skin equivalents with a TRPV3
antagonist, KM-001
M. Caley1, M. Idrissi1, L. Braiman2, E. Brener2, E. O'Toole1
Centre for Cell Biology and Cutaneous Research, Queen Mary University of London,
London, United Kingdom, 2Kamari Pharma, Ness Ziona, Israel
1

Abstract Body Pachyonychia congenita (PC) is an autosomal dominant (AD)palmoplantar keratoderma (PPK) caused by mutations in keratin genes, K6A, K6B,
K6C, K16 and K17. Haploinsufficient mutations in AAGAB, encoding p34, cause
punctate keratoderma type I (PPK1). Keratin 16 is a direct target for the epidermal
growth factor receptor (EGFR) and ERK1/2-mediated signaling. Knockdown of p34
in HaCaT results in increased stabilization of the EGFR. TRPV3 (Transient receptor
potential cation channel, subfamily V, member 3) is a cation channel with relatively
high permeability to calcium. The EGFR forms a signaling complex with TRPV3.
Activation of the EGFR results in increased TRPV3 channel activity and has a major
effect on epidermal homeostasis. We hypothesized that inhibition of TRPV3 mightreverse some of the pathological changes seen in PC and PPK1. Here, we describe
the effect of the TRPV3 antagonist, KM-001, on PC and PPK1 skin equivalent models.
The PC model was generated using HPV-immortalized keratinocytes derived from apatient with PC-KRT6A and compared to a normal control keratinocyte cell line. The
PPK1 model was generated by using shRNA targeting AAGAB with a non-targeting
control. An inactive Enantiomer was used as a control for KM-001. In the PC modela decrease in the number of cells with Ki-67 nuclear expression was seen with > 0.1µM suggesting that KM-001 decreased proliferation in the PC model. Nuclear loricrin
was observed in the PC model and was markedly decreased by KM-001. Nile Red
staining of lipids was reduced in the PC model and partially restored by KM-001 (0.1µM). In the hyperproliferative PPK1 model, proliferation was reduced by KM-001 (0.5µM). Involucrin and tranglutaminase 1 expression were reduced in the PPK1 modeland restored by KM-001 (0.05 - 0.5 µM). These results suggest a beneficial effect of
TRPV3 inhibition in both PC and PPK1 which is being explored further in a phase 1B
clinical trial (NCT05435638).

36

Photobiology

LB1755

LB1756

M. Meloni1, F. Rescigno1, E. Caviola1, A. D'Amato2
VitroScreen Srl, Milan, Italy, 2Department of Pharmaceutical Sciences, University of
Milan, Milan, Italy

1

An advanced microphysiological system for dermatological applications

1

Abstract Body In the field of 3D tissue systems for in vitro dermatological research,a major limitation consists in the presence of exogenous scaffold that doesn’t allow
to recapitulate either the physiological assembly of human dermal stroma(de-novo
ECM assembly and architecture) or the dynamic remodeling process in aging, fibrosis
or photoaging. We developed a miniaturized dermis, as 3D scaffold free spheroid,
to create an advanced Microphysiological System(MPS) presenting a natural 3D
architecture with strong cells-ECM interaction. Here we applied the model to address
the UVA-induced photoaging process. Human dermal fibroblasts(50 year old donor)
were seeded in InSpheroTM plates to generate scaffold-free spheroids (diameter 250500 µm) producing their own environment and functioning as complex micro-niches
responsive to external environment. They were characterized during the culture(14days to follow ECM modifications) in presence or not of UVA exposure (30 J/cm2,
Xenon Lamp Oriel Solar Simulator). The system was characterized by a quantitativetranscriptomic approach(by NanoStringTM) with a customized codeset containing
49 genes related to ECM remodeling and oxidative stress(OS), and by proteomics
based on high-resolution mass spectrometry, integrated with network analyses(byDionex Ultimate 3000 nLC system and Orbitrap Fusion Tribrid Mass Spectrometer).
At RNA level, in UVA samples, the differentially expressed ECM genes were: HMOX1,
COL4A1, CD44, MME (upregulated) and COL1A1, ELN and COL3A1 (downregulated),suggesting a UVA-induced physiological aging of ECM. 2171 quantified proteins
allowed the in-depth characterization of 3D dermis during growth and differentiation:
UVA dysregulates Oxidative Phosphorylation (mitochondrial functionality), Fibrosis
Signaling Pathway, Glycolysis I and Nrf2-mediated OS Response. Thanks to therelevance of the dermal MPS combined with -omics analyses, it was possible tomirror the cascade of events after UVA exposure and observe the physiologicalrecovery from damage, opening new perspectives in personalized treatments.

LB1757|Late-Breaking ABSTRACTS

The role of cNOS in UV-induced DNA damage and repair
S. Wu1, 4, V. Bahamondes Lorca1, 2, L. Tong1, 3
Edison Biotechnology Institute, Ohio University, Athens, Ohio, United States,2
Tecnología Médica, Universidad de Chile, Santiago de Chile, Chile, 3Nationwide
Children's Hospital, Columbus, Ohio, United States, 4Chemsitry and Biochemistry, Ohio
University, Athens, Ohio, United States

Abstract Body Upon UV exposure, the constitutive nitric oxide synthases (cNOS) are
activated almost immediately and produce chemicals that initiate multiple signaling
pathways that are positively or negatively involved in carcinogenesis. However, therole of cNOS in UV-induced DNA damage and repair is not well elucidated. In thisreport, we demonstrated that UV-induced expression of γH2AX, a marker of DNA
damage and repair, was reduced by treating human keratinocyte cells (HaCaT)
with cNOS selective inhibitor L-NAME or reducing cNOS expression using transienttransfection of cNOS-targeting gRNAs. Furthermore, the overexpression of cNOS in
NOS-null HEK293 cells increases the γH2AX expression level post-UVB exposure
confirming the role of cNOS in the regulation of γH2AX expression upon UVB exposure.
To further analyze the role of cNOS in UVB-induced DNA damage, DNA breakage,and the cyclobutane pyrimidine dimer (CPD) formation were determined. Our data
indicated that DNA breakage analyzed by the Comet Assay and CPD formation
after UVB were reduced by treating the HaCaT cells with L-NAME. Our results alsosuggest that cNOS, through nitric oxide and peroxynitrite production; is involvedin the induction of CPDs at early times after UVB irradiation. Finally, using SKH-1
mouse models, we demonstrated that L-NAME treatment reduced UVB-induced CPD
formation. However, CPD formation was not affected, and DNA repair was impairedby cNOS knockout after UVB exposure. In summary, our data indicated that cNOS
plays important role in regulating DNA damage and repair following UVB irradiation,
which could explain the dual-functional role of cNOS in UVB-induced carcinogenesis.

LB1758Superior germicidal efficacy of 222nm UVC compare to 405nm blue and 635nm red
light in dermatophyte species

Regulation of the independent skin circadian clock by specific opsin using humanskin organotypic culture

K. Kim1, G. Jeong1, H. Choi3, C. Bang2, J. Lee1, 2, Y. Park1, 2, J. Kim4, H. Cho4, H. Oh4,
Y. Kim2
1
Department of Biomedicine & Health Sciences, The Catholic University of Korea,
Seoul, Korea (the Republic of), 2Department of Dermatology, Seoul St. Mary's Hospital,
College of Medicine, The Catholic University of Korea, Seoul, Korea (the Republic of),3
Department of Microbiology, The Catholic University of Korea School of Medicine,
Seoul, Seoul, Korea (the Republic of), 4LG Electronics Inc, Yeongdeungpo-gu, Seoul,
Korea (the Republic of)

M. Bigliardi Qi, S. Lo, E. Bigliardi, S. Park, C. Markale, P. Bigliardi
Dermatology, University of Minnesota Twin Cities, Minneapolis, Minnesota, UnitedStatesAbstract Body Previous research has demonstrated the bactericidal properties of
222nm UVC light against bacteria and viruses, but not against fungi. Our study aims
to compare the germicidal effects of 222nm UVC on various types of dermatophytesthat cause cutaneous fungal infections, with those of conventional laser treatments
and other wavelengths commonly used for tinea treatment, such as 405nm blue
light and 635nm red light. Four species of dermatophytes (Trichophyton erinacei,
Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton tonsurans) were
inoculated onto Potato Dextrose Agar (PDA) plates and incubated at 30°C. We theninvestigated the germicidal effects of 222nm UVC light (500 mJ/cm2), 405nm blue
light (16,380 mJ/cm2), and Lunula laser® (405nm 16,380 mJ/cm2 & 635nm 12,420
mJ/cm2). Subsequently, we compared the colony radius at intervals of 2 to 3 days
for a total of 12 days to evaluate the germicidal effects of each light. 12 days later,
the colony radius decreased in T. mentagrophytes and T.tonsurans with no survivors,
T.rubrum with 42% and T.erinacei with 36% surviving when exposed to 222nm UVC
compared to the control. When exposed to 405 nm blue light alone, only at least 79%
of the cell radius remained alive or did not change. Experiments using the Lunulalaser also showed a minimum of 91% and a maximum of 108% survival. Overall,this experiment demonstrates that 222nm UVC is the most effective light source forsterilizing fungi that cause skin fungal infections. Our results suggest that 222nm
UVC is a more effective treatment for skin fungal infections compared to the 405nm
and 635nm wavelengths traditionally used for treatment.

Abstract Body The circadian clock regulates key physiological processes in theskin, such as differentiation, inflammation in response to external stressors,
while maintaining its health. Light serves as the primary environmental cue
for synchronizing the circadian clock in the skin. Our goal is to understand themechanistic circadian rhythmicity in skin-specific networks independent from central
clock. Different differentiation states of primary keratinocyte mRNA display various
opsin expression patterns, including OPN1, OPN3, OPN5, and peropsin. Peropsin(RRH) is highly expressed in differentiated keratinocytes, detects near-ultraviolet blue
light, and triggers Ca2+ transients. Fully differentiated skin organotypic cultures (OTC)
developed in our lab were exposed to dark and light cycles and exhibited typical clock
gene oscillations comparable to those induced by dexamethasone. Deletion of RRH
in keratinocytes abolishes this light-induced circadian rhythm, suggesting that the
peripheral, light-induced circadian rhythm relies on peropsin activation and blue light.
Bmal1, a key regulator of the circadian clock, was observed to bind to the promoterof various pro-inflammatory cytokines. Some of these cytokines were upregulated
in the epidermis during the dark period of light-synchronized keratinocytes. These
cytokines play a crucial role in regulating skin regeneration and differentiation andare essential in skin disorders such as atopic dermatitis and psoriasis. These findings
are the first to show that the skin's peripheral clock is controlled by specific opsin
and regulates the circadian rhythm, including the inflammation rhythm. This provides
a better understanding of the mechanisms behind skin's independent circadian
regulation in terms of clock genes and signaling pathways. It also revolutionizes ourcomprehension of the pathophysiology of numerous skin disorders with a diurnal
pattern. This knowledge has great potential to improve the efficacy of chronotherapy
and phototherapy.

37

Photobiology

LB1759|Late-Breaking ABSTRACTSLB1760Evaluation of LED irradiation effect to retinol by modified in vitro 3T3 NRU
phototoxicity assay.

Exploration of skin safety according to 222nm and 254nm UVC irradiation in amouse model

S. Lee, S. Cho, J. Cho, S. Kim, S. An
R&I CENTER, Amorepacific Corporation, Yongin-si, Gyeonggi-do, Korea (theRepublic of)

G. Jeong1, K. Kim1, M. Kim1, J. Kim3, H. Cho3, H. Oh3, C. Bang2, Y. Park2, J. Lee2
1
Department of Biomedicine & Health Sciences, The Catholic University of Korea,
Seoul, Korea (the Republic of), 2Department of Dermatology, Seoul St. Mary's Hospital,
College of Medicine, The Catholic University of Korea, Seoul, Korea (the Republic of),3
LG Electronics Inc, Yeongdeungpo-gu, Seoul, Korea (the Republic of)

Abstract Body The COVID-19 pandemic has increased demand for at-home beauty
devices, including LED-irradiated devices known for their effectiveness and ease ofuse in treating various skin conditions. However, concerns have been raised about
the stability and negative effect of cosmetic ingredients used in combination with
LED devices. This study aimed to investigate the phototoxicity of retinol, a commonlyused anti-aging agent, under LED irradiation conditions by modifying the in vitro
3T3 neutral red uptake phototoxicity test (OECD TG 432). To define the irradiationdose which do not cause the cytotoxicity, Balb/c 3T3 fibroblast cells were irradiatedwith blue (470 nm), green (530 nm), and red (635 nm) lights in the 0-64.8 J/cm2
range, independently. Cells were treated with retinol and then irradiated with blue
(6.5 J/cm2), green (27 J/cm2), and red (64.8 J/cm2) lights, respectively. The results
showed that retinol didn't cause phototoxicity under any of the three LED lights (with
PIF<2 and MPE<0.1). These findings suggest that the phototoxic potential of retinol
under blue, green, and red LED lights is very low and consumer will be safely use
the cosmetics containing retinol with LED devices. However, to confirm the safety of
products, beauty devices and its combinations, further investigation is needed caseby case because there are many types of LED devices and products.

LB1761

Abstract Body After the COVID-19 pandemic era with increasing interest in publichealth and hygiene, research has been published testing the relatively safe 222nm
UVC on human subjects. In this study, we evaluated the effects of 222nm UVC
equipment and general 254nm UVC equipment on skin safety and the induction ofother diseases, in accordance with the hazardous chemical concentration standards
recommended by the American Conference of Governmental Industrial Hygienists(ACGIH). Hairless albino mice were exposed to 478mJ/cm2 of 222nm UVC for one
hour or 10mJ/cm2 of 254nm UVC for two minutes and evaluated for three weeks.
Skin and ear thickness changes were observed in both test groups, but recovery
was rapid after the irradiation was discontinued. An increase in epidermal thickness
was observed in the 222nm UVC group, but CPDs positive cells were observedin both groups and recovered over time. In the subsequent study, the distance of
the UVC irradiation device was modified to induce irradiation with 222nm UVC for
approximately 8 hours and 254nm UVC for approximately 2 hours for either one
day or five consecutive days. Consistent with previous studies, both the 222nm and254nm UVC test groups showed mild scaling of the skin and ear thickness changes,
which were observed to rapidly recover after the irradiation was discontinued.
Through these results, it was confirmed that there were mild scaling of the skin andthickness changes during the early stages of UVC irradiation, but rapid recovery wasobserved after the irradiation was discontinued. The study showed that 222nm UVC
and 254nm UVC are safe when tested with low energy output equipment at maximum
recommended exposure levels. Overall, these results support the use of 222nm UVC
for public health and hygiene purposes.

LB1762

Investigating the efficacy of EXC-121 treatment for reversing fibroblast senescenceand improving skin health

A Tropaeoloum majus extract mitigates SASP-related inflammation induced bystress in vitro and in vivo

Y. LeeR&D, EX Healthcare Inc., Seongnam-si, Gyeonggi-do, Korea (the Republic of)

J. Bierman1, L. Vires1, T. L. Laughlin1, H. A. Rovito1, M. L. Hare1, K. U. Miyamoto2,
Y. Xianghong2, J. E. Oblong1
1
The Procter & Gamble Company, Cincinnati, Ohio, United States, 2The Procter &Gamble Company, Kobe, Japan

Abstract Body Skin fibroblast senescence is a significant aspect of the aging process
and has been associated with various age-related pathologies. Understanding themechanisms of fibroblast senescence and finding ways to reverse it are crucial
for promoting healthy aging and improving overall cellular health. Our research
investigates the effects of EXC-121 treatment, a natural compound derived from acomplex screened from hundreds of non-harmful plant extracts, on old fibroblasts. In
this study, we observed that EXC-121 treatment effectively reversed the senescenceof old fibroblasts, as indicated by a decrease in the senescence marker betagalactosidase. Furthermore, EXC-121 treatment showed lower MMP-1 protein
expression levels in UVB-treated human skin fibroblasts, suggesting a protective
effect against UVB-induced skin damage. Additionally, EXC-121 treatment led tohigher COL1 protein expression levels in human skin fibroblasts, indicating a potential
role in promoting collagen synthesis and maintaining skin integrity. Our research
uncovers the potential of EXC-121 treatment in reversing fibroblast senescence andhighlights its positive effects on skin fibroblast health. This study emphasizes theimportance of understanding the underlying molecular mechanisms and exploring
the potential applications of natural compounds in promoting healthy aging andimproving cellular health. In conclusion, our findings suggest that EXC-121 may serve
as a promising treatment for reversing fibroblast senescence and improving skinhealth. Further research is warranted to investigate the mechanisms underlying theaction of EXC-121 and to develop and test novel interventions for promoting healthy
aging and cellular health. The use of natural compounds in skin care and anti-aging
treatments could represent a promising approach to developing safe and effective
therapies that promote overall well-being and longevity.

Abstract Body Inflammaging is an aging hypothesis related to chronic presenceof low inflammation that leads to premature aging by accelerating the skin aging
continuum. Associated mechanisms include inflammation, a secretory phenotype(SASP), and oxidative stress response. Dysfunction at the cellular level ultimately
leads to macro changes that appear as signs of aging. The presented researchstudies the impact of a Tropaeoloum majus extract in response to oxidative
stressors on mitigating inflammatory biomarkers and cellular bioenergetics, Human
keratinocytes were exposed in vitro to UVB and treated with varying concentrations of
T. majus extract and SASP-related inflammatory mediators PGE2, IL-6, and IL-8 were
quantitated. Metabolic flux was measured at 5% and 20% oxygen and H2O2 oxidative
conditions. Cell adhesion was determined by measuring electrical impedance. A
clinical study using a solar simulated radiation exposure protocol to test pretreatment
effects of T. majus in combination with niacinamide to prevent erythema induction.
T. majus extract mitigated UVB induced PGE2, IL-8, and IL-6 levels in keratinocytes.
Cell adhesion measurements showed an increased rate of adherence by the extract.
T. majus extract increased mitochondrial basal rate, maximal respiration, and spare
respiratory capacity. Cell adhesion impedance measurements showed a significant
increase by T. majus extract at a dose response range when compared to media alone.
Pretreatment with a T. majus extract containing formulation showed a significant
effect on mitigating UV-induced erythema. In summary, an extract derived from
Tropaeoloum majus reduced cellular responses to oxidative stress and inflammatorycascades. These findings provide a body of evidence that T. majus extract can
mitigate the skin’s inflammaging condition elicited by environmental stressors such
as UV and can potentially inhibit senescence and premature aging, thereby impacting
skin’s appearance.

38

Photobiology|

Late-Breaking ABSTRACTSLB1763

Combinatorial BRD9 and SMO targeting synergistically suppress UV-induced BCC
tumor burden in a murine model of Gorlin syndrome (GS)A. Kim, Y. Zhu, D. Chen, M. Elmais, M. Athar, D. R. Bickers
Columbia University Irving Medical Center, New York, New York, United States

Abstract Body Hedgehog (Hh)-targeted drugs drive tumor regression in GS patients.
The efficacy of Hh inhibitors (HHi) is limited by tumor resistance/regrowth following
drug discontinuation supporting the need to search for novel druggable treatment
pathways. Bromodomain-containing protein 9 (BRD9) is a component of non-canonicalBAF of SWI/SNF chromatin remodeling complexes. Protein kinase B/AKT enhancescell survival and drives BCC growth. Using murine ASZ001 BCC cells and Ptch1+/-/
SKH1 mice, we show persistent elevation of BRD9 and AKT activity in HHi-resistant
BCC cells and in tumor allografts. Here we test the hypothesis that BRD9 cooperates
with the AKT pathway in driving HHi resistance and assessed the role of BRD9 on
BCC growth. We show that BRD9 physically interacts with and is phosphorylatedby mTOR, a kinase downstream of AKT, and the resulting p-mTOR-BRD9 complexes
are substantially enriched in HHi-resistant cells as well as parental cells carrying
a constitutively activated form of AKT1. These data support the importance ofmTOR in epigenetic regulation of HHi resistance and show that BRD9 is a potential
downstream target of AKT-mTOR signaling. Select BRD9 inhibitors (I-BRD9, BI-9564,
LP99) substantially decrease proliferative capacity and restore vismodegib sensitivity
in BCC cells. In further studies, we evaluated the in vivo efficacy of BRD9 blockade
alone and in combination with vismodegib in chronically UV-irradiated Ptch1+/–/SKH1 mice. After two weeks of treatment with orally administered I-BRD9 or vismodegib(100 mg/kg, daily) microscopic BCC tumor burden was decreased by 30-35%, butwhen used combinatorially resulted in synergistic reduction of tumor burden by >85%
(vs. nontreated, p=0.047). Our data demonstrate the importance of activated BRD9 in
the pathogenesis of BCCs and suggest that combinatorial treatment with BRD9 and
SMO inhibitors could enhance the overall safety and efficacy of currently available
HHIs in GS.

39

Pigmentation & Melanoma

LB1764

The association of adverse childhood experiences (ACEs) with melanoma
B. Montgomery, A. Zheng, K. L. Erickson, J. S. Bordeaux
Dermatology, University Hospitals, Cleveland, Ohio, United States

Abstract Body The relationship between adverse childhood experiences (ACEs) andcancer has been established. The association of ACEs with specific cancers lags.
This study aims to examine (1) the relationship between a person risk of developing
melanoma and their summative ACE score and (2) the relationship between specific
ACEs and one’s risk of developing melanoma. Data was pulled from the 2020 and
2021 CDC Behavioral Risk Factor Surveillance System (BRFFs). Odds ratios (OR) werecomputed to determine the association between ACEs and melanoma. Participants
effected by any ACE had increased odds of reporting a diagnosis of melanoma.
Participants odds did not increase with an increased ACE score. The ACEs with thegreatest odds ratio were as follows: parent that physically hurt participants excluding
spankings (OR 2.41, p<0.0001); live with anyone who was a problem drinker/ alcoholic(OR 2.28, p<0.0001); and was ever touched sexually by an adult or someone 5 years
or older (OR 2.25, p<0.0001). ACEs may increase the odds of developing melanoma
as an adult, especially in those who lived with a problem drinker or victims ofchildhood sexual and/or physical abuse. The ACE questionnaire is easy to administerin clinic and may help identify patients with increased odds of developing melanoma.
Additional studies are necessary to further examine the association of ACEs andmelanoma to determine its merit as a risk factor for melanoma.

LB1766

Notch signaling regulates melanogenesis in melanocytes|

Late-Breaking ABSTRACTSLB1765An open-label bilateral-comparison clinical trial testing the safety and efficacy ofruboxistaurin gel on solar lentigos
E. Taylor1, D. E. Zepeda Reyes2, M. Wong1, N. Eliovits1, J. Sanchez Lopez2,
K. M. Parada Cunza2, K. Beutner1
1
DermBiont, Inc., Boston, Massachusetts, United States, 2Zepeda Dermatologia, Santa
Tecla, La Libertad, El Salvador

Abstract Body Disorders of hyperpigmentation, such as solar lentigos, are caused by
focal overproduction of melanin. Tyrosinase, the key enzyme in the melanin synthetic
pathway, requires phosphorylation by PKC-β for activity. Ruboxistaurin is a potent
and selective inhibitor of PKC-β. This is an open-label bilateral-comparison clinical
trial exploring the safety and efficacy of ruboxistaurin, to inhibit melanogenesis insolar lentigos. Fifteen healthy subjects with 4 targeted solar lentigos on one dorsal
hand and a comparable contralateral area with untreated lentigos were enrolled.
Subjects applied ruboxistaurin gel 0.8% BID for 12 weeks to one dorsal hand with thecontralateral hand being the untreated control. All treated sites were scored using
both colorimetry and with the Investigator Dynamic Global Assessment (IDGA), which
compares relative pigmentation of the treated areas to untreated areas. Tolerability
was evaluated through assessment of local signs and symptoms (pain/burning/
stinging, pruritus, erythema, edema, erosion/ulceration, lichenification, exudation, anddesquamation) at the dorsal hand treatment site. On the dorsal hand with the treatedlentigos, 100% of subjects (n=15) achieved either an IDGA of –2 (moderately lesspigment) or –1 (slightly less pigment) with 27% (n=4) achieving an IDGA of –2. There
was also a statistically significant difference between the change in colorimetry fromscreening readings (p<0.0001) between treated and untreated lentigos at Week 12.
The treatment was well tolerated with no serious adverse events, and most (99%)
observations had no local tolerability reactions. This trial demonstrates that topicalruboxistaurin gel 0.8%, a PKC-β inhibitor, is well tolerated and reduces melanin
production in solar lentigos. Ruboxistaurin has the potential to be a new treatment
option for solar lentigos and other disorders of hyperpigmentation such as melasma.

LB1767

Fibroblast growth factor-2 (FGF-2) promotes melanocyte proliferation in humanepithelial cell culture

L. Pan3, B. Tandukar3, S. Joshi3, E. U. Kalapurakal3, T. J. Hornyak1, 2, 3
Research & Development Service, VA Maryland Health Care System, Baltimore,
Maryland, United States, 2Department of Dermatology, University of Maryland Schoolof Medicine, Baltimore, Maryland, United States, 3Department of Biochemistry andMolecular Biology, University of Maryland School of Medicine, Baltimore, Maryland,
United States

K. Ferland1, 2, 3, B. Magne1, 2, 3, D. Larouche1, 2, 3, L. Germain1, 2, 3
1
Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX,
Quebec, Quebec, Canada, 2Centre de recherche du CHU de Quebec-Universite Laval,
Quebec, Quebec, Canada, 3Surgery, Universite Laval, Quebec, Quebec, Canada

Abstract Body Notch signaling is an evolutionarily-conserved mechanism thatcan regulate multiple development processes including cell proliferation, celldifferentiation and stem cell maintenance. Unlike many developmental signaling
pathways, Notch signaling is dependent upon cell-cell interaction through binding
events of transmembrane ligands and receptors on juxtaposed cells. Although theimportance of Notch signaling in melanoblasts and melanocyte stem cell (McSC)
maintenance has been documented, the effect of Notch signaling in differentiatedmelanocytes is still not fully understood. Here, we observed Notch signaling,
determined by nuclear presence of Notch intracellular domain 1 (NICD1), was active
in bulge and outer root sheath (ORS) melanocytes during hair follicle (HF) anagen,but was not detected in telogen McSCs, indicating selective Notch activation inmelanocytes during anagen. Notch inhibition by the Notch gamma-secretaseinhibitors DAPT and DBZ reduced melanin synthesis in differentiating primary CD34McSCs and the immortalized murine melanocyte cell line melan-a, while Notch
activation driven by overexpression of NICD1 and NICD2 induced melanin synthesis inmelan-a cells by inducing the expression of the melanogenic enzymes Tyr, Tyrp1, andDct. However, CRISPR-mediated knockout of the canonical Notch signaling mediator
RBP-J in melan-a cells inhibited cell growth but did not diminish melanogenesis. Ourfindings indicate that Notch signaling is required for melanogenesis independent of
RBP-J transmission of Notch activity.

Abstract Body Severe burn patients in lack of donor sites for autograft harvesting
can be treated with self-assembled skin substitutes (SASSs) produced in ourlaboratory from a small patient's skin biopsy. However, patient's pigmentation is
not fully restored after SASS grafting, resulting in local pigmentation defects. Thesepigmentation defects are likely caused by the dilution of melanocytes in epithelial
cell cultures that are used to produce the epidermal part of SASSs. Here, wehypothesized that the supplementation of the SASS culture medium with Fibroblast
Growth Factor-2 (FGF-2), a melanogenic physiological growth factor, could increasemelanocyte proliferation and eventually improve SASSs pigmentation. We firstevaluated the role of FGF-2 in a dose-dependent manner on melanocyte proliferation
using proliferation assay. We then evaluated by ELISA whether keratinocytes
cultured in our culture conditions secrete FGF-2. Then, we evaluated the effect of
FGF-2 on melanocyte proliferation in epithelial cell cultures containing, among
others, keratinocytes and melanocytes, using flow cytometry. Our results show that
FGF-2 promotes melanocyte proliferation at an optimal dose of 0,2nM. Our results
also suggest that FGF-2 secretion by keratinocyte could be neglected, as they do
not secrete a high dose of FGF-2. Moreover, the optimal dose of 0,2nM FGF-2 also
promoted melanocyte proliferation in epithelial cell culture. These results suggestthat FGF-2 could be used to improve SASS pigmentation. Future experiments will
aim to evaluate pigmentation of SASSs with epithelial cells cultured in the presenceof FGF-2. Hopefully, pigmentation protection will be restored when FGF-2 is added to
SASS by promoting melanocyte proliferation.

140

Skin of Color

LB1768

LB1769Y. Arbel1, Y. Arbel2, A. Kerner3, M. Kerner4, 5
1
Economics and Management, Western Galilee College, Akko, Israel, 2Mathematics,
Bar Ilan University, Ramat Gan, Israel, 3Netanya Academic College, Netanya, Israel,
4
Medicine, Technion Israel Institute of Technology, Haifa, Israel, 5Dermatology, Emek
Medical Center, Afula, Northern, Israel

1

Is obesity a risk factor for melanoma? (The manuscript was recently published in
BMC Cancer and is available in the following link: https://bmccancer.biomedcentral.
com/articles/10.1186/s12885-023-10560-8)

Abstract Body Objectives: Are twofold: 1) to estimate the relationship between obesity(BMI ≥30) and the prevalence of melanoma in different US states and 2) to examine
the possibility of defining a new risk group. This might enhance the possibility ofdetection, which in turn, might increase the survival rates of patients. Study design:
A cohort Study, based on data at the US statewide level in 2011–2017, where thedependent variable (the annual new melanoma cases per 100,000 persons) is adjusted
for age. Method: Quadratic regression analysis. This model permits a non-monotonic
variation of obesity with new melanoma cases adjusted for age, where the control
variable is the level of UV radiation. Results: Demonstrate a negative correlation
between obesity and incidence of melanoma. This outcome is further corroborated
for Caucasians. Conclusions: We should continue to establish primary preventionof melanoma by raising photo protection awareness and secondary prevention bypromoting skin screening (by physician or self ) among the entire population groupin all BMI ranges. Advanced secondary melanoma prevention including noninvasive
diagnosis strategies including total body photography, confocal microscopy, AI
strategies should focus the high-risk sub group of Caucasians with BMI < 30.

LB1770

Disparities in state medicaid coverage of tretinoin for pigmentary disorders
compared to acne vulgaris
P. Manjaly1, K. Kamal1, S. Ly1, K. Sanchez1, E. Getachew2, A. Mostaghimi1,
N. Theodosakis2
1
Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, United States,2
Dermatology, Massachusetts General Hospital, Boston, Massachusetts, United States

Abstract Body Melasma and post-inflammatory hyperpigmentation (PIH) arecommon dermatologic conditions that disproportionately affect patients with skinphototypes III-VI. Tretinoin is a first-line agent for treating both pigmentary disorders
and acne. Comparing treatment coverage for tretinoin between these two common
diseases with similar appearance-related morbidity may highlight disparities ininsurance coverage for diseases that primarily affect patients of color. The primaryobjective of this investigation was to determine the extent of Medicaid coverage oftretinoin for melasma and PIH compared to acne vulgaris in the United States. We
conducted a cross-sectional study of Medicaid insurance plans in 50 states andthe District of Columbia from February 1-28, 2023. Data was collected from online
publicly available preferred drug lists, prior authorization criteria, and via email or
telephone inquiries with state Medicaid offices. Information collected included
coverage restrictions, such as age restrictions, diagnostic restrictions, preferred drug
status, and prior authorization requirements. Complete coverage data for all threeclinical indications was retrieved from 30 (58.8%) states; partial coverage data foracne vulgaris was retrieved from an additional 16 (31.4%) states; no coverage data
was retrieved from 5 (9.8%) states. Of states reporting coverage data, topical tretinoin
is covered in 45 (97.8%) states for acne vulgaris and 10 (33.3%) states for melasma
and PIH. Melasma and PIH were less likely to be covered by Medicaid compared toacne vulgaris (p < 0.05). Our results show that there is significantly greater insurance
coverage for acne vulgaris compared to pigmentary disorders despite their similar
morbidity profiles. Given that pigmentary disorders disproportionately affect patientsof color, greater advocacy is required to ensure equal treatment for conditions that
disproportionately impact racial minority patients.

|

Late-Breaking ABSTRACTS

Do high-rise buildings influence melanoma? Tall buildings as positive externalities(The manuscript was recently published in the academic journal "Cities" and isavailable in the following link: https://www.sciencedirect.com/science/article/abs/
pii/S0264275122004413).
Y. Arbel1, Y. Arbel2, A. Kerner3, M. Kerner4, 5Western Galilee College, Akko, Israel, 2Mathematics, Bar Ilan University, Ramat
Gan, Israel, 3Netanya Academic College, Netanya, Israel, 4Technion Israel Institute ofTechnology The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel, 5Emek
Medical Center, Afula, Northern, Israel

Abstract Body Population growth, urban densification and shortage of available
land make the construction of tall buildings increasingly prevalent. Given the world
population growth, the volume of high-rise construction is steadily rising. Previous
literature identifies skyscrapers as a potential source of negative externalities dueto their high carbon footprints, and negative environmental features (reduction of
sun light and wind-tunnel effects). The current study is the first to provide evidence
supporting the notion that skyscrapers may also be considered a source of a positive
externality. Based on data from 50 US states over a 19-year period (1999–2017), we
demonstrate projected connection between the prevalence of melanoma and highrise construction per state. This result might be attributed to the shadier environment
created by these structures. Findings suggest that the annual projected increase inmelanoma cases may be offset by approximately 53 additional high-rise buildings
per state. Research findings may be of assistance to city planner. Potential saving
associated with reduction of melanoma prevalence in terms of lost productivity andlife lost should be considered. In addition, Caucasians with above 50 nevi as well as
those with a personal or family history of melanoma should be encouraged to live inurban environments with tall buildings.

LB1771

miR-4521 regulates the autophagic pathway in keratinocytes
H. Maeno1, Y. Suzuki-Horiuchi1, A. Funakoshi2, Y. Sato2, T. Ishii2, J. T. Seykora1
Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, United States,2
Basic Research Development Division, Rohto Seiyaku Kabushiki Kaisha, Kizugawa,
Kyoto, Japan
1

Abstract Body Previously, we reported that expression of miR-4521 was upregulated
in human lentigos using microarray high thorough-put screening. Our prior work
indicated that miR-4521 downregulates mRNA and protein levels of FOXM1 andGABARAPL2. To better understand the biological impact of mir4521 downregulates
mRNAs in keratinocytes, we performed bulk RNA sequencing of transient express
miR-4521 HaCaT cells. FoxM1, a known miR-4521 target, mRNA counts wasdecreased to 66.41% to its control (padj <0.005). GSE analysis showed that Hallmarkof G-M checkpoint and E-F target signaling signature pathways were downregulated
in the miR4521 transfected cells. These data support the deceased cell growth of
mir4521 transfected cells compared to that of control cells. We have shown miR4521 transient expressing HaCaT cells down regulated the canonical autophagy
component, such as GABARAPL2 gene (at mRNA and protein levels). Regarding
expression of additional genes in the autophagy pathway, there was significant
downregulation of GABRAP, GABARAPL2, ATG4C, ATG5, ATG7 mRNA (padj <0.005).
However, there was upregulation of PRKAA1, BECN1 and GARAPL1 mRNAs (padj<0.005) . Further studies of the mir4521-transfected HaCaT cells revealed an
accentuated autophagy flux (higher levels of LC3B-II) post stimulation with H2O2,
rapamycin and melanosomes. These data suggest that miR-4521 may represent atarget to regulate autophagy in keratinocytes, including autophagy of melanosomes.

41

Skin of Color|

Late-Breaking ABSTRACTSLB1772

Melanoma risk in skin of color patients with a history of keratinocyte carcinoma
C. Mohr, Y. Li, L. Navsaria, C. Hinkston, D. Margolis, M. Wehner
Health Services Research, The University of Texas MD Anderson Cancer Center,
Houston, Texas, United States

Abstract Body Our study aimed to explore the absolute and relative risks of melanoma
in patients with history of keratinocyte carcinoma (KC), evaluating patients withskin of color specifically, which has not previously been done. We performed a
retrospective cohort study using a de-identified, random sample of 4,999,999 feefor-service Medicare beneficiaries aged ≥65 years (2009-2018). We included skin ofcolor patients with a treated KC and, as a comparator group, skin of color patientswith the benign lesion seborrheic keratosis (SK). Both groups required at least 1 year
between dataset entry and the first KC or SK diagnosis. We excluded patients witha history of HIV, organ transplant, or prior skin cancer. We evaluated absolute risksof melanoma over time in skin of color patients with KC. We also compared skincancer risks in skin of color patients with KC to skin of color patients with SKs using
a competing risks regression (competing risk of death, adjusted for age, gender, UV
index, history of actinic keratosis, and dermatology visits). We evaluated a total of
3,284 skin of color patients with KC and 57,557 skin of color patients with SKs who
met inclusion criteria, with a mean follow-up of 3.9 (SD 2.6) and 4 (SD 2.7) years,
respectively. The absolute risk of melanoma for skin of color patients with a historyof KC was 0.89% (95% CI 0.56%-1.37%) at 5 years after KC. Skin of color patientswith KC were at significantly increased risk of melanoma compared with skin of color
patients with SK (adjusted hazard ratio (HR) 2.09, 95% CI 1.37-3.18). Patients withskin of color are often excluded from skin cancer literature despite studies findingthat this population is more likely to die from melanoma. A history of KC puts skin ofcolor patients at increased risk of melanoma, though the absolute risks of melanoma
in this group are still modest.

42

Skin, Appendages, and Stem Cell Biology

LB1773

Dutasteride in the treatment of frontal fibrosing alopecia: Systematic review andmeta-analysis
H. Seo1, 2, S. Kim1, J. Park1, S. Oh1, J. Kim1
Dermatology, Hanyang University Guri Hospital, Guri, Korea (the Republic of), 2Hanyang
Institute of Bioscience and Biotechnology, Hanyang University, Seongdong-gu, Seoul,
Korea (the Republic of)1

Abstract Body Background: Frontal fibrosing alopecia (FFA) is a type of scarring
alopecia characterized by fronto-temporo-parietal hairline recession which is mostly
seen in postmenopausal women. Although no proven treatment for FFA exists,
dutasteride has been suggested as a potential treatment option. Methods: Systematic
search was performed from inception to 18 August 2022 using PubMed, Embase,Medline, Web of Science, and Scopus. According to the Preferred Reporting Items
for Systematic Reviews and Meta-analysis 2020 criteria, identification and selectionof the studies was conducted. Meta-analysis was performed for the effectivenessof dutasteride on FFA. Results: There were total 7 articles and 361 patients who
administered oral dutasteride through literature screening. The majority of patientsin these studies received adjuvant therapies along with dutasteride, mainly topical or
intralesional corticosteroids. Estimated proportion of stabilization of frontal fibrosing
alopecia with oral dutasteride was 0.639 (95% CI: 0.405~0.873). In addition, when
performing subgroup analysis of patient with improvement, estimated proportionof improvement was 0.356 (95% CI: 0.163~0.549). This study showed that 192/361(53.2%) patients had achieved stabilization or improvement and 36/88 (40.9%)
patients had improved of FFA after using dutasteride. In the individual studies, actual
proportion of stabilization ranged from 26.3% to 100% and improvement ranged from
15.3% to 45.6%. Conclusions: This study suggested that oral dutasteride in patientswith FFA is a good treatment option for disease stabilization or improvement. Further
randomized, double-blind, placebo-controlled study would strengthen the role ofdutasteride as part of possible treatment of choice for FFA.

LB1775|Late-Breaking ABSTRACTSLB1774

Establishing competent morphogenetic fields for tissue pattern regeneration in skinorganoids
M. Lei1, J. Jiang1, W. Wu1, M. Wang1, J. Zhang1, Y. Lai2, H. Harn3, L. Yang1, C. Chuong3
1
Bioengineering, Chongqing University, Chongqing, China, 2Integrative Stem Cell Center,
China Medical University Hospital, Taichung, Taiwan, 3Department of Pathology,
University of Southern California, Los Angeles, California, United States

Abstract Body The formation of tissue patterns is critical for organ functions indevelopment and regeneration. Tissue patterning is a fundamental process that
occurs in developing skin and in wound-induced hair neogenesis. Recent works show
tissue patterns can also be produced in organoids. To advance the use of organoids
for organ regeneration, we learn principles that govern the skin organoids toregenerate hairs. We show the formation of epidermal-dermal coupled cysts function
as competent morphogenetic units (CMU) which harbor the ability of skin organoids
to regenerate. ScRNA-sequencing shows the emergence of cell types and new cellinteractions during CMU formation. In newborn skin organoids, epidermal cells
undergo apical-basal polarization via the IFNr-PKR-PKC signaling module. DermalTgfb regulates Gsk3 to establish basement membranes between the epidermal cyst
and dermal cells. Meanwhile, VEGF signaling mediates dermal cell attachment tothe cyst. Adult cells cannot form organoids but can be induced to generate CMUs
and regenerate hairs by adding IFNr or VEGF. We compare the similar principles anddifferent paths used to establish morphogenetic competency in developing skin,wound-induced hair neogenesis, and organoids.

LB1776

Enlightening the role of iron overload in the development of cutaneous
lipodermatosclerosis

Optimized culture conditions of hidradenitis suppurativa skin for preclinicalscreening ex vivo

M. Torregrossa, J. Simon, S. Franz
Universitat Leipzig, Leipzig, Sachsen, Germany

J. R. Viola1, M. Fehrholz1, K. I. Pappelbaum1, T. Bíró1, T. Meyer2, F. Bechara2,
S. Schneider-Burrus3, R. Paus1, J. Edelkamp1, M. Bertolini1
1
Monasterium Laboratory Skin & Hair Research Solutions GmbH, Munster, NordrheinWestfalen, Germany, 2Klinik für Dermatologie, St. Josef Hospital,, Bochum, Germany,
3
Center for Dermatosurgery, Havelklinik, Berlin, Germany

Abstract Body Our study aims to investigate the pathogenic effects of iron overloadin the skin of patients with chronic venous insufficiency (CVI), focusing on theunderlying molecular mechanisms contributing to disease progression. Whileprevious studies have examined the clinical aspects of CVI and lipodermatosclerosis(LDS), the molecular impact of iron on skin cells leading to LDS remain unclear. To
address this gap, we employed in vitro and in vivo approaches. In biopsies from
CVI patients, erythrocytes were observed in the dermis and hypodermis, alongwith siderophages (macrophages phagocyting erythrocytes), indicating a role ofmacrophages in erythrocyte clearance. We then demonstrated, that macrophages
exposed to erythrocytes and iron in long-term acquire a pro-inflammatory phenotype,
resulting in an inflammatory state in the skin. To investigate the effects of ironoverload in vivo, we generated a mouse model that mimicked the local iron overloadin skin as observed in CVI patients. The model exhibited an iron-overloaded adipose
layer and adipocyte lipolysis, leading to adipocytes’ activation and release of
adipokines, inflammatory cytokines, and chemokines. These events result in the
recruitment of monocytes and macrophages with an inflammatory phenotype. We
also observed reduced adipocyte differentiation and number, likely due to repressionof Wnt signaling, downregulation of pro-differentiation and pro-adipogenesis genes
and a decrease in adipose stem cells in the iron overloaded skin tissue. Moreover,the inflammatory state propagated into the dermis, resulting in resident macrophageactivation, fibroblast hyperproliferation and reduced extracellular matrix deposition.
In summary, this study provides insights into the molecular mechanisms underlying
LDS progression in CVI patients with iron overload. Our findings suggest that ironoverload in the skin induces an inflammatory state that originates in the adipose
layer and propagates to the dermis, affecting resident macrophages, adipocytes andfibroblasts' activation and phenotype.

Abstract Body Hidradenitis suppurativa (HS) is a chronic progressive skin disorderwith multifactorial aetiology and an intricate inflammatory phenotype. The few
described HS skin organ culture assays are poorly characterized. Therefore, we
aimed at standardizing the HS skin organ culture to use it as preclinical screening
tool. Full-thickness lesional (nodule- or fistula-containing) and peri-lesional samples
from HS patients were cultured for 24, 48h or 72h. RNAseq analysis of peri-lesional
vs fistula-containing HS samples for 24h with vehicle control or adalimumab, an
α-TNFα antibody, showed reduced expression of HS-relevant genes: alarmins andantimicrobial peptides (S100A7A/A9, CAMP, DEFB4A), Lipocalin2 (LCN2) and IL17C.
Since tissue integrity was lost after 48h in standard culture medium, we assessed theeffect of different culture conditions for 24, 48 and 72h in comparison to non-cultured
HS samples to optimize the culture period in order to preserve the disease phenotype.
HS-associated immune phenotype markers (CD3, CD66b, CD19) and disease activity
markers (Krt15, Krt17, LCN2), analyzed by immunofluorescence as well as CCL20
release into the medium, assessed by ELISA, were preserved over 72h in a defined,
standardized, serum-supplemented proprietary medium. An initial period of serum
starvation did neither impair skin integrity nor HS phenotype, providing a therapeutic
window in which biologics/drugs can be administered without serum. Our optimized
HS organ-culture assay is ideal for multi-omics analyses, to assess novel candidate
HS therapeutics ex vivo, to identify biomarkers, and to dissect underlying mechanismof HS pathogenesis.

43

Skin, Appendages, and Stem Cell Biology

LB1777

A novel ex vivo model of human hair follicle immune privilege collapse reveals thepotential of farudodstat, a DHODH inhibitor, as a therapeutic for alopecia areata
treatment
T. Rouillé1, S. Barbosa1, A. Steinhoff1, I. Piccini1, J. Edelkamp1, F. Cevikbas2,
M. Bertolini1
1
Monasterium Laboratory Skin & Hair Research Solutions GmbH, Munster, NordrheinWestfalen, Germany, 2ASLAN Pharmaceuticals, San Mateo, California, United States

Abstract Body Alopecia areata (AA) is an inflammatory disorder of the hair follicles(HF) characterized by increased IFNγ levels, immune privilege (IP) collapse, and a
Th1-mediated inflammatory response towards the hair bulb leading to prematurecatagen development, HF dystrophy and hair loss. Dihydroorotate dehydrogenase(DHODH) plays a key role in T-cell proliferation and its inhibition decreases Th1cell differentiation and IFNγ production. In this study, we investigated whether
farudodstat, a DHODH inhibitor, could be beneficial for the treatment of AA by meansof an innovative model in which healthy human microdissected HFs were stimulatedwith anti-CD3/CD28 antibodies to promote intra- and peri-follicular T-cell activation
via the T-cell receptor (TCR). The experimentally induced TCR stimulation ex vivo
resulted in increased numbers of proliferative T-cell indicated by positive CD3+ andCD3+Ki-67+ cells in the HF epithelium and mesenchyme. Importantly, the expressionof MHC I and II was significantly increased in the bulb epithelium and mesenchymeof anagen HFs stimulated with anti-CD3/CD28 antibodies, indicating loss of IP
following T-cell activation. Treatment with 140 nM farudodstat significantly reduced
the proliferation of T-cells, abrogated MHC protein expression, and also reduced thenumber of MHC II+ cells in the hair bulb. Of note, farudodstat treatment alone did notpromote catagen induction and did not affect hair matrix keratinocyte proliferation
or IP markers, suggesting no signs of cytotoxicity in healthy microdissected HFs.
Our preliminary results show that T-cell activation via anti-CD3/CD28 treatment in
the ex vivo model can successfully induce key features of AA including IP collapse.
Additionally, our data suggest that the DHODH inhibitor farudodstat may protect fromIP collapse and offer a novel therapy for AA.

LB1779Optimization of RDEB patient-derived induced pluripotent stem cell (iPSC)
differentiation into keratinocytes and fibroblasts
N. T. del Agua1, 4, H. Cheng2, Y. Hong2, J. A. McGrath2, 5, C. Hsu1, 4, 2, C. Huang3
Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan,
2
National Cheng Kung University Department of Dermatology, Tainan, Taiwan,
3
Department of Medical Laboratory Science and Biotechnology, National Cheng Kung
University College of Medicine, Tainan, Taiwan, 4International Center for Wound Repair
and Regeneration, National Cheng Kung University, Tainan, Taiwan, 5St. John's Instituteof Dermatology, King's College London, London, England, United Kingdom|

Late-Breaking ABSTRACTSLB1778Wound closure in diabetic db/db mice is facilitated by autologous hair-follicle
associated pluripotent (HAP)stem cells
A. Hasegawa1, 2, K. Obara2, N. Takaoka1, K. Shirai2, Y. Hamada2, N. Arakawa2, R. Aki2,
R. Hoffman3, 4, Y. Amoh2
1
Dermatology, Kitasato University Graduate School of Medical Science, Sagamihara,
Kanagawa, Japan, 2Dermatology, Kitasato Daigaku Igakubu, Sagamihara, Kanagawa,Japan, 3Anti Cancer Inc, San Diego, California, United States, 4Surgery, University ofCalifornia San Diego, La Jolla, California, United States

Abstract Body Wounds in diabetic patients are often difficult to heal (refractorywounds), leading to infection and necrosis, requiring to skin graft surgery or lower
extremity amputation. Hair-follicle-associated pluripotent (HAP) stem cells arelocated in the bulge area of the hair follicle. HAP stem cells can differentiate into
keratinocytes, vascular endothelial cells, cardiomyocytes, neurons, pigment cells,smooth muscle cells, and glial cells. HAP stem cells are readily accessible to everyone,
and can be used for autologous transplantation without immunosuppression, do
not form tumors, and can be cryopreserved without loss of pluripotency, and arebankable. HAP stem cell sheets are formed by culturing the upper part of the hairfollicle containing the hair follicle stem cell region. In the present study, we developed
autologous stem cell sheets for rapid wound healing in diabetic db/db mouse models.
The whisker pad from the upper lip of db/db mice was harvested and the upper partsof the whisker hair follicles were cultured in medium for 4 weeks to generate HAP
stem cell sheets. The HAP stem cell sheets were transplanted into 10 mm circular
full thickness excisional wounds established on the back of db/db mice. The wound
was regularly photographed, and the size of the wound was measured daily. After 14days, tissue was collected from the wound site and the wound healing efficacy of
HAP stem cell sheet transplantation was demonstrated. The present results suggest
autologous HAP stem cells can be used to heal refractory diabetic ulcers.

LB1780Transcriptomic profiling of laser captured suprabulbar outer root sheath reveals
genes involved in immune privilege and inflammatory response by dandruff hairfollicles

1

S. Limbu1, T. Purba1, R. K. Bhogal2, R. Paus1, 3, 4
1
The University of Manchester Faculty of Biology Medicine and Health, Manchester,Manchester, United Kingdom, 2Unilever R&D Colworth, Bedford, United Kingdom,
3
Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami
School of Medicine, Miami, Florida, United States, 4Monasterium Laboratory Skin & Hair
Research Solutions GmbH, Munster, Nordrhein-Westfalen, Germany

Abstract Body Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic
skin blistering disease caused by pathogenic variants in the COL7A1 gene whichcodes for type VII collagen (C7). Alterations in this gene result in poor anchoring fibrils
causing the epidermis to detach easily from the dermis. Clinically, the manifestations
as repetitive skin blistering and scarring. To improve clinical care, interventions
aimed at restoring C7 function are necessary, and one potential approach is throughcell therapy. Peripheral blood mononuclear cells (PBMCs) obtained from an RDEB
patient with a homozygous COL7A1 c.1573C>T p.Arg525Ter nonsense variant
were reprogrammed into induced pluripotent stem cells (iPSCs) and differentiatedinto epidermal and dermal cells. In contrast to traditional differentiation protocols
that employ embryoid bodies formed using hanging drop or microwell plates, we
discovered that initiating the process with monolayer cell populations significantly
enhances the efficiency of generating epidermal and dermal cells. This optimized
method demands a lower seeding density (<5x105 cells), reduces the necessity for
multiple plate coatings, and accelerates the completion of the differentiation process.
Gene-corrected RDEB-iPSCs will be generated, and the subsequent differentiatedcells will be used for the development of skin substitutes and cell infusions. These
innovations will first be tested in preclinical animal studies before advancing towardclinical application.

Abstract Body Dandruff is characterized by flaking, itchiness, and mild inflammation,and occurs on the scalp where there is an abundance of hair follicles (HF). The HF
has immune privilege (IP) which involves active mechanisms to inhibit inflammationand promote immune tolerance. We have recently found that there is weakeningof HF IP in the suprabulbar outer root sheath (ORS) in dandruff as elucidated via
in situ protein expression analyses of IP markers (in preparation for submission).
However, it is unknown whether gene expression patterns within this compartment in
dandruff scalp show any changes that might be similarly reflective of this weakened
IP phenotype. We therefore performed RNA-Seq using laser captured tissue obtained
specifically from the suprabulbar ORS, comparing healthy versus dandruff HFs(lesional and non-lesional, N=4 patients). We conducted differential gene expression
analysis to observe the expression levels between the comparison groups. We founda total of 115 differentially regulated genes in lesional versus healthy ORS, 715 inlesional versus non lesional ORS and 93 in non-lesional versus healthy ORS (p-value<0.01, fold change 1.5). Next, we undertook bioinformatics comparison using
QIAGEN ingenuity pathway. In lesional and non-lesional compared to healthy ORS
analysis revealed changes in genes involved in immune response and inflammatory
canonical pathway, in particularly genes involved in immune privilege (p-value <0.01),
while in lesional versus non-lesional ORS, genes are involved in the hair growth
cycle pathway. Our data suggests that the suprabulbar ORS have changes in genes
involved in immune privilege and may contribute towards the inflammatory responsein dandruff.

44

Skin, Appendages, and Stem Cell Biology|

Late-Breaking ABSTRACTSLB1781

LB1782A. R. Foster1, C. Admane1, F. Torabi1, H. Gopee2, N. Huang1, K. Koehler3, L. Gambardella1,
M. Haniffa1
1
Wellcome Sanger Institute, Hinxton, Cambridgeshire, United Kingdom, 2Newcastle
University Biosciences Institute, Newcastle upon Tyne, Newcastle upon Tyne, United
Kingdom, 3Boston Children's Hospital, Boston, Massachusetts, United States

C. Pan1, 2, 3, X. Wang1, 2, 3, Z. Yao1, 2, 3, M. Li4
Dermatology Center, Xinhua Hospital, Shanghai Jiao Tong University School of
Medicine, Shanghai, China, 2Department of Dermatology, Xinhua Hospital, School of
Medicine, Shanghai Jiao Tong University, Shanghai, China, 3Institute of Dermatology,
Shanghai Jiao Tong University School of Medicine, Shanghai, China, 4Department of
Dermatology, Children’s Hospital of Fudan University, Shanghai, China

Investigating macrophage and endothelial cell interaction using iPSC-derived skinorganoid model

Abstract Body Modeling human skin as a multicellular organ with appendage
structures has huge potential for advancing translational dermatology researchand clinical application. Hair-bearing skin organoids(SkO) generated from humaninduced pluripotent stem cells (iPSC) are a complex model that meets many of theserequirements. However, one limitation of this model is the lack of immune cells.
We as well as others have generated single cell RNAseq and spatial transcriptomic
datasets to thoroughly characterize human skin cell populations across lifespan. We
have used these datasets to compare the dynamic tempo and stages of iPS-derived
SkO differentiation in comparison to human prenatal and adult skin. Our analysis
shows that cell states of SkO at 4 weeks and 19 weeks in culture align with prenatalskin at 7 PCW and adult skin respectively revealing the accelerated tempo of SkO
differentiation. scRNAseq analysis highlighted paucity and limited heterogeneity ofendothelial cells in SkO compared to prenatal skin as SkO only contained capillaryarteriole cells. We hypothesized that the lack of immune cells in SkO could explain
the reduced heterogeneity of endothelial cells compared to fetal skin. Co-culture ofmacrophages and endothelial cells, both derived from Kolf2s.1 iPSCs, demonstrated
that the presence of macrophages significantly increased endothelial cell sprouting
and subsequent network formation in angiogenesis assays. Co-culture of SkO withmacrophages improved SkO blood vessel formation. Overall, we demonstrated thatthe role of macrophages in the guidance of endothelial tip cell during angiogenesis
is key to the development of complex vasculature network in human SkOs, whichsuggests a vital role of macrophages in skin morphogenesis. In addition, we
demonstrated that the SkO model is excellent to study cell-cell interaction during skindevelopment and we predict it will be key for translational research in dermatology
and beyond.

A new gene ADAM17 for the autosomal dominant inheritance of hypotrichosis

1

Abstract Body Hereditary hair loss in human is a group of clinically and geneticallyheterogeneous disorders. It is characterized by sparse to complete absence of hairon the scalp and other body parts. We identified a new pathogenic gene (ADAM17)and its mutation site associated with hereditary hypotrichosis with woolly hairfor the first time. By studying the affected family and ADAM17-mutation knockin mice, we found that ADAM17 plays an important role in hair follicle stem cells.
ADAM17 mutation leads to the depletion of hair follicle stem cells, abnormal hairfollicle structure and sparse hair. Furthermore, mutations in the ADAM17 gene result
in decreased expression of proteins instead of transcriptional levels, increased
ubiquitination levels, and significant downregulation of the Notch signaling pathway.
Based on these findings, we hypothesize that the ADAM17-Notch signaling axis
regulates hair follicle stem cell development and that mutations in the ADAM17
gene mediate self-ubiquitination and proteasomal degradation, ultimately leading tohair loss and regeneration disorders. This study aims to elucidate the mechanismof ADAM17-Notch signaling axis regulation in hair follicle development, providing
potential targets for clinical diagnosis and treatment of hair loss.

LB1783

Genetic and epigenetic regulation of HES1 and KLF6 in skin aging: Results from alarge population-based study in China
B. Li1, 2, S. Tian2, F. Wang3, 4, W. Su3, 4, S. Wang2
Department of Skin and Cosmetics Research, Shanghai Skin Disease Hospital,
Shanghai, China, 2CAS Key Laboratory of Computational Biology, Shanghai Institute of
Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of
Sciences, Shanghai, China, 3Yunnan Botanee Bio-technology Group Co., Ltd., Yunnan,
China, 4Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan,
China1

Abstract Body A previous study, based on human single-cell RNA sequencing dataand cellular and mice models, has shown that HES1 and KLF6 are driver genes ofskin aging, exerting geroprotective effects. To evaluate whether there are genetic andepigenetic risk factors linked to skin aging mediated by HES1 and KLF6 in the realworld, we conducted a large-scale population cohort study in China comprising 3,375
participants. We used the validated skin aging score SCINEXATM to evaluate skinaging and collected data on genotype, DNA methylation, and lifestyle questionnaire.
We then analyzed 332 SNPs and 368 CpGs located near HES1 and KLF6, or regulating
their expression (eQTL and eQTM), to investigate their association with the skinaging phenotypes. We found 9 SNPs located 10-23kb downstream of HES1 candownregulate HES1 and alleviate solar elastosis, while 5 SNPs can decrease HES1
expression and increase the number of pigment spots on the cheek. Furthermore,
cg10480300 and cg06048750 located on KLF6 are associated with skin aging traits,
including solar elastosis and evenness of pigment spots on the forearm, as well as
lifestyle factors such as BMI and food deficiency. Mediation analysis showed that
cg06048750 mediates the association between BMI, food deficiency, and evennessof pigment spots on the forearm (indirect effect of -0.001 and 0.007 respectively,
both P<0.05), while cg10480300 mediates the association between BMI and solar
elastosis (indirect effect=-0.001, P<0.05). In summary, our findings shed lighton the potential genetic and epigenetic regulatory role of HES1 and KLF6 in the
manifestation of skin aging.

45

Tissue Regeneration and Wound Healing

LB1784Novel scaffold-free 3D skin equivalent to fully replicate human dermal remodelingand epithelialization during wound healing
J. Rorteau1, S. Callejon2, K. Laho1, M. Chaffois1, A. Thepot1, S. Trompezinski,
M. Dos Santos1
1
R&D, LABSKIN CREATIONS, Lyon, France, 2R&D, NAOS ILS, Aix-en-Provence, France|

Late-Breaking ABSTRACTSLB1785

Keratide, a peptide derived from waterfowl feather keratin hydrolysate, activates
TGF-β and JAK/STAT pathways via ERK MAPK signaling to promote skin function
and wound healing
K. Amano1, S. Ohta1, Y. Hosaka2, H. Inoue1
Applied Bioscience, Kanagawa Koka Daigaku, Atsugi, Kanagawa, Japan, 2Keratin
Project, Toyo feather industry co., ltd., Sagamihara, Kanagawa, Japan

1

Abstract Body Restoration of skin after injuries is crucial for life and involves
extensive communication between the different cellular constituents of the diverse
compartments of the skin and its extracellular matrix (ECM). Numerous models ofwound healing have been developed in recent years and are usually restricted toconventional 2D monolayer format. To date, most of the existing 3D bioengineered
wound healing models are mainly based on the use exogenous of non-human scaffold
failing in replicating the modifications of the dermal ECM during the closure process.
Here, we developed a novel 3D bilayered wound healing model consisting of a 3D
dermal equivalent made up entirely of human fibroblasts embedded in their own ECM,
on which epidermal cells were seeded. After 42 days of culture, this scaffold-free 3Dskin equivalent was injured with a biopsy punch, creating a 3 mm wound that extended
through both epidermis and dermis. The wounded region was investigated for up to
12 days in terms of re-epithelialization and dermal remodeling by using histologicaland immunohistological analysis. During the culture period, we observed a complete
re-epithelization and closure of the defect. The epidermis regenerated progressively
from the surrounding wound margins. After 3 days, a migrating tongue of collectively
migrating keratinocytes was detected starting from the differentiated preexistingepithelium across the wound. At day 7, the differentiation of the neoepidermis andthe regeneration of the dermal-epidermal junction were more advanced than toward
the wound center, where the proliferative index was significantly higher. At thedermal level, we observed concomitantly an ECM remodeling with the expression ofcollagens, fibronectin and hyaluronan. Application of healing stimulators significantly
accelerated the healing process suggesting the responsiveness of the model tostimuli. Thus, this novel scaffold-free 3D wound healing model provides a new tool tocapture complex wound healing mechanics as well as to evaluate treatments applied
to wounds.

Abstract Body The skin is the largest organ in the human body and plays a crucial role
as a physical barrier against external agents such as pathogens and chemicals, aswell as in preventing the loss of bodily fluids. The function of the skin is maintainedby the continuous turnover of epidermal keratinocytes that constitute the epidermis,
but this barrier function deteriorates with advancing age. Recent studies havereported that oligopeptides exhibit physiological activity. For example, collagen
tripeptide, derived from collagen, a major protein of the dermis, has been reported
to induce collagen expression and contribute to cartilage regeneration. However, thephysiological effects of peptides derived from keratin, a major protein constituting
the horny tissue, remain unclear. Therefore, in this study, we examined the bioactivityof keratide, peptides derived from waterfowl feather keratin. Immunoblot analysis
showed that keratide increased the expression of epidermal proteins such as
filaggrin in keratinocyte cell line (HaCaT). Additionally, keratide stimulated the
production of collagens in fibroblasts (NHDF). Real-time PCR analysis showed that
keratide increased TGF-β and IL-6 expression by 2.5-fold (p< 0.03) in an ERK MAPK
pathway-dependent manner. The epidermal and dermal proteins whose expression isincreased by keratide were also found to be dependent on the ERK MAPK pathway.
In addition, DNA microarray analysis revealed that keratide promoted the expressionof factors involved in wound healing, such as CXCLs and STAT3, more than 2-fold.
Immunofluorescent staining revealed that keratide induces nuclear translocationof STAT3. Also, scratch assays showed that keratide reduced the gap compared tocontrols in an ERK MAPK pathway-dependent manner. These findings suggest that
keratide enhances skin cell function and activates wound healing by activating the
TGF-β and JAK/STAT pathways via the ERK MAP kinase pathway.

LB1786

LB1787

Transient epigenetic reprogramming by mRNA for skin rejuvenation
C. Monteleon1, S. Menon1, J. Spice1, A. Mohammed1, V. Sebastiano2, 1, E. Hsia1
Turn Bio, Mountain View, California, United States, 2Stanford University, Stanford,
California, United States

1

Abstract Body The purpose of this study was to investigate the potential use oftransient epigenetic reprogramming to rejuvenate aged skin. Primary adult humanfibroblasts or skin explant cultures were dosed transiently with a cocktail of mRNA
encoding transcription factors specifically designed to modify the epigenome andrestore cellular gene expression back to a more youthful state without changing cellular
identity. Subsequently, differential gene expression was analyzed using RNAseq, andprotein expression was evaluated by quantitative immunofluorescence. In fibroblasts,
a strong global transcriptional effect was observed, which amounted to an overallenrichment in extracellular matrix (ECM) protein deposition and downregulation ofcytokine signaling, as concluded by gene ontology analysis. Significant upregulationof genes encoding ECM proteins such as COL1A1 (collagen I), COL3A1 (collagen III),and ELN (elastin), and downregulation of genes encoding ECM degradative enzymes
such as MMP1 and MMP3, was observed. Using immunofluorescence, we found
MMP1 and MMP9 to be decreased by 2-fold (p=0.0278 and p=0.0006, respectively), as
well as the oxidative stress marker, SOD2 (p<0.0001). Furthermore, there was a 2-folddecrease in the senescence marker, p16INK4A (p=0.0022), while expression of the
rejuvenation marker, H3K9me3, was increased by 2-fold (p=0.0021). Cell proliferation
was doubled in treated vs. untreated cells (p<0.0001). In adult human skin explant
cultures, SOD2 was decreased by 2-fold (p<0.05), while collagen VII was increased
3-fold (p=0.0084). Taken together, transient epigenetic reprogramming induces
molecular changes in aged skin at both the cellular and tissue level, which would be
expected to translate into improved skin quality attributes in the clinic. This marks thefirst demonstration of mRNA encoding a cocktail of reprogramming factors having
a global change. Transient epigenetic reprogramming delivered by mRNA could bea novel approach for global skin rejuvenation and age-related disorders of the skin.

Tuning biomaterial stiffness augments innate and adaptive immune responses inthe skin
K. M. Kelly-Scumpia3, L. Shang4, 1, J. S. Weinstein5, D. Di Carlo4, P. O. Scumpia1, 2
1
Medicine/Dermatology, University of California Los Angeles, Los Angeles, California,
United States, 2Dermatology, VA Greater Los Angeles Healthcare System, Los Angeles,
California, United States, 3Medicine/Cardiology, University of California Los Angeles,
Los Angeles, California, United States, 4Bioengineering, University of California
Los Angeles, Los Angeles, California, United States, 5Center of Immunology andInflammation, Rutgers The State University of New Jersey, Newark, New Jersey, UnitedStatesAbstract Body We created microporous annealed particle (MAP) hydrogels as atunable, injectable biomaterial that can form a porous scaffold in injured tissue. We
found that simply by incorporating an antigen into the MAP hydrogel, that we canstimulate hair follicle and sebaceous gland regeneration in healing wounds. In thisstudy, we investigated how the stiffness of the hydrogel affects immune responses
to the hydrogel. We found by tuning the concentration of polyethylene glycol (PEG)
building blocks in the hydrogel, we can change the stiffness of the hydrogel. These
stiffer MAP hydrogels recruited more neutrophils into wounds than MAP hydrogelsof the original stiffness. Using a subcutaneous implant model, we found that stiffer
MAP hydrogels resulted in enhanced recruitment of neutrophils and monocytes
at Day 7 and enhanced recruitment of CD206+ macrophages in wounds at Day
14. Incorporating antigen into stiffer MAP hydrogels resulted in increased highaffinity and low affinity antibody production to the antigen at Day 14 and Day 28.
Interestingly, antibody responses were independent of Toll-like receptor signaling
as MyD88-/-TRIF-/- mice displayed similar immune cell recruitment and antibody
responses to antigen containing MAP scaffolds. Our work offers valuable insights
into how biomaterial cues, including stiffness, represent a novel method to rapidly
tune innate and adaptive immune responses independent of traditional patternrecognition pathways to biomaterials.

46

Tissue Regeneration and Wound Healing

LB1788|Late-Breaking ABSTRACTSLB1789Adipose-derived stem cell exosomes rescue senescence-induced impairment of
migration in epidermal keratinocytes and dermal fibroblasts

The improper down-expression of RNase7 is involved with the hyperproliferation of
keratinocytes and the over-production of collagen in the keloid scar

T. W. Chin1, T. P. Alok2, Z. Poh1, M. Thangaveloo1, C. Fang3, M. Chua3, M. B. Mohd Fadil3,
X. Bi2, N. K. Verma1, D. L. Becker1
1
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore,
Singapore, 2Bioprocessing Technology Institute (BTI), Agency for Science Technology
and Research, Singapore, Singapore, 3Department of Orthopaedic Surgery, Tan Tock
Seng Hospital, Singapore, Singapore

J. Lee, S. Lee, S. Ham, Y. Lee, J. Lee
Dermatology, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (theRepublic of)

Abstract Body Wound healing is a process which occurs in response to skin injury,
in four tightly regulated but overlapping phases: haemostasis, inflammation,
proliferation and remodeling. During the proliferative phase, keratinocytes andfibroblasts migrate into the wound bed to repair and close the wound. However,
the wound healing process can be disrupted by various events such as prolonged
inflammation, impaired proliferation, as well as senescence, leading to the formationof a chronic wound. Using hydrogen peroxide and the NMNPT inhibitor FK866 toinduce senescence in vitro, we show that senescent cells have impaired migratory
capabilities. Furthermore, senescent fibroblasts express elevated levels of the gap
junction protein Connexin 43, which is known to accumulate at the wound edge of
non-healing ulcers. Using chronic wound tissue samples from patients, we show thatwound tissues contain a higher number of senescent cells, with elevated levels of
Cx43. We rescued the senescence-induced impairment of migration using exosomes
derived from adipose derived stem cells. Using mass-spectrometry proteomics andgene ontology enrichment analysis, we show that exosomal proteins are largely
associated with cell adhesion molecule binding functions, and that senescentkeratinocytes express elevated levels of Integrins and Cadherins. We demonstrate
the potential of exosomes as a wound healing therapeutic by using an in-house modelof perturbed wound healing in Sprague Dawley rats. Our results show that senescentcells have impaired migratory capabilities with elevated levels of gap junction andadhesion proteins. The impairment of migration is attenuated by exosomes, anddemonstrate the potential of exosomes as a wound healing therapeutic.

LB1790RNAi-based topical formulation to treat chronic diabetic foot ulcers
P. Sampath1, 2, G. Subramanian1, K. Kalidasan1, J. Chan1, S. Quah1
1
A*STAR Skin Research Labs (A*SRL), Agency for Science Technology and Research(A*STAR), Singapore, Singapore, 2Genome Institute of Singapore, A*STAR, 60 Biopolis
Street, Genome, Singapore, Singapore

Abstract Body Diabetic foot ulcers (DFUs) are devastating complications of diabetes;
one in four diabetics will develop a non-healing chronic foot ulcer, which potentiallyleads to lower limb amputation. This globally escalating medical issue lacks approved
pharmacologic options. In the absence of such solution, we discovered persistentand aberrant expression of an anti-migratory small non-coding microRNA, miR-198,in the microenvironment of chronic wounds, which prevents keratinocyte migration,
re-epithelialization, and wound healing (Sundaram et.al, Nature 2013). Moreover, noncell-autonomously miR-198 inhibits endothelial cell recruitment and angiogenesis.
Overall, the pleiotropic nature of miRNA-198, and the ability of this tiny molecularrheostat to regulate the expression of an entire cohort of functionally related genes,
makes this an attractive drug target for chronic wounds. With the deployment of an
integrated RNAi therapeutics approach, coupled with a judicious combination ofchemical modifications to enhance cellular uptake, target specificity, and metabolicstability, we designed sequence-specific antagomiR oligonucleotides (AMOs-198) toeffectively target miR-198. Cell-penetrating-peptides (CPP), which form non-covalent
complexes with AMOs-198, facilitate effective delivery of these oligomers. With thedepletion of anti-migratory miR-198, we observed the restoration of all pro-migratory
targets of miR-198, which promote effective migration of keratinocytes towards
the wound edge, leading to wound closure. The efficacy of these highly specificand non-toxic AMOs-198/CPP complex was validated by in-vitro and 3D-ex-vivo deepidermized dermis (DED) and human organ culture model systems. We envisage
the development of the first-of-its kind, early intervention therapeutic to acceleratehealing of DFUs, mitigate complications and prevent lower extremity amputations.

Abstract Body Keloids are raised hard scars that form from excessive collagendeposition and a combination of interconnected scar tissues. This is most oftencaused by genetic factors or the incorrect regulation of factors that induce collagenproduction. RNase7 is an anti-microbial peptide, its expressions have been linked toskin health, inflammation, and cell death. We found the improper down-expressionof RNase7 in the keloid than normal skin via RNA-Seq analysis. In the keloid-derived
keratinocytes, the migration actively occurs more than in the normal keratinocyte.
To evaluate the mRNA expression levels, qRT-PCR was performed, and the results
showed the over expressions of MMP2 and MMP9 genes in the keloid tissue sample
and the keloid-derived keratinocyte. In addition, the mRNA expressions of TIMP1
and TIMP2 genes, regarding the regulation of MMP2 and MMP9, were reduced.
The results of immunohistological staining showed the over-expression of MMP2
and MMP9 in the keloid. Taken together, this study investigated the relationshipbetween RNase7 and keloid. The down-expression of RNase7 has led to an increasein the expression of MMPs that are downstream of RNase7, which suggests thedownregulation of RNase7 is closely associated with the dysregulation of their
proliferation and differentiation. Therefore, it is thought that a decrease in the activityof RNase7 plays a key role in the formation of keloids.

LB1791

Oleogel-S10 (birch bark extract) in dystrophic epidermolysis bullosa: A case series
evaluating the impact on wound burden over 2 years
M. Torres-Pradilla1, 4, E. Álvarez2, 5, M. Novoa1, 4, I. Lozano3, M. Trujillo3
1
Fundacion Universitaria de Ciencias de la Salud, Bogota, Cundinamarca, Colombia,
2
Universidad de Cartagena, Cartagena, Colombia, 3Fundación Hospital Pediátrico dela Misericordia, Bogotá, Colombia, 4Hospital Infantil de San José, Bogotá, Colombia,
5
Hospital Infantil Napoleón Franco Pareja, Cartagena, Colombia

Abstract Body Epidermolysis bullosa (EB) is a devastating group of rare, inherited
diseases affecting epithelial integrity that results in tears, sores, blisters anddebilitating wounds. Impaired wound healing is central and can lead to serious
clinical complications, deformities, and symptoms with a devastating impact on
QoL. The Phase 3 EASE study previously demonstrated that Oleogel-S10 accelerated
wound healing and reduced wound burden in EB. This is the first report to evaluate
the effectiveness of Oleogel-S10 in clinical practice. Patients with dystrophic EB
were treated with Oleogel-S10 as part of an early access program across 3 sites inColombia. A retrospective analysis of medical records was conducted for up to 24
months. Effectiveness was assessed by measuring body surface area percentage(BSAP) and tolerability was monitored throughout. Data from 13 patients wereanalyzed; 69.2% were female and the median age was 19 years (range; 3 to 53). All
patients had generalized dystrophic EB with a mean BSAP pre-treatment of 27.3%(range; 11% to 47%). At 6, 12, 18 and 24 months post Oleogel-S10 treatment, mean
BSAP reduced to 19.6%, 13.2%, 10.17%, and 10.4%, respectively. No safety signals
related to treatment were observed. During follow-up, 2 patients with worsening
wounds related to the use of conventional dressings were recorded. Two deaths
were reported during treatment interruption due to severe anemia, cardiopulmonary
complications and possible infection. These data demonstrate, for the first time, theeffectiveness of Oleogel-S10 in a real-life setting with clinical meaningful reductionsin BSAP over 24 months. This is particularly encouraging given the chronic nature ofthis disease as well as the challenging setting where treatment interruptions related
to access barriers can be common.

47

Tissue Regeneration and Wound Healing

LB1792|Late-Breaking ABSTRACTSLB1793

CCL2 restores adult cells to regenerate hair follicles by microenvironmental
regulation

Hibiscus-derived peptide, Tyr-Pro (YP) promotes human keratinocyte migration by
activating FAK/ERK/MAPK signaling pathway

W. Wu1, 2, W. Zhou3, J. Jiang1, M. Wang1, J. Zhang1, X. Shen1, Q. Tang2, H. Liu2, L. Yang1,
M. Lei1
1
Bioengineering, Chongqing University, Chongqing, China, 2Chongqing University Three
Gorges Hospital, Chongqing, China, 3Chongqing University Cancer Hospital, Chongqing,
China

D. Seo1, Y. Jang1, H. Kim1, S. Lee3, S. Moh3, S. Choi5, L. Germain4, D. Kim2, J. Shin2
1
Biology, CHA University School of Medicine, Seongnam, Gyeonggi-do, Korea (theRepublic of), 2Dermatology, CHA Bundang Medical Center, Seongnam, Gyeonggi-do,
Korea (the Republic of), 3Plant Cell Research Institute, BIO-FD&C Co., Ltd, Seongnam,
Gyeonggi-do, Korea (the Republic of), 4Department of Surgery, Faculty of Medicine,
Université Laval, CHU de Québec-Université Laval Research Centre, QC G1J1Z4,
Quebec, Canada, 5Daesang Holidings Co,. Ltd, Seoul, Korea (the Republic of)

Abstract Body Aged cells have a reduced ability to regenerate tissues. Thus, it is
intriguing to reactivate the adult cells to regenerate. Here, we used hair follicles as amodel to study how mechanical stimuli induce hair regeneration using hair plucking
and organoid culture approaches in adult mice. We observed that skin organoidcultures using cells derived from day 3 post-plucking (PPD3) skin had the highest
hair regeneration capacity. The regenerated hair follicles had normal morphology.
By RNA-sequencing, single-cell RNA-sequencing analysis, and in situ hybridization,
we identified that the chemokine signaling pathway genes including Ccl2 aresignificantly increased in the hair follicle and surrounding dermal microenvironment
at PPD3, as well as in skin organoid cultures. Immunostaining shows that the PPD3
skin epithelial cells have increased multipotency. Under organoid culture, these skincells can self-organize to form epidermal aggregates. By adding CCL2 recombinant
protein to the skin organoid culture using an environmental reprogramming protocol,
we observed the adult cells which lose their regenerative ability can self-organize inorganoid culture and regenerate hair follicles upon transplantation. In summary, we
elucidate the mechanism by which mechanical stimulus induces hair regeneration at
the microenvironmental regulation level using the hair plucking and organoid culture
models. Our study reinforces the concept of immune regulation in hair regeneration
under mechanical stimuli. The immune modulation in the skin organoid culture
system also provides therapeutic potential for future clinical application.

Abstract Body Background: Wound healing is a process of that repairs damaged
or lost tissue, and the migration of epithelial cells is essential for restoring the skinbarrier function. Although Hibiscus sabdariffa extract has been reported to enhancewound healing process, the exact mechanism has not been elucidated yet. Objective:
In this paper, we evaluated the effect of tyrosine-proline (YP), a dipeptide identified
from Hibiscus sabdariffa plant cells, on keratinocyte migration. Method: YP, one ofthe dipeptide derived from Hibiscus sabdariffa plant cells, was synthesized using thesolid phase peptide synthesis method. Normal human keratinocytes were treatedwith YP for 24 hours. Wound migration assay, RT-qPCR assay, and Western blot
analysis were performed to analyze the effect of YP on keratinocyte migration and to
elucidate its signaling pathway. Result: Treatment with YP induced effective migration
in a wound migration assay. Western blot analysis showed that the phosphorylationof FAK and ERK was increased with YP treatment. Additionally, the expression ofepithelial-mesenchymal transition-related transcription factors, ZEB1 and TWIST1,
was up-regulated in YP-treated keratinocytes. Moreover, treatment with YP downregulated the expression of differentiation-related genes, such as CLDN1, TJP1, andDSG1, and basement membrane integrity-related genes, COL17A, ITGA6, and ITGB4.
Conclusion: Collectively, our study demonstrates that Hibiscus sabdariffa plant cellderived peptide YP induces effective keratinocyte migration through the activationof FAK/ERK/MAPK signaling and up-regulation of EMT-related transcription factors.
These findings suggest that YP may have therapeutic potential for promoting woundhealing.

LB1794

LB1795

I. Fatima1, A. Mardaryev2, E. Rozhkova1, A. Seluanov3, V. Gorbunova3, A. Veves4,
A. Sharov1, V. A. Botchkarev1
1
Dermatology, Boston University School of Medicine, Boston, Massachusetts, UnitedStates, 2Centre of Skin Sciences, University of Bradford, Bradford, West Yorkshire,
United Kingdom, 3Biology, University of Rochester, Rochester, New York, United States,
4
Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

M. Kida1, I. Fatima1, E. Rozhkova1, M. Wu1, M. Otero-Viñas2, P. Cole3, V. Falanga1,
R. Alani1, A. Sharov1
1
Dermatology, Boston University School of Medicine, Boston, Massachusetts, UnitedStates, 2University of Vic – Central University of Catalonia, Vic, Spain, 3Harvard
University, Cambridge, Massachusetts, United States

Mechanisms regulating scar-free wound healing in long-lived naked mole-rats

Abstract Body Naked mole-rats (NMRs, Heterocephalus glaber) are unique longlived mammals that possess marked resistance to cancer and other age-related
pathologies maintaining a sustained healthy life-span for over 30 years. To study
mechanisms regulating skin regeneration after injury, full-thickness wounds werecreated in the back skin of NMRs. In contrast to mice, wound closure in NMR skin wasachieved primarily by re-epithelialization/granulation tissue formation and exhibited
relatively minimal (~26%) wound contraction. Three months after wounding, the fully
re-epithelized wounds lacked pigmentation, while dermis showed a clear reductionof scarring. RNAseq analyses performed on the full-thickness wounds revealed thatthree weeks after skin injury (i.e. a time-point corresponding to the beginning of scarformation in human skin), the major differences between wounded and unwoundedskin included changes in expression of extracellular matrix-associated genes, genes
involved in collagen fibril organization, Wnt and Toll-like receptor signaling pathways,
and epigenetic regulators (Cbx4, Satb1). Single cell RNA sequencing revealed uniquetranscriptome profile in the fibroblast subpopulation expressing fibrotic markers
and showing upregulation of the Col3a1 gene. Immunofluorescent validation of theRNAseq data revealed high expression levels of Col3a1 as a marker of immaturecollagen fibers in the dermis. Transcriptional profiling of TGFβ isoforms and different
pro/anti-inflammatory cytokines revealed a balance in the expression of different
cytokines, potentially contributing to reduced scarring in NMRs. These data provide
novel insights into mechanisms regulating scar formation after skin injury, andenhance the innovative potential of securely establishing a place for the NMR as amodel organism for studying the biology and regeneration of human skin.

Dual LSD1/HDAC inhibition accelerates skin wound healing

Abstract Body The epigenetic machinery regulates epidermal homeostasis andkeratinocyte differentiation is normal skin, while epigenetic control of the woundhealing remain relatively underexplored. The HDAC1/2 and LSD1 enzymatic activities
within the CoREST complex are commonly associated with silencing of gene
expression. Corin is a synthetic hybrid agent derived from the HDAC inhibitor (MS275) and LSD1 inhibitor. In this study, using in vivo mouse tail wound healing model,
we found that HDAC1 and LSD1 expression levels in epidermal keratinocytes show
dynamic changes after injury compared to uninjured skin. Corin treatment resulted inaccelerated wound closure in dose-dependent manner. Histological analysis revealed
that 100nM corin significantly promoted regeneration of the epithelium 10 days after
wounding. In epidermal keratinocytes treated with corin, the expression of H3K9Ac
was increased compared to controls, while the expression of H3K4Me2 was notchanged. In addition, corin treatment significantly stimulated migration of humankeratinocytes in vitro, while their proliferation was reduced. qRT-PCR gene expression
analysis of corin-treated keratinocytes showed significant upregulation of the genes
associated with cell migration, such as CD24, EPHB2, ITGAX, PTGS, SCT1, SERPINB2,SERPINE1, and SLPI. In summary, our study demonstrates that dual HDAC1 andLSD1 inhibition by corin promotes acetylation of H3K9 and skin wound healing via
stimulation of migratory activities of epidermal keratinocytes.

48

Translational Studies|

Late-Breaking ABSTRACTSLB1796

LB1797

C. Chamayou-Robert1, M. Pujos1, L. Ma2, O. Doucet1
Discovery & Innovation R&D, COTY, Monaco, Monaco, 2Discovery & Innovation R&D,
COTY, Shanghai, China

N. Jariwala1, M. Ozols1, 2, 3, A. Eckersley1, R. E. Watson1, 4, B. Mambwe1, A. Gilmore1,
L. Debelle1, 5, M. Bell6, E. J. Bradley6, Y. Doush6, R. Leroux7, O. Peschard7, P. Mondon7, C.
Ringenbach7, L. Bernard7, A. Pitois7, M. J. Sherratt1
1
The University of Manchester, Manchester, United Kingdom, 2Wellcome Sanger
Institute, Hinxton, United Kingdom, 3British Heart Foundation Centre of Research
Excellence, Cambridge, United Kingdom, 4Agency for Science Technology andResearch, Singapore, Singapore, 5Universite de Riems Champagne Ardenne, Riems,
France, 6No7 Beauty Company Nottingham, Nottingham, Greater Nottingham, United
Kingdom, 7Sederma, Le Perray-en-Yvelines, France

8-oxoguanine glycosylase contributes to restore DNA integrity of epidermal &dermal cells exposed to stress hormones released during psychological stress

1

Abstract Body Cell DNA is continuously impacted by endogenous factors inducedby cell metabolism and by psychological stress. Both may contribute to generate
reactive oxygen species leading to DNA damage affecting cell replicative function andpromoting skin premature ageing. The objective of the study was to assess whether
a liposome-vectorized DNA repair enzyme containing 8-oxoguanine glycosylase
could reverse some DNA damage induced by psychological stress. For that purpose,skin cells, normal human keratinocytes and fibroblasts were incubated with cortisoland epinephrine, two main mediators released under psychological stress. Normal
human keratinocytes and normal human fibroblasts were exposed to increasing
doses of either cortisol or epinephrine. Following the stress, cells were immediately
treated with liposome-vectorized glycosylase enzymes. DNA damage was quantified
by using single cell gel electrophoresis assay. Cortisol exposure induced a significant
increase of oxidative lesions, such as 8-oxoguanine in normal human keratinocytes
and fibroblasts. This DNA damage was clearly reduced by liposome-vectorized
glycosylase enzyme treatment in both cell types. Exposure to epinephrine also
increased oxidative lesions. Similarly, glycosylase enzyme treatment accelerated DNA
repair compared to non treated skin cells. Under psychological stress, endogenous
messengers, such as cortisol and epinephrine, are released and can reach skin cells
generating oxidative damage in both keratinocytes and fibroblasts DNA. Under theexperimental conditions used, we demonstrated that liposomes-encapsulated 8-oxoglycosylase enzymes very significantly reduced oxidative lesions by promoting baseexcision repair (BER) pathway.

LB1798Novel tetra-peptide matrikines mediate dermal and epidermal metabolism in humanskin

Abstract Body Aberrant and progressive remodeling of the dermal extracellularmatrix (ECM) as a result of intrinsic and extrinsic ageing can profoundly affectclinical skin appearance and function. Exogenous, topically applied, ECM-derived
peptides (matrikines), have been used to modulate skin biology, enhancing synthesisof specific ECM proteins and reducing some clinical signs of extrinsic skin ageing.
Here, for the first time, we have applied machine learning approaches proteomewide to predict two novel peptides (GPKG and LSVD; potential cleavage products ofcollagen I and fibulin-1 respectively) and to assess their effects on the transcriptome
and proteome of cultured human dermal fibroblasts and on the transcriptome ofskin biopsies taken from volunteers. In combination, these peptides acted in vitro
to significantly enhance the transcription of genes implicated in ECM organization,
cell proliferation and lipid metabolism. In skin, the peptides enhanced the cutaneous
expression of genes involved in antioxidant activity, skin barrier formation, anddermal ECM organization. This study demonstrates that in silico prediction of peptide
cleavage sites can identify novel, biologically active peptides which affect multiple
cellular tissue processes associated with maintenance of healthy skin function, andthe repair of aged and photoaged skin.

LB1799Tolerance induction in a preclinical pemphigus vulgaris (PV) mouse model utilizing
desmoglein 3 peptides-conjugated nanoparticles

Single-cell type proteomic analysis in FFPE tissue sections of severe cutaneousadverse drug reactions

C. Hudemann1, D. Krzikalla2, B. Metzler2, R. Digigow2, R. Eming3, M. Hertl1, S. Fleischer2,
H. Garn4
1
Department of Dermatology and Allergology, Philipps-Universitat Marburg, Marburg,
Hessen, Germany, 2Topas Therapeutics GmbH, Hamburg, Germany, 3Departmentof Dermatology and Venereology, German Armed Forces Central Hospital Koblenz,
Koblenz, Germany, 4Translational Inflammation Research Division, Philipps-University
Marburg, Marburg, Germany

T. Nordmann1, H. Anderton2, S. Lisa1, S. Ankit1, P. C. Stadler3, J. Silke2, L. E. French3,
M. Mann1
1
Proteomics and Signal Transduction, Max Planck Institute for Biochemistry,
Martinsried, Germany, 2Cell Signalling and Cell Death division, Walter and Eliza
Hall Institute of Medical Research, Melbourne, Victoria, Australia, 3Department of
Dermatology and Allergology, Ludwig-Maximilians-Universitat Munchen, Munchen,
Bayern, Germany

Abstract Body PV is a severe autoimmune disorder of mucous membranes and skincaused by IgG autoantibodies against desmoglein (Dsg) 3 and Dsg1. Pathogenesis
depends on recognition of Dsg3 epitopes by autoreactive T cells, often restricted by
HLA-DRB1*04:02. Aiming at inducing antigen-specific immune tolerance, peptides
representing HLA-DRB1*04:02 restricted T cell epitopes were coupled to nanosized
Topas particles (TPCs). We demonstrated the potency of TPCs in vitro to induce
proliferation and cytokine release of T cells of mice transgenic for human HLADRB1*04:02/CD4 interaction, previously immunized with human Dsg3. To assess thein vivo efficacy of the Dsg3 epitope-loaded TPCs, transgenic mice were immunized
twice at days d0 and d14 with human Dsg3 and treated intravenously with a mix of
TPCs one day prior to each immunization. At d28 we could demonstrate a significant
and concentration-dependent reduction of Dsg3-specifig IgG titers in animals treatedwith TPCs in comparison to controls. We further analyzed underlying immunologicalmechanisms by single immunization and TPC treatment at d0 and d-1, respectively.
At d7, we found that TPC application compared to empty particle control induced an
upregulation of FoxP3+ regulatory T cells primarily in the spleen. Our data suggestthat the applied TPC-mediated tolerance induction protocol leads in Dsg3-immunized
HLA transgenic mice to an early increase in potentially protective Treg cells, whichmight have an impact on B cell functions resulting in a reduction of anti-Dsg3 IgG
antibody titers. This promising approach underlines the potential effects of peptideloaded TPCs to restore immunological tolerance in PV via modulation of autoreactive
T cells.

Abstract Body Driven by inflammation, cutaneous adverse drug reactions range
from being benign and self-resolving to rare and life-threatening. The cellular andmolecular mechanisms underlying drug-induced activation of cutaneous immunity
remain largely unexplored. To unravel the molecular mechanisms leading to severe
cutaneous adverse drug reactions, we apply unbiased, mass spectrometry-based
proteomic analysis of single-cell types with preserved spatial resolution from routine
FFPE tissue sections using Deep Visual Proteomics, a recently developed methodby our laboratory (Nature Biotechnology, 2022). For this, AI-based image analysis
was performed to identify and correctly segment CD45+ immune cells and CK+
keratinocytes in skin biopsies from patients suffering from TEN, DRESS and MPR aswell healthy controls, followed by precise single-cell laser microdissection. Using thisworkflow in combination with high-sensitivity mass-spectrometry, we quantify over
4500 unique proteins in keratinocytes (CK+) and immune-cells (CD45+) across allcohorts. Interestingly, principle component analysis of keratinocytes and immunecells reveals cell-type unique and distinct clustering, indicating the existence ofdiverse and cell-type specific mechanisms within the same disease. Furthermore,
Gene Set Enrichment Analysis identifies a common mechanism of increased cytokine
signaling, paving the way for new treatment strategies. In summary, Deep VisualProteomics has the potential to provide novel and translational insights into clinicallyrelevant, dermatological disease mechanisms for improved patient care.

49

Translational Studies |LB1800

TWEAK-induced apoptosis depletes desmoglein 1 and 3 via STAT1 in pemphigus
Y. Liu, X. Peng, Y. Xia
Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China

Abstract Body Purpose of the study: To investigate the role of TWEAK in manipulating
keratinocyte apoptosis and its subsequent effects on the expression of Dsg1 andDsg3 in the pathogenesis of pemphigus. Abstract: Pemphigus is a life-threatening
autoimmune skin disease characterized by a loss of epidermal keratinocyte adhesion
associated with depletion of desmoglein (Dsg) 1 and 3. Previously, we elucidated
that tumor necrosis factor-like weak inducer of apoptosis (TWEAK) weakened
cell adhesion via binding to fibroblast growth factor-inducible 14 (Fn14). Here, we
further investigated the role of TWEAK in manipulating the expression of Dsg1 andDsg3 in pemphigus. In the lesional and perilesional skin of pemphigus patients,
overexpression of TWEAK (p=0.0181) and significant apoptosis (p<0.0001) were
found concurrently. However, the expression of Dsg1 and Dsg3 decreased, which
led us to speculate that TWEAK may promote keratinocyte apoptosis to deplete
Dsg1 and Dsg3, therefore, participating in the pathogenesis of pemphigus. In vitro
experiments showed that TWEAK-stimulated keratinocytes had increased apoptosis
and decreased Dsg1 (p=0.0063) and Dsg3 (p=0.0368) expression, while Fn14 RNA
interference reversed the effects, validating our speculation. Bulk-RNA sequencing
and western blotting revealed that it was caspase-3 mediated the apoptosis andDsg1/3 depletion after TWEAK stimuli, while the administration of caspase inhibitors
Z-VAD and Boc-D further validated it. TWEAK-stimulated keratinocytes also exhibited
STAT1 activation, which has been proven to promote TWEAK-induced apoptosis. In
addition, apoptosis and Dsg1/3 reduction were efficiently blocked by STAT1 inhibitor
Fludarabine. These data indicate that TWEAK may play an anti-adhesion role via
apoptosis-induced Dsg1/3 depletion regulated by STAT1 phosphorylation. Thus,
TWEAK may serve as a biomarker or therapeutic target for pemphigus.

Late-Breaking ABSTRACTSLB1801A multi-omic single-cell atlas of Stevens-Johnson syndrome and toxic epidermal
necrolysis
A. Gibson2, Y. Li2, R. Gangula1, A. Chopra2, E. Mukherjee1, A. Palubinsky1, C. Campbell1,
J. Peter3, R. Lehloenya3, J. Trubiano4, P. Choshi3, M. Porter3, S. Mallal1, 2, R. Ram2,
E. J. Phillips1, 2
1Vanderbilt University Medical Center, Nashville, Tennessee, United States, 2Murdoch
University, Murdoch, Western Australia, Australia, 3Dermatology, University of CapeTown, Rondebosch, Western Cape, South Africa, 4Infectious Diseases, University of
Melbourne Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia

Abstract Body We aimed to construct a multi-omic single-cell atlas of StevensJohnson syndrome and toxic epidermal necrolysis (SJS/TEN) by examining gene,protein and T-cell receptor (TCR) expression in blister fluid and skin. We performed
5’ scRNA-TCR-cellular indexing of transcriptome and epitopes (CITE)-sequencing on
unaffected and affected skin and/or blister fluid from SJS/TEN patients. Following
single-cell sequencing, we performed bioinformatic normalization (CellRanger
v6.1.2), transcriptome-based clustering (Seurat v4.1.1), and visual and statisticalanalyses (scCODA, VGAS). The single-cell atlas includes 176,524 cells, which span
18 scRNA-defined immune- and tissue-relevant subtypes, confirmed by scCITEseq. CD8+ T-cells were significantly enriched in SJS/TEN blister fluid (scCODA
p<0.05). Differential gene expression analyses identified shared signatures of cells
in SJS-affected skin and blister fluid. Monocytes/macrophages shared an M1-likeinflammatory signature (STAT1, HLA, CXCL10), and CD8+ T-cells a signature alignedwith cytotoxicity (GNLY, GZMB), interferon-induced signaling (IFITM1, STAT1), andproteasomal processing (PSMB9, PBMB10). Integrated scTCR-seq identified thesame expanded clonotypes in both affected skin and blister fluid; expressed on thesame T-cell sub-populations absent from or unexpanded in unaffected skin. ThisSJS/TEN single-cell atlas acts as an unbiased multi-omic tool for patients clusteredby drug and reaction which can be used to define specific tissue-relevant signaturesof pathogenic antigen-driven oligoclonal T-cells at the site of tissue damage relevant
to development biological markers for diagnosis, prognosis and treatment

50

ISID 2023 Meeting – Late-Breaking AUTHOR INDEXÁÁlvarez, Erick - LB1791

A

Abbasi, Ali - LB1720
Abe, Riichiro - LB1717
Abe, Risa - LB1716
Abuabara, Katrina - LB1687, LB1714
Adam, Eva - LB1721
Adams, Jackson - LB1751
Admane, Chloë - LB1781
Adotévi, Olivier - LB1657
Ahmad, Wajdie - LB1752, LB1753
Ahmed, Hanof - LB1667
Ahuja, Sonya - LB1710
Aioi, Akihiro - LB1711
Akgul, Baki - LB1661
aki, ryoichi - LB1778
Aladwan, Safwan M. - LB1699
Alam, Rian - LB1691
Alani, Rhoda - LB1795
Ali, Iman - LB1664
AlMarsomy, Sarah - LB1721
Almet, Axel - LB1674
Alok, Tanala P. - LB1788
Alomari, Muhannad - LB1739
Amano, Koyo - LB1785
Amato, Antonino - LB1750
Ameri, MohammadMilad - LB1643
Amirthalingam, Muthukumar - LB1745
Amoh, Yasuyuki - LB1778
An, Susun - LB1759
Andersen, Bogi - LB1671, LB1674
Anderton, Holly - LB1799
Andor, Noemi - LB1658
Anene, Chinedu - LB1663
Angsana, Julianty - LB1641
Ankit, Sinha - LB1799
Annusver, Karl - LB1674
Antiga, Emiliano - LB1634
Antonevich, Sarah - LB1706
Aoki, Valeria - LB1687
Arakawa, Nobuko - LB1778
Arbel, Yifat - LB1768, LB1769
Arbel, Yuval - LB1768, LB1769
Ardeshirdavani, Armin - LB1660
Arney, James - LB1739
Arun, Banu - LB1683
Asad, Samina - LB1728
Assan, Florence - LB1726
Athar, Mohammad - LB1763
Aubin, François - LB1657
Avdieiev, Stanislav - LB1658
Awethe, Zaynah - LB1684
Ayers, Jessica L. - LB1722

B

Bahamondes Lorca, Veronica - LB1756
Bailey, Emma - LB1663
Bang, Chul Hwan - LB1757, LB1760
Barbieri, John - LB1682
Barbosa, Silvia - LB1777
Bartlett, Edmund K. - LB1707
Basgaran, Amedra - LB1739
Bauer, Johann - LB1634, LB1725
Beak, Sunghee - LB1668, LB1669
Bechara, Falk - LB1776
Becker, David L. - LB1788
Befekadu, Annisa - LB1728
Bell, Mike - LB1797
Bence, Gálik - LB1721
Bennett, Brydon - LB1750
Bernard, Laure - LB1797
Bertolini, Marta - LB1641, LB1776, LB1777
Bertschi, Nicole - LB1645
Beutner, Karl - LB1765
Bewicke-Copley, Findlay - LB1663
Bhat, Laxminarayan - LB1745

Bhat, Seema R. - LB1745
Bhatia, Shailender - LB1681
Bhogal, Ranjit K. - LB1780
Bi, Xuezhi - LB1788
Bickers, David R. - LB1763
Bierma, Marika - LB1681
Bierman, John - LB1762
Bigliardi, Elena - LB1758
Bigliardi, Paul - LB1758
Bigliardi Qi, Mei - LB1758
Bilcha, Kassahun - LB1728
Billi, Allison - LB1671
Bilousova, Ganna - LB1719, LB1727, LB1730
Bíró, Tamás - LB1776
Blauvelt, Andrew - LB1703
Bordeaux, Jeremy S. - LB1764
Bordeaux, Zachary A. - LB1751
Botchkarev, Vladimir A. - LB1794
Boullerot, Laura - LB1657
Bradley, Eleanor J. - LB1797
Bradley, Maria - LB1728
Braiman, Liora - LB1754
Brener, Ephraim - LB1754
Brodesser, Susanne - LB1715
Brooks, Tony - LB1723
Brown, Joel - LB1658
Brown, Sara - LB1687, LB1731
Bruckner, Anna - LB1730
Brüggen, Marie-Charlotte - LB1643, LB1685
Buckman, Cody - LB1747
Burmester, Imke - LB1644
Busch, Hauke - LB1644
Byrd, Nnaemeka - LB1706

C

Caley, Matthew - LB1754
Callejon, Sylvie – LB1784
Callens, Tom - LB1656
Campbell, Chelsea - LB1801
Campbell, Taaliah - LB1747
Cangkrama, Michael - LB1654
Cao, Qiaoyu - LB1729
Cao, Shensong - LB1742
Castillo Flores, Jocelyn - LB1730
Caviola, Elisa - LB1755
Celli, Anna - LB1714
Cevikbas, Ferda - LB1751, LB1777
Chaffois, Marie-Océane - LB1784
Chamayou-Robert, Cecile - LB1796
Chambers, John - LB1740
Chan, Justin - LB1790
Chaolan, Pan - LB1729
Chaskar, Prasad D. - LB1670
Chavez Chiang, Omar - LB1658
Chekanov, Konstantin - LB1652
Chen, Chun-Bing - LB1746
Chen, Dana - LB1763
Chen, Huizhen - LB1742
Chen, San-Chi - LB1746
Chen, Suephy - LB1708
Chen, Y Ann - LB1658
Chen, Yu - LB1742
Chen, Zhihua - LB1658
Cheng, Hui-Ching - LB1779
Cheng, Quan - LB1638
Cheng, Tsing - LB1720
Cheng, Yuan-Bin - LB1744
Chiang, Pinhsuan - LB1746
Chin, Toby W. - LB1788
Cho, Hoon - LB1757, LB1760
Cho, Jaewon - LB1759
Cho, Kathleen - LB1665
Cho, Soo Ick - LB1649
Cho, Sun-A - LB1759
Choi, Haeyoun - LB1757
Choi, Jung min - LB1675
Choi, Sunbeen - LB1668, LB1669
Choi, Sung Soo - LB1676, LB1793
Choi, Yonghee - LB1732
Chopra, Abha - LB1801

Choshi, Phuti - LB1801
Chua, Min Jia - LB1788
Chuong, Cheng-Ming - LB1774
Church, Candice - LB1681
Clemens, Clara - LB1685
Cohen, Jeffrey M. - LB1682
Cole, Philip - LB1795
Common, John E. - LB1740
Connor, Jason - LB1698
Cornman, Hannah - LB1751
Corredor, Jessica - LB1683
Craig, Paul - LB1663
Crow, Yanick - LB1726
Cunha, Tomas - LB1636

D

D'Amato, Alfonsina - LB1755
Dang, Ningning - LB1734
Danis, Judit - LB1721
Danko, Daniil I. - LB1652
Davey, Robert A. - LB1743
Daza, Nicolas - LB1706
Debelle, Laurent - LB1797
del Agua, Nathalie T. - LB1779
Delanoue, David - LB1739
Dhar, Sandipan - LB1687
Di, We-Li - LB1723
Diamond, Carrie - LB1708
Di Carlo, Dino - LB1787
Didona, Dario - LB1636, LB1640
Diette, Nicole - LB1727
Digigow, Reinaldo - LB1798
Ding, Xiaolei - LB1715
Dlugosz, Andrzej - LB1665
Dons, Frederikke E. - LB1712
Dos Santos, Morgan - LB1784
Doucet, Olivier - LB1796
Doush, Yegor - LB1797
Duan, Cheng - LB1741
Dummer, Reinhard - LB1643

E

Eckersley, Alexander - LB1797
Edelkamp, Janin - LB1776, LB1777
Edwards, Roger - LB1697
Ehst, Benjamin - LB1703
Eichenfield, Lawrence F. - LB1687
Eisfeldt, Jesper - LB1728
Elias, Ellen - LB1727
Elias, Martina - LB1731
Elias, Peter M. - LB1714
Eliovits, Nick - LB1765
Elliott, Paul - LB1740
Elmais, Mariam - LB1763
Elmaraghy, Hany - LB1702
Elmets, Craig A. - LB1656
Elmgren, Julia - LB1728
Eming, Rüdiger - LB1798
Eming, Sabine - LB1715
Erickson, Kayley L. - LB1764
Escamilla, Jazmin - LB1727
Etorban, Mona - LB1731
Evans, Megan - LB1688
Eyerich, Kilian - LB1641

F

Fábos, Beáta - LB1721
Fairley, Janet A. - LB1646
Falanga, Vincent - LB1795
Fan, Xinyi - LB1691
Fan, Xiying - LB1735
Fang, Christopher - LB1788
Fang, Yongxing - LB1685
Fatima, Iqra - LB1794, LB1795
Fazal, Maria - LB1689
Fehrholz, Markus - LB1776
Feng, Hao - LB1638
Ferland, Karel - LB1767

51

ISID 2023 Meeting – Late-Breaking AUTHOR INDEX
Ferris, Laura - LB1709
Fitzsimmons, Robert - LB1694
Fleck, Anthony M. - LB1743
Fleischer, Sabine - LB1636, LB1798
Flohr, Carsten - LB1687
Flora, Akshay - LB1700
Flores, Elsa - LB1658
Flores, Idayri - LB1695
Forman, Seth - LB1702
Foster, April R. - LB1781
Foster, Barbara A. - LB1662
Franz, Sandra - LB1775
Fremond, Marie-Louise - LB1726
French, Lars E. - LB1799
Frew, John W. - LB1700
Fritz, Björn - LB1677
Fu, Alex - LB1681
Fu, Siying - LB1651
Fu, Xinyi - LB1651, LB1653
Fu, Yueying - LB1701
Fujisawa, Yasuhiro - LB1632
Fujita, Mirei - LB1673
Funakoshi, Ayaka - LB1771
Funk, Tracy - LB1698

G

Gaebelein, Christoph - LB1654
Gambardella, Laure - LB1781
Gangula, Rama - LB1801
Garate, David - LB1695
Garcia, Gustavo - LB1666
Garn, Holger - LB1798
Gatenby, Robert - LB1658
Gay-Mimbrera, Jesus - LB1733
Gellen, Emese - LB1662
Georgievskaya, Anastasia - LB1652
Germain, Lucie - LB1676, LB1767, LB1793
Getachew, Ethiopia - LB1770
Ghersin, Hila - LB1678
Gibson, Andrew - LB1801
Giesler, Sophie - LB1660
Gil, Esther Garcia - LB1702
Gilhar, Amos - LB1753
Gilmore, Andrew - LB1797
Giordano, Sharon - LB1683
Goff, Peter H. - LB1690
Golodyayev, Arseniy - LB1652
Golovko, Georgiy - LB1695
Gómez-Arias, Pedro J - LB1733
Gómez-García, Francisco J. - LB1733
Gómez-Garre, Dulcenombre - LB1733
Gong, Emily - LB1681, LB1691
Gonther, Sina - LB1635
Gonzalez, Jeanmarie - LB1714
Gopee, Hudaa - LB1781
Gorbunova, Vera - LB1794
Gotschall, Jeromy W. - LB1694
Grant, Sydney - LB1662
Gretzmeier, Christine - LB1660
Grimes, Graeme - LB1731
Grunfeld, Carl - LB1714
Gudjonsson, Johann - LB1670, LB1671, LB1674,
LB1703, LB1722
Guo, Sen - LB1644
Gutermuth, Jan - LB1713
Gyenesei, Attila - LB1721

H

Ha, Alex - LB1687
Haas, Allen - LB1683
Ham, Seoyoon - LB1789
Hamada, Yuko - LB1778
Hamang, Matthew - LB1747
Hammad, Zaid - LB1721
Hammers, Christoph M. – LB1644, LB1750
Han, Chann Makara - LB1719
Han, Hee Jeong - LB1704
Han, Jungmin - LB1738
Han, Lianyi - LB1741

Hanakawa, Sho - LB1637
Haniffa, Muzlifah - LB1674, LB1781
Hare, Michelle L. - LB1762
Harikrishnan, Nikhil - LB1681
Hariton, William V. - LB1644
Harn, Hans - LB1774
Harwood, Catherine - LB1663
Hasan, Fauad - LB1752, LB1753
Hasegawa, Akito - LB1717
Hasegawa, Ayami - LB1778
Häusler-Mehlhorn, Petra - LB1677
Healy, Eugene - LB1663
Heo, Chan Yeong - LB1680
Hermann, Nicola - LB1643
Hernawan, Ari - LB1648
Hertl, Michael - LB1636, LB1640, LB1798
Hervé, Bachelez - LB1726
Hillebrand, Greg - LB1652
Hinkston, Candice - LB1772
Hinterseher, Julia - LB1636, LB1640
Hippe, Daniel S. - LB1681, LB1691
Hoang, Phuong T. - LB1631, LB1633
Hobbs, Michael - LB1739
Hoboth, Peter - LB1661
Hoffman, Robert - LB1778
Honda, Tetsuya - LB1637
Hong, Yi-Kai - LB1724, LB1779
Hooper, Stephen R. - LB1679
Hornyak, Thomas J. - LB1766
Hosaka, Yuri - LB1785
Hou, Ping-Chen - LB1724
Howell, Michael - LB1752, LB1753
Hozak, Pavel - LB1661
Hsia, Edward - LB1786
Hsu, Chao-Kai - LB1724, LB1779
Hsu, Yu-Jou - LB1744
Hu, Chaoran - LB1702
Hu, Qiang - LB1662
Hu, Xing - LB1638
Hu, Yinin - LB1707
Hu, Zhengang - LB1638
Huang, Chen-Yu - LB1779
Huang, Ni - LB1781
Hudemann, Christoph - LB1798
Hundt, Jennifer E. - LB1644, LB1750
Hung, Chi-Feng - LB1744
Huss, Wendy J. - LB1662
Huygen, Lisa - LB1713
Huynh, Emily T. - LB1681, LB1690, LB1691
Hwang, Samual t. - LB1666
Hwu, Edwin En-Te - LB1712

I

Idrissi, Mariam - LB1754
Imamich, Tomozumi - LB1711
Inen, Jeffrey - LB1719
Inman, Gareth - LB1663
Inoue, Hideki - LB1785
Irvine, Alan D. - LB1687
Ishida, Yoshihiro - LB1637
Ishii, Tsuyoshi - LB1771
Iwamoto, Sadahiko - LB1639
Iyer, Jayasri - LB1690
Izmiryan, Araksya - LB1726

J

Jacobs, Jennifer - LB1708
Jang, Young Su - LB1676, LB1793
Jarell, Abel - LB1702
Jariwala, Nathan - LB1797
Jayarajan, Vignesh - LB1723
Jeon, Nooli - LB1668, LB1669
Jeong, Ga Hee - LB1757, LB1760
Jepsen, Rebecca - LB1700
Jesberg, Parker - LB1727
Jia, Huijue - LB1741
Jiang, Jingwei - LB1774, LB1792
Jiang, Liuyiqi - LB1741
Johnson, Courtney - LB1664

Johnston, Luke - LB1731
Joshi, Sandeep - LB1766
Juan-Cencerrado, Miguel - LB1733
Julia, Valérie - LB1670

K

Kabashima, Kenji - LB1637
Kabir, Ramisa F. - LB1659
Kaffenberger, Jessica - LB1684
Kahlenberg, Joanne M. - LB1671
Kalapurakal, Emmanual U. - LB1766
Kalidasan, Kamaladasan - LB1790
Kamal, Kanika - LB1682, LB1770
Kamata, Yayoi - LB1673
Kambala, Anusha - LB1751
Kang, Hee Young - LB1704
Kang, Jun - LB1689
Kang, Seunghyun - LB1680
Kao, Richard Y. - LB1737
Kartawira, Karin - LB1679
Kashiwakura, Jun-ichi - LB1711
Kasper, Maria - LB1674
Keh, Martin - LB1716
Keith, Yuki H. - LB1637
Kelly-Scumpia, Kindra M. - LB1787
Kerkmann, Urs - LB1697
Kerner, Amichai - LB1768, LB1769
Kerner, Miryam - LB1768, LB1769
Khanna, Urmi - LB1678
Khetterpal, Meenal - LB1708
Kida, Maki - LB1795
Kilgore, Samuel - LB1646
Kim, Arianna - LB1763
Kim, Dong Hyo - LB1649, LB1748
Kim, Dong Hyun - LB1676, LB1793
Kim, Hai Vin - LB1676, LB1793
Kim, Hoyoung - LB1668, LB1669
Kim, Hye Li - LB1675
Kim, Jin Cheol - LB1704
Kim, Joongnyon - LB1757, LB1760
Kim, Joung Soo - LB1773
Kim, Ki Chan - LB1757, LB1760
Kim, Lark Kyun - LB1675
Kim, Min Seo - LB1760
Kim, Seoyoung - LB1759
Kim, Su Min - LB1675
Kim, Sun Gyu - LB1773
Kim, Tae-Gyun - LB1675
Kim, Wan Jin - LB1675
Kim, Yeong Ho - LB1757
Kim, Yu Ri - LB1675
King, Brett - LB1697
Kiritsi, Dimitra - LB1660
Kiselev, Konstantin - LB1652
Klingelhutz, Aloysius J. - LB1743
Kobayashi, Satomi - LB1693
Koehler, Karl - LB1781
Kogut, Igor - LB1719, LB1727, LB1730
Komine, Mayumi - LB1639
Kong, Heidi H. - LB1738
Kong, Hyoun-Joong - LB1649
Kortekaas Krohn, Inge - LB1713
Koutsoukos, Stefanos A. - LB1730
Kozera, Emily - LB1700
Krishnaswamy, JK - LB1670
Krzikalla, Daria - LB1798
Kumthekar, Anand - LB1678
Kun, Jozsef - LB1721
Kwatra, Madan M - LB1751
Kwatra, Shawn G - LB1751
Kwon, Yoon Gyung - LB1748
Kwon, Youngji - LB1680

L

Lachance, Kristina - LB1681, LB1690
Laheurte, Caroline - LB1657
Laho, Kilian - LB1784
Lai, Chester - LB1663
Lai, Yung-Chih - LB1774

52

ISID 2023 Meeting – Late-Breaking AUTHOR INDEX
Laimer, Martin - LB1725
Laquer, Vivian - LB1702
Larouche, Danielle - LB1767
Lauffer, Felix - LB1677
Laughlin, Timothy L. - LB1762
Le, Doanh H. - LB1631, LB1633
LeBoeuf, Nicole - LB1686
Lecoester, Benoit - LB1657
Lee, Bernett - LB1637
Lee, Eng Sing - LB1740
Lee, Hanon - LB1748
Lee, Ji Hyun - LB1757, LB1760
Lee, Jimmy - LB1740
Lee, Ji Won - LB1649
Lee, John - LB1720
Lee, Ju Hee - LB1789
Lee, Julia Yu-Yun - LB1724
Lee, Jungseub - LB1669
Lee, Jun Hyo - LB1649, LB1748
Lee, Mikyung - LB1732
Lee, Sak - LB1676, LB1793
Lee, Sang Gyu - LB1789
Lee, Sohun - LB1680
Lee, Yonghee - LB1761
Lee, Young In - LB1789
Lee, Joohee - LB1789
Lee, Soyoung - LB1759
Lehloenya, Ranks - LB1801
Lei, Mingxing - LB1774, LB1792
Leigh, Irene - LB1663
Lejeune, Alexandre - LB1697
Leroux, Richard - LB1797
Leung, Bonnie W. - LB1686
Leung, Monica W. - LB1641
Li, Nick - LB1643
Li, Bingjie - LB1783
Li, Chia-Ling - LB1642
Li, Min - LB1729
Li, Ming - LB1729, LB1782
Li, Qinmenge - LB1671
Li, Xi - LB1701
Li, Yao - LB1709, LB1772
Li, Yueran - LB1801
Li, Zhiming - LB1741
Li, Zhiyang - LB1651, LB1653
Liao, En-Chih - LB1642
Liao, Hsien-Shun - LB1712
Lichtenberger, Beate M. - LB1674
Lim, Seong Soo - LB1740
Limbu, Susan - LB1780
Lin, Yu-Chen - LB1724
Lisa, Schweizer - LB1799
Lisco, Andrea - LB1738
Liu, Hong - LB1734
Liu, Huan - LB1654
Liu, Huawen - LB1792
Liu, Mengzhen - LB1720
Liu, Ran - LB1703
Liu, Xiao - LB1741
Liu, Yale - LB1800
Liu, Yingzi - LB1674
Lo, Sydeny - LB1758
Loh, Marie - LB1740
Lo Sicco, Kristen - LB1697
Lotti, Roberta - LB1750
Lozano, Ivonne - LB1791
Lucchesi, Jonathan - LB1747
Ludwig, Ralf J. - LB1644, LB1750
Luecken, Malte - LB1674
Luo, Yajun - LB1716
Lupp, Corinna - LB1677
Luther, Fabian - LB1645
Ly, Sophia - LB1770
Lymberopoulos, Eva - LB1739
Lytton, Simon D. - LB1634

M

Ma, Emily - LB1679, LB1707
Ma, Feiyang - LB1670
Ma, Li - LB1796

Ma, Yanfei L. - LB1747
Maeno, Hiroshi - LB1771
Maglie, Roberto - LB1634
Magne, Brice - LB1767
Maignan, Arielle - LB1706
Majmudar, Gopa - LB1652
Malfroy, Marine - LB1657
Mallal, Simon - LB1801
Malynn, Sandra - LB1641
Mambwe, Bezaleel - LB1797
Man, Mao-qiang - LB1714
Manjaly, Priya - LB1770
Mann, Matthias - LB1799
Manson Brown, Stephanie - LB1720
Marchetti, Michael A. - LB1707
Marconi, Alessandra - LB1750
Mardaryev, Andrei - LB1794
Margolis, David - LB1772
Marguier, Amelie - LB1657
Markale, Chinmay - LB1758
Martin, Joanne - LB1663
Martini, Jeff - LB1698
Matheson, Robert - LB1703
Matsumoto, Ayumii - LB1639
Mauro, Theodora M. - LB1714
Maury, Wendy - LB1743
Mc Entire, Jacquelyn - LB1747
McGarvey, Shennea - LB1730
McGrath, John A. - LB1724, LB1779
McGrath, Michael - LB1726
McGrath, Patrick S. - LB1719, LB1730
Medvecz, Márta - LB1721
Megan, Fitzgerald E. - LB1662
Mehta, Rahul - LB1720
Meloni, Marisa - LB1755
Menon, Ankita - LB1690
Menon, Siddarth - LB1786
Merola, Joseph F. - LB1702
Meskimen, Eric - LB1702
Messiaen, Ludwine - LB1656
Messingham, Kelly N. - LB1646, LB1743
Metzler, Barbara - LB1798
Meyer, Jason M. - LB1714
Meyer, Thomas - LB1776
Meyersburg, Damian - LB1634
Mina, Theresia - LB1740
Mirmirani, Paradi - LB1697
Mishra, Shreya - LB1665
Miyamoto, Kukizo U. - LB1762
Möbs, Christian - LB1636
Moh, Sang Hyun - LB1676, LB1793
Mohammed, Aabida - LB1786
Mohd Fadil, Muhammad Farhan B. - LB1788
Mohr, Cassandra - LB1709, LB1772
Möhrenschlager, Matthias - LB1685
Mondon, Phillipe - LB1797
Monteleon, Christine - LB1786
Montgomery, Brock - LB1764
Mora, Camilo - LB1687
Morina, Luke - LB1664
Mortazawi, Dariusch - LB1677
Mosch, Thomas - LB1677
Moshiri Yi, Yasman - LB1681
Mostaghimi, Arash - LB1682, LB1770
Moyes, Colin - LB1663
Mukherjee, Eric - LB1801
Müller, Eliane J. - LB1644
Murakami, Mitsuko - LB1662
Murase, Jenny - LB1687
Mussnig, Birgit - LB1634

N

Nagase, Kotaro - LB1690
Nagy, Nikoletta - LB1721
Nakamizo, Satoshi - LB1637
Nakamura, Yoshiyuki - LB1632
Nardin, Charlee - LB1657
Nash, Kalvin - LB1664
Naso, Gaetano - LB1723
Natalie, Chitra - LB1702

Natsuga, Ken - LB1724
Navsaria, Lucy - LB1683, LB1772
Ndao, Babacar - LB1657
Nead, Kevin - LB1683
Neller, Alexandra - LB1721
Neumann, Mareike - LB1635
Ngeow, Joanne - LB1740
Nghiem, Paul - LB1681, LB1690, LB1691
Nguyen, Macklin H. - LB1690
Nguyen, Nga - LB1686
Nie, Qing - LB1671, LB1672, LB1674
Nishiguchi, Tomoki - LB1717
Nomura, Toshifumi - LB1632
Nordenskjold, Magnus - LB1728
Nordmann, Thierry - LB1799
Nourse, Craig - LB1663
Novoa, Mónica - LB1791
Nowakowska, Malgorzata K. - LB1709
Nyström, Alexander - LB1660
Nørgaard, Laura O. - LB1712

O

O'Toole, Edel - LB1754
Obara, Koya - LB1778
Obeid, Joelle - LB1641
Oblong, John E. - LB1762
Oh, Honglyeol - LB1757, LB1760
Oh, Se Uk - LB1773
Ohta, Saki - LB1785
Okai, Bernard - LB1662
Okiyama, Naoko - LB1632
Ono, Sachiko - LB1637
Orfali, Raquel L. - LB1687
Osada, Aya - LB1693
Otero-Viñas, Marta - LB1795
Oya, Kazumasa - LB1632
Ozols, Matiss - LB1797

P

Pakhchanian, Haig - LB1706
Pal, Margit - LB1721
Palubinsky, Amy - LB1801
Pan, Chaolan - LB1782
Pan, Li - LB1766
Pappelbaum, Karin I. - LB1641, LB1776
Parada Cunza, Katia M. - LB1765
Paragh, György - LB1662
Parenteau, T. Richard - LB1714
Park, Jooyoung - LB1675
Park, Byoung Jun - LB1748
Park, Chang Ook - LB1675
Park, Ji Hun - LB1773
Park, Jungyoen - LB1680
Park, Kuiyoung - LB1732
Park, Kyung Min - LB1675
Park, Song - LB1691
Park, Sungwook - LB1758
Park, Young Joon - LB1704
Park, Young Min - LB1757, LB1760
Parvathaneni, Kaushik - LB1690
Parvathaneni, Upendra - LB1690
Paschke, Sophie - LB1739
Patel, Rhadika - LB1743
Patrick, Matthew T. - LB1671
Paus, Ralf - LB1776, LB1780
Pavlova, Maryna - LB1727, LB1730
Peng, Xueting - LB1800
Pereda, Jorge - LB1712
Pereira, Victor - LB1657
Peschard, Olivier - LB1797
Peter, Jonathan - LB1801
Peterson, Sherket - LB1720
Petkar, Mahir - LB1667
Pfützner, Wolfgang - LB1636
Phadungsaksawasdi, Pawit - LB1650
Phillips, Elizabeth J. - LB1801
Photowala, Huzefa - LB1703
Piccini, Ilaria - LB1777
Pierce, Evangeline - LB1702
Piketty, Christophe - LB1670

53

ISID 2023 Meeting – Late-Breaking AUTHOR INDEX
Pincelli, Carlo - LB1750
Pitois, Aurélien - LB1797
Plikus, Maksim - LB1671, LB1672, LB1674
Poh, Zhi Sheng - LB1788
Polakova, Alexandra - LB1636, LB1640
Pollmann, Robert - LB1636
Porter, Mireille - LB1801
Pradhan, Namrata - LB1710
Prieto-Sarmiento, Karol M. - LB1658
Proby, Charlotte - LB1663
Prodinger, Christine - LB1634, LB1725
Pujos, Muriel - LB1796
Pulliam, Thomas - LB1681
Purba, Talveen - LB1780

Q

Qamar, Mah - LB1663
Qasim, Waseem - LB1723
Qi, Quan - LB1653
Qu, Yulan - LB1716
Quaas, Alexander - LB1661
Quah, Shan - LB1659, LB1790

R

Radicchi, Débora C. - LB1660
Radine, Uta - LB1644
Rahimi, Siavash - LB1644
Rahmaniar, Wahyu - LB1648
Raiker, Rahul - LB1706
Rajeh, Ahmad - LB1751
Ram, Ramesh - LB1801
Ramakrishnan, Arulprakash - LB1745
Ramos, Raul - LB1672, LB1674
Ramot, Yuval - LB1697
Ran, Yuping - LB1647
Rashdan, Hannah - LB1686
Raun, Ellen - LB1712
Reddy, Pooja - LB1689
Reddy, Sriya V. - LB1751
Remenyik, Eva - LB1662
Remington, Allison J. - LB1681
Reppell, Mark - LB1720
Rescigno, Francesca - LB1755
Riboli, Elio - LB1740
Richards, Paige T. - LB1743
Rickaby, William - LB1663
Rider, Ashley - LB1630
Riley-Gillis, Bridget - LB1720
Ringenbach, Caroline - LB1797
Rivera-Ruiz, Irene - LB1733
Roh, Yoonjin - LB1732
Roop, Dennis R. - LB1730, LB1735
Rorteau, Julie - LB1784
Rosenbach, Misha - LB1687
Rouillé, Thomas - LB1777
Rovito, Holly A. - LB1762
Rozati, Sima - LB1689
Rozhkova, Elena - LB1794, LB1795
Ruano, Juan - LB1733
Rundle, Chandler - LB1708
Ryan, Russell - LB1665
Ryeom, Gyoseon G. - LB1680

S

Sadik, Christian D. - LB1635
Saito, Yuki - LB1717
Sakurai, Tetsuhito - LB1673
Saleem, Mohammad - LB1656
Sampath, Prabha - LB1659, LB1790
Samuel, Christeen - LB1689
Sanchez, Katherine - LB1770
Sánchez-González, Silvia - LB1733
Sanchez Lopez, Jeannie - LB1765
Sarkar, Mrinal K. - LB1722
Sato, Yasunari - LB1771
Satoh, Masahiko - LB1673
Satzinger, Sabrina - LB1715
Schadeck, Tobias - LB1677

Schäkel, Knut - LB1641
Schärli, Stefanie - LB1645
Scharschmidt, Tiffany C. - LB1714
Schilf, Paul - LB1635
Schlapbach, Christoph - LB1645
Schlievert, Patrick - LB1646
Schmid-Grendelmeier, Peter - LB1685
Schneider-Burrus, Sylke - LB1776
Schoenherr, Christina - LB1663
Schwartz, Rachel - LB1678
Scumpia, Philip O. - LB1787
Sebastiano, Vittorio - LB1786
Segre, Julia A. - LB1738
Seluanov, Andrei - LB1794
Semenov, Yevgeniy - LB1686
Seo, Da Hye - LB1676, LB1793
Seo, Hyun-Min - LB1773
Seo, Seongjun - LB1732
Seol, Hyeonjeong - LB1680
Sereti, Irini - LB1738
Seykora, John T. - LB1771
Sha, Wen - LB1651
Shaikh, Mustufa - LB1747
Shalin, Sara - LB1688
Shang, Lily - LB1787
Sharafeldin, Noha - LB1656
Sharma, Nikhil - LB1739
Sharov, Andrey - LB1794, LB1795
Shekhar, KC - LB1710
Shen, Xinyu - LB1792
Sherratt, Michael J. - LB1797
Shettigar, Nitish - LB1672
Shi, Linyu - LB1703
Shim, Soonmi - LB1718
Shim, Mikang - LB1668, LB1669
Shin, Daniel B. - LB1694
Shin, Jung U - LB1676, LB1793
Shirai, Kyoumi - LB1778
Shrestha, Elisha - LB1710
Shtanko, Olena - LB1743
Silke, John - LB1799
Silva Simoes, Luiza - LB1658
Simon, Jan-Christoph - LB1775
Simon, Scott - LB1666
Simpson, Cory L. - LB1722
Sinclair, Rodney - LB1697
Singh, Prashant - LB1662
Sivaloganathan, Darshan M. - LB1751
Small, Alison - LB1698
Smaoui, Nizar - LB1720
Smith, Brandon - LB1709
Smith, Graham - LB1630
Smith, Payton L. - LB1688
Sockler, Patrick G. - LB1679
Solhjoo, Soroosh - LB1664
Sonkoly, Enikö - LB1674
Sorkin, Dara - LB1674
Soung, Jennifer - LB1702
Spice, Jordan - LB1786
Stadler, Pia C. - LB1799
Steck, Oliver - LB1645
Stefanovic, Nicholas - LB1687
Steinhoff, Ana - LB1777
Steinhoff, Martin - LB1667
Su, Wenrou - LB1783
Subramanian, Gowtham - LB1790
Suga, Yasushi - LB1673
Suh, Dae Hun - LB1649, LB1748
Sun, Sukkyu - LB1649
Sun, Yao - LB1701
Sunarwidhi, Anggit L. - LB1648
Suzuki-Horiuchi, Yoko - LB1771
Sweren, Ronald - LB1664
Syu, Li-Jyun - LB1665
Szell, Marta - LB1721
Sztacho, Martin - LB1661

T

Tachiki, Lisa - LB1681
Takamori, Kenji - LB1673
Takamoto, Kazumori - LB1692
Takaoka, Nanako - LB1778
Takeshita, Junko - LB1694
Tan, Yimei - LB1701, LB1741
Tandukar, Bishal - LB1766
Tang, Qu - LB1792
Tapia-Paez, Isabel - LB1728
Tay, Darwin - LB1740
Taylan, Fulya - LB1728
Taylor, Emma - LB1765
Teng, Joyce M. - LB1698
Terhune, Julia H. - LB1707
Thang, Christopher J. - LB1695
Thangaveloo, Moogaambikai - LB1788
Theodosakis, Nicholas - LB1682, LB1770
Thepot, Amelie - LB1784
Thiboutot, Diane - LB1748
Thirunavukkarasu, Kannan - LB1747
Thng, Steven T. - LB1740
Thomas, Devon - LB1695
Thomson, Jason - LB1663
Thys, Pauline Marie - LB1713
Thyssen, Jacob - LB1645, LB1687
Tian, Shenghua - LB1783
Timp, Winston - LB1664
Tiwaa, Afua - LB1722
Tlyachev, Timur - LB1652
Toichi, Eiko - LB1692
Toker, Michelle - LB1678
Tominaga, Mitsutoshi - LB1673
Tong, Lingying - LB1756
Torabi, Fereshteh - LB1781
Tordesillas, Leticia - LB1658
Torisu-Itakura, Hitoe - LB1702
Torregrossa, Marta - LB1775
Torres-Pradilla, Mauricio - LB1791
Toyama, Sumika - LB1673
Treanor-Taylor, Mairi - LB1663
Treat, James - LB1698
Trompezinski, Sandra – LB1784
Trubiano, Jason - LB1801
Trujillo, Maribel - LB1791
Tsai, Kenneth - LB1658
Tsianakas, Athanasios - LB1641
Tsoi, Lam - LB1671, LB1674
Tsuda, Hidetoshi - LB1639
Tsujihana, Kojiro - LB1692
Tu, Wei-Ting - LB1724

U

Urban, Peter - LB1721

V

Van Delm, Wouter - LB1670
Velmurugan, Kalpana - LB1727
Verma, Navin K. - LB1788
Veves, Aristidis - LB1794
Viola, Joana R. - LB1776
Vires, Laura - LB1762
Viveiros, Matthew - LB1684
Volkmann, Karolin - LB1636, LB1640
Vorholt, Julia - LB1654
Vu, Luong H. - LB1631, LB1633

W

Wahlgren, Carl-Fredrik - LB1728
Wajsbrot, Dalia - LB1697
Walker, Patricia S. - LB1752, LB1753
Wan, Guihong - LB1686
Wan, Huiying - LB1736
Wan, Joy - LB1679
Waner, Milton - LB1698
Wang, Feifei - LB1783
Wang, Fudi - LB1651, LB1653

54

ISID 2023 Meeting – Late-Breaking AUTHOR INDEX
Wang, Jen-Hung - LB1712
Wang, Jiucun - LB1741, LB1742
Wang, Jun - LB1663
Wang, Mengyue - LB1774, LB1792
Wang, Sailan - LB1728
Wang, Sheng-Pei - LB1687
Wang, Sijia - LB1651, LB1653, LB1783
Wang, Xiaojie - LB1672
Wang, Xiaoxiao - LB1782
Wang, Yumeng - LB1729
Waring, Jeffrey - LB1720
Wasikowski, Rachael - LB1671
Watanabe, Kazuhisa - LB1639
Watson, David - LB1630
Watson, Rachel E. - LB1797
Watt, Fiona M. - LB1674
Wearne, Stephen J. - LB1740
Wegner, Sven - LB1641
Wehner, Mackenzie - LB1683, LB1709, LB1772
Wei, Lei - LB1662
Wei, Maria L. - LB1687
Wei, Qingzhen - LB1741
Weidinger, Stephan - LB1677
Weinstein, Jason S. - LB1787
Werner, Sabine - LB1654
Wespiser, Mylène - LB1657
Whelan, Chris - LB1658
Whipman, James - LB1654
White, Anna - LB1643
Whitesell, Caslyn - LB1747
Wiedemann, Julie - LB1674
Wilbert, Dawn - LB1665
Willenborg, Sebastian - LB1715
Wollenberg, Andreas - LB1713
Wong, Martin - LB1765
Wu, Benedict - LB1678
Wu, Chyuan-Chuan - LB1724
Wu, Jiani - LB1651
Wu, Muzhou - LB1795
Wu, Rong - LB1665
Wu, Shiyong - LB1756
Wu, Wang - LB1774, LB1792

Z

Zaba, Lisa - LB1681
Zawacki, Lauren - LB1681
Zeiser, Robert - LB1660
Zepeda Reyes, David E. - LB1765
Zhang, Furen - LB1734
Zhang, Jinwei - LB1774, LB1792
Zhang, KeLun - LB1675
Zhang, Shijia - LB1686
Zhang, Si - LB1729
Zhao, Anqi - LB1729
Zhao, Yi - LB1696
Zheng, Ashley - LB1764
Zheng, Xiuwen - LB1720
Zhenji, Zhu - LB1632
Zhong, Qian - LB1741
Zhou, Wei - LB1792
Zhou, Yi - LB1742
Zhu, Yucui - LB1763
Ziadlou, Reihane - LB1643
Zondler, Lisa - LB1641
Zwillich, Samuel - LB1697

X

Xia, Jingjing - LB1741, LB1742
Xia, Yumin - LB1800
Xiang, David H. - LB1682
Xianghong, Yan - LB1762
Xu, Daniel - LB1747
Xu Landén, Ning - LB1674

Y

Yan, Li - LB1662
Yan, Zhenzhen - LB1734
Yang, Li - LB1774, LB1792
Yang, Min-Chia - LB1724
Yao, Zhirong - LB1782
Yen, Chung-Yang - LB1749
Yew, Yik Weng - LB1740
Yildiz, Selin - LB1725
Yonekura, Satoru - LB1692
Yoon, Ji Young - LB1748
Yoshino, Takashi - LB1673
Young, Katherine - LB1682
Yu, Alina - LB1747
Yu, Sheng-Jie - LB1749
Yuan, Hao - LB1674
Yusuf, Nabiha - LB1656

55

ISID 2023 Meeting – Late-Breaking KEYWORD INDEXA

Acne LB1649, LB1748, LB1770
Adhesion LB1644, LB1793
Aging LB1651, LB1652, LB1653, LB1668, LB1669,
LB1680, LB1696, LB1711, LB1714, LB1730,
LB1741, LB1761, LB1762, LB1771, LB1783,
LB1785, LB1786, LB1788, LB1792, LB1796,
LB1797
AI (Artificial Intelligence) LB1648, LB1649, LB1650,
LB1651, LB1652, LB1653, LB1799
Allergy LB1685, LB1731
Alopecia LB1667, LB1697, LB1733, LB1777
Apoptosis LB1717
Appendages LB1774, LB1792
Atopic Dermatitis LB1635, LB1637, LB1645, LB1675,
LB1677, LB1679, LB1685, LB1687, LB1694,
LB1702, LB1712, LB1728, LB1731, LB1736,
LB1737, LB1739, LB1740, LB1744, LB1751
Autoimmunity LB1632, LB1633, LB1634, LB1636,
LB1640, LB1642, LB1644, LB1646, LB1685,
LB1728, LB1746, LB1750, LB1798
Autoinflammatory Diseases LB1678

B

Barrier Function LB1635, LB1712, LB1713, LB1714,
LB1715, LB1718, LB1723, LB1754
Basal Cell Carcinoma LB1763
Basement Membrane LB1660
B Cells LB1700
Biochemistry LB1699
Bioinformatics LB1630, LB1648, LB1671
Biologics LB1630, LB1667, LB1692
Biomechanics LB1666
Blistering Disease LB1640, LB1644, LB1684,
LB1722, LB1724, LB1730, LB1798, LB1800,
LB1801
Bullous Disease LB1634, LB1636, LB1646, LB1684

C

Cancer Biology LB1654, LB1657, LB1658, LB1659,
LB1678, LB1735, LB1746, LB1756
Cancer Genetics LB1656, LB1665
Carcinogenesis LB1656, LB1662, LB1665
Cell Adhesion LB1666
Cell-Based Therapy LB1723, LB1767, LB1779
Cell Biology LB1654, LB1661, LB1664, LB1716,
LB1771, LB1789, LB1796
Cell Migration LB1790
Chemokines LB1792
Clinical Research LB1677, LB1686, LB1687, LB1690,
LB1692, LB1693, LB1698, LB1701, LB1707,
LB1708, LB1709, LB1712, LB1716, LB1770
Clinical Trials LB1636, LB1680, LB1700, LB1703,
LB1765Collagen LB1670, LB1676, LB1761
Connective Tissue Diseases LB1631, LB1727
Contact Sensitivity LB1650
Cutaneous T Cell Lymphoma (CTCL) LB1664
Cytokines LB1645, LB1711, LB1732

D

Desmosomes LB1722
Drug Development LB1648, LB1659, LB1744,
LB1750, LB1753, LB1790
Drug Reactions LB1689, LB1695, LB1773, LB1799

E

Eccrine Glands LB1706
Eczema LB1694
Endothelial Cells LB1781
Eosinophils LB1689
Epidemiology LB1651, LB1683, LB1769, LB1772
Epidermolysis Bullosa LB1724, LB1725, LB1779,
LB1791
Epigenetics LB1638, LB1740, LB1763, LB1783,
LB1786, LB1795
Evolutionary Development (Evo-Devo) LB1658
Extracellular Matrix LB1755, LB1794, LB1797

G

Gene Regulation LB1729
Gene Therapy LB1719, LB1723
Genetic Diseases LB1688, LB1698, LB1719, LB1721,
LB1722, LB1724, LB1725, LB1726, LB1727,
LB1729, LB1754, LB1782
Genetics LB1783
Gene Transcription LB1663
Genodermatoses LB1725
Genome-Wide Association Studies (GWAS) LB1653,
LB1720
Genomics LB1674, LB1739

H

Hair Biology LB1647, LB1672, LB1680, LB1766,
LB1773, LB1774, LB1777, LB1778, LB1780,
LB1782
Health Services Research LB1707, LB1709
Hidradenitis Suppurativa LB1700, LB1776

I

Ichthyosis LB1715
Imaging LB1647, LB1649, LB1652, LB1661
Immunity, Adaptive LB1787, LB1801
Immunity, Innate LB1656, LB1726
Immunodeficiencies LB1734, LB1738
Immunology LB1632, LB1635, LB1657, LB1667,
LB1699, LB1720, LB1735
Immunomodulatory Therapy LB1634, LB1641,
LB1677, LB1684, LB1686, LB1689, LB1787
Immunotherapy LB1638, LB1643, LB1657, LB1681,
LB1686, LB1691
Induced Pluripotent Stem (iPS) Cells LB1673
Infection, Bacteria LB1732, LB1734, LB1737
Infection, Fungal LB1647, LB1757
Infection, Viral (non-HIV/HPV) LB1743
Inflammation LB1642, LB1695, LB1699, LB1714,
LB1732, LB1737, LB1745, LB1748, LB1749,
LB1762, LB1775, LB1780
Inflammatory Skin Diseases LB1678, LB1682,
LB1703, LB1733, LB1744, LB1751, LB1752,
LB1780Interleukins LB1641
Interventional Trials LB1704
Itch LB1673

K

Keratinization Disorders LB1729, LB1754
Keratinocyte Biology LB1711
Keratinocyte Differentiation LB1774, LB1795
Keratinocytes LB1670, LB1671, LB1683, LB1716,
LB1717, LB1731, LB1741, LB1743, LB1772,
LB1793
Keratins LB1785

M

Macrophages LB1639, LB1781
Mast Cells LB1637
Matrix Biology LB1664, LB1784
Melanocytes LB1721, LB1766
Melanoma LB1638, LB1707, LB1764, LB1772
Merkel Cell Carcinoma LB1681, LB1690, LB1691
Metabolism LB1676, LB1715
Metabolomics LB1742
Metastasis LB1659
Methods/Tools/Techniques LB1674, LB1690,
LB1701, LB1706, LB1710, LB1713, LB1742,
LB1759, LB1776
Microbiome LB1646, LB1733, LB1738, LB1739,
LB1740, LB1741, LB1742
Microscopy LB1661, LB1668, LB1669
Models LB1668, LB1669, LB1727, LB1743, LB1750,
LB1758, LB1776, LB1777, LB1781, LB1784
Models, Animal LB1747, LB1753
Models, Mouse LB1665, LB1747, LB1775, LB1798

N

Neurobiology LB1673
Neurophysiology LB1758
Neutrophils LB1639, LB1666

O

Oncogenes LB1660

P

Patient Outcomes Research LB1681, LB1695,
LB1704
Pediatrics LB1679, LB1688, LB1694
Pharmacology LB1698, LB1745, LB1746, LB1751,
LB1752
Photobiology LB1662, LB1756, LB1758, LB1759,
LB1767
Photochemistry LB1756
Photodynamic Therapy LB1662
Pigmentation and Pigment Cell Biology LB1682,
LB1688, LB1704, LB1721, LB1765, LB1766,
LB1767, LB1771
Protein Kinase C (PKC) LB1765
Proteomics LB1755, LB1799
Pruritus LB1670
Psoriasis LB1630, LB1639, LB1641, LB1692,
LB1693, LB1703, LB1726, LB1745, LB1749,
LB1753Public Health Research LB1679, LB1682, LB1683,
LB1687, LB1709, LB1770

R

Regenerative Medicine LB1719, LB1797
Retinoids LB1759
Rosacea LB1720

S

Scar LB1789, LB1794
Scleroderma LB1631, LB1747
Signaling LB1671, LB1748, LB1752
Signal Transduction LB1717, LB1763
Squamous Cell Carcinoma LB1658, LB1660,
LB1663, LB1730
Stem Cells LB1672, LB1778, LB1779, LB1788

T

T Cells LB1632, LB1640, LB1642, LB1645, LB1735,
LB1749, LB1801
Tissue Regeneration LB1672, LB1786
Transcription LB1663
Tumor Biology LB1654

U

UV Radiation LB1755, LB1757, LB1760, LB1761,
LB1762, LB1768

V

Vaccines LB1702
Vitiligo LB1643

W

Wnt Signaling LB1775
Wound Healing LB1778, LB1784, LB1785, LB1787,
LB1788, LB1789, LB1790, LB1793, LB1794,
LB179556