Program and Abstracts

PAPSBRSThe 11th Annual Congress of Pan Asian-Pacific
Skin Barrier Research Society

ISID 2023 Tokyo Satellite Symposium

May 10 (Wed), 2023 / 12:00-14:45
Venue : Harmony, 44F Keio Plaza Hotel, Tokyo
Date :

President :Yutaka Hatano, M.D., Ph.D. Department of Dermatology, Faculty of Medicine, Oita University
Vice-President :Yutaka Takagi, Ph.D. Faculty of Pharmaceutical Sciences, Josai University

Secretary-General & Society Secretariat :Takashi Sakai, M.D., Ph.D. Department of Dermatology, Faculty of Medicine, Oita University

The 11th Annual Congress of Pan Asian-Pacific Skin Barrier Research Society (PAPSBRS)Luncheon Special LectureDate：Wednesday, May 10, 2023 / 12:05-12:50
Venue：Harmony, 44F Keio Plaza Hotel Tokyo
2-2-1 Nishi-Shinjuku, Shinjuku-Ku, Tokyo 160-8330

Theme

Skin permeability barrier formation
by ceramides

Chair

Dr. Toshifumi Nomura

SpeakerDr. Akio Kihara

Professor and Chair, Department of Dermatology,
Institute of Medicine, University of Tsukuba

Professor, Faculty of Pharmaceutical Sciences,
Hokkaido University

Co-sponsored: The 11th Annual Congress of Pan Asian-Pacific Skin Barrier Research Society (PAPSBRS)Sanofi K.K.

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Skin Barrier Research Society
PAPSBRS Overview

President of Pan-Asian Pacific Skin Barrier Society (PAPSBARS)
President: M ao-Qiang Man (Dermatology Service Veterans Affairs Medical Center, Department of Dermatology,
University of California, San Francisco, USA; Dermatology Hospital of Southern Medical University, China)
Honorary President: Seung H. Lee
Honorary President: Peter M. EliasInternational board members and contributors for conference programming
Eung Ho Choi (President of Korean Society for Investigative Dermatology; Yonsei University Wonju College of Medicine, Korea)
John Common (President of Skin Research Society of Singapore; A*STAR Skin Research Labs, Singapore)
Li He (Kunming Medical University, China)
Haekwang Lee (President of Korean Society for Skin Barrier Research; P&K Skin Research Center, Korea)
Hyun-Jung Kim (Chairperson of Korean Society for Skin Barrier Research; Chungnam National University, Korea)
Sekyoo Jeong (Vice president of Korean Society for Skin Barrier Research; Incospharm Corp, Korea)
Chih-Hung Lee (Kaohsiung Chang Gung Memorial Hospital, Taiwan)
Tzu-Kai Lin (Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan)
Jason M. Meyer (Vanderbilt University Medical Center, USA)
Tingting Zhu (Soochow University, China)

Organizing and host program committee members in the 11th PAPSBARS
President: Yutaka Hatano (Oita University, Japan)
Vice president: Yutaka Takagi (Josai University, Japan)
Secretary general: Takashi Sakai (Oita University, Japan)
Masashi Akiyama (Nagoya University, Japan)
Akemi Ishida-Yamamoto (Asahikawa Medical University, Japan)
Akiharu Kubo (Kobe University, Japan)
Shin Morizane (Okayama University, Japan)
Toshifumi Nomura (University of Tsukuba, Japan)
Yasuko Obata (Hoshi University, Japan)
Shigetoshi Sano (Koch University, Japan)
Yoshikazu Uchida (Hallym University, Korea)

Please note that registration for ISID2023 is mandatory for participation in the 11th PAPSBRS.
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Skin Barrier Research Society
PAPSBRS Overview

WELCOME

President of PAPSBRS: Mao-Qiang Man (Dermatology Service Veterans Affairs Medical
Center, Department of Dermatology, University of California, San Francisco, USA;
Dermatology Hospital of Southern Medical University, China)

Dear Colleagues
More and more evidence has shown the crucial role of epidermal permeability barrier function in regulation of cutaneousand extracutaneous function. Epidermal dysfunction contributes, at least in part, to the development of inflammatory skindisorders and some systemic disorders. Understanding the underlying mechanisms and the efficacy of products that
regulate epidermal permeability barrier will advance the development of approaches in the management of epidermal
permeability barrier dysfunction and its associated disorders. In these aspects, much progress has been made over the
recent years. We all know that meeting provides an incomparable opportunity for scientists to exchange informationin their research, in addition to meeting their old friend and making new ones. However, we have missed three annual
meetings due to the COVID pandemic. Finally, we have this opportunity to meet again at the 11th annual meeting of PanAsian Pacific Skin Barrier Research Society (PAPSBRS) in Tokyo, Japan.
On behalf of the PAPSBRS, it is with great pleasure that I welcome you to enjoy the exciting meeting and beautiful
scenery on May 10, 2023, in Tokyo. Also, I would like to express my sincere appreciation to the members of meetingorganizing committee, especially professor Yutaka Hatano at Oita University, for their efforts in organizing this event. I
am extremely grateful to the speakers for their generosity and willingness to share their work with us at the meeting. I amvery thankful to attendees for their participation.
Once again, I sincerely welcome you to the 11th PAPSBRS meeting. I hope you will enjoy both the scientific program andscenery of Tokyo, and appreciate the opportunity to connect with friends.

Sincerely yours,
Mao-Qiang Man, MD.
The president of PAPSBRS

2WELCOME

President of the 11th PAPSBARS: Yutaka Hatano (Oita University, Japan)

Dear Friends and Colleagues,
It is my great pleasure to welcome you to the 11th Annual Congress of the Pan Asian–Pacific Skin Barrier ResearchSociety (PAPSBRS) on May 10, 2023, in Tokyo. In fact, this conference was scheduled to be held in Nagoya in December
2020, as a satellite of the 45th Annual Meeting of the Japanese Society for Investigative Dermatology. However, we
decided to cancel the event because we considered that the purpose of the conference was to be a platform forcolleagues, researchers, and friends to meet face-to-face to share our academic research and enjoy being among
friends. Thanks to plenty of encouragement, contributions, and help from our friends and colleagues, we decided to holdthis conference and finally get together in Tokyo to discuss science and renew our connections. Although the conference
is much smaller than it used to be, we can look forward to hearing interesting lectures regarding important scientifictopics. These lectures reflect that skin barrier function research covers a wide range of areas such as permeability,
antibacterial properties, and immunity and is closely related to various physiological phenomena, including itch,
inflammation, and immunity, among others. In addition, understanding skin barrier function improves our understandingof various diseases, and is becoming an important and attractive field for both researchers and clinicians. We hope that
all attendees will enjoy the conference and contribute to the development of this field. I also hope that this conference
will bring together skin barrier researchers from around the world and serve as an inspiration for young researchers. I
would like to express my sincere gratitude to all those who were involved in the preparation of this conference.

Sincerely yours,
Yutaka Hatano, MD, PhD
Professor and Chairman,
Department of Dermatology,
Faculty of Medicine,
Oita University3

of The 11th Annual Congress of Pan Asian-Pacific
Skin Barrier Research Society
PAPSBRS Overview

WELCOME

Vice President of the 11th PAPSBARS: Yutaka Takagi (Josai University, Japan)

Dear Friends and Colleagues
It is a great pleasure to have the 11th Annual Congress of Pan Asian-Pacific Skin Barrier Research Society as ISID 2023
Tokyo Satellite Symposium. I am very happy that we can gather and discuss about skin barrier function with manyfriends and colleagues from many countries over the COVID-19 disaster.
About 30 years ago, I started to study cutaneous barrier function in Dr. Elias Group. On that time, I belonged to acompany and tried to develop and launch skin-care products which enhance cutaneous permeability barrier function.
Many people recognized that cutaneous barrier is important and some severe cutaneous disease cause barrier
perturbation, however, they believed that most people had healthy barrier function and no need a particular care. Thus, it
was quite hard to convince of the importance of taking care of barrier function with skin care materials.
In the last thirty years, various new findings about cutaneous barrier function have been reported by many researchers.
The tight junction in the epidermis, the relationship between permeability barrier and immune system, importance ofskincare on neonatal period to prevent development of atopic dermatitis, and so on. Of cause, the research about
ceramides, one of the crucial factors of barrier function, have made great progress, such as ceramide components areanalyzed in detail generally, the metabolism of ceramides becomes clearly including the finding of metabolizing enzymes,
and various functions of sphingolipids on cutaneous metabolism have been reported. Accompanied with these findings,
the awareness of people about the importance of cutaneous barrier function have been increased and many people
worry about their own and family’s cutaneous barrier conditions.
Fortunately, I could attend the predecessor meetings of PAPSBRS, Korean Symposium of Skin Barrier Research (KSSBR),
1st annual congress of PAPSBRS in Dalien in China (in this congress, only Prof. Hatano and I were Japanese participants).
I am very grad that this PAPSBRS is expanding more and more and there are many exciting presentation and reports on
this 11th congress. I believe that all of you will be able to enjoy this congress and connect to further development of yourresearch.
Vice President, Yutaka Takagi, Ph.D.
Professor, Department of Pharmaceutical Sciences
Josai University

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WELCOMEInternational board members and contributors for conference programming: Haekwang Lee(President of Korean Society for Skin Barrier Research; P&K Skin Research Center,
Korea)As a president of Korean Society for Skin Barrier Research, I would like to express my sincere gratitude to Professor
Yutaka Hatano, Professor Takashi Sakai, and all the other members of program committee for organizing the 11 th
Annual Congress of Pan-Asian Pacific Skin Barrier Research Society. During the last a few years, all of us suffered theunprecedented world-wide pandemic situation and missed many academic events, including PAPSBRS. However, thisyear, with invaluable efforts by Japanese members, we can re-start the congress again and I’m so honored to be able togive a message for this congress. The PAPSBRS congress is not only an academic meeting, but also a great platform
for social gathering and networking for barrier research members. It continues to grow up both in quality and numbersof participants, and I am sure that PAPSBRS is a cornerstone event for every skin barrier research member. Now skinbarrier function is considered as a keyword for investigative dermatologist and cosmetic researchers, and we will keep
our best efforts to make this event being open for every participant and, most of all, to stimulate the research for skinbarrier function. Again, I would to appreciate all of the program committee members for their efforts and sincerely hopethat all of the participants can enjoy this event.
Haekwang Lee
President of Korean Society for Skin Barrier Research; P&K Skin Research Center, Korea

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Skin Barrier Research Society
PAPSBRS Overview

WELCOMEInternational broad members and contributors for conference programming: John Common(President of Skin Research Society of Singapore; A*STAR Skin Research Labs,
Singapore)
It is my great pleasure to give a warm welcome to all the participants of the 11th Annual Congress of the Pan AsiaPacific Skin Barrier Research Society (PAPSBRS). We are delighted to be hosting another Congress of PAPSBRS afteran enforced break during the pandemic, and as the board member representing Singapore, I hope that all the delegates
attending enjoy the science and discussions.
This congress provides a unique forum for the Asia-Pacific region, bringing together research scientists, clinician
scientists and our colleagues from industry, with a shared interest in skin barrier research. We are continuing to witness
a steady growth of interest in the skin as a research system and there are many new and fascinating topics emerging
in barrier research that highlights the complexity and intricacy of our connection with the external environment. The
PAPSBRS Congress hopes to capitalize on this interest in the skin barrier and provide research lectures that offer up-todate information with a broad interest and strong lean towards translational research.
Many people have worked very hard to get this PAPSBRS Annual Congress together and I thank them all sincerely for
their efforts. We are also very fortunate that the format of the ISID allows for dedicated satellite symposia, providing afantastic opportunity to get together again, in person, to passionately share our new research on the skin barrier. It would
therefore not be possible without the amazing work of the ISID organizers that provide the foundations for all the satellite
symposia that are taking place adjunct to the main meeting this year. Singapore is a proud member of the PAPSBRS and
we hope that many other members will join us in the future.
John Common
Senior Principal Investigator, A*STAR Skin Research Labs, Singapore
President, Skin Research Society of Singapore
Board member and Singapore representative, PAPSBRS

6WELCOMEInternational board members and contributors for conference programming: Chih-Hung Lee(Professor, Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital,
Kaohsiung, Taiwan)
A message to the investigators and attendees for the 11th Pan Asian Pacific Skin Barrier Research Symposium (PAPSBRS)Skin is the largest organ that delineates the boundary between host body and the environment. Skin barrier integrity andits function are vital to the skin homeostasis in different physiological aspects, including immune networks, environmental
interactions, neurovascular regulations, and etc. Hence, abnormal skin barrier contributes to the pathophysiologicalprocess in a variety of skin diseases, including environmental skin diseases, allergic skin diseases, infections skindisease, and so on. In parallel, as a large reservoir, skin provides a useful model for drug absorption and delivery. These
unique features of skin barrier grant the skin barrier research a great platform for the interdisciplinary investigations. With
fruitful collaborations and discussions among the investigators and attendees from different disciplines, I am sure the11th PAPSBRS will be a huge success, not only to foster the collaborations but also to harvest the young investigators.
Chih-Hung Lee, MD, PhD
Professor, Department of Dermatology, Kaohsiung Chang Gung Memorial
Hospital, Kaohsiung, Taiwan

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PAPSBRS Overview

WELCOMEInternational board members and contributors for conference programming: Jason M. Meyer(Vanderbilt University Medical Center, USA)
Message for the 11th Annual Pan Asian-Pacific Skin Barrier Research Society(PAPSBARS) Symposium

Dear Colleagues and Friends,
I am honored to accept an invitation to share my research at the 11th Annual Pan Asian-Pacific Skin Barrier ResearchSociety Symposium. My interest in the skin barrier stems from my clinical work as a dermatologist and my laboratory
research on skin barrier formation. Recently, I have contributed to a research project with Dr. Alan Brash at Vanderbilt
University to study the enzymatic activity of PNPLA1, a protein that is essential for skin barrier function via its role inceramide and fatty acid metabolism. I hope you will find this research project as interesting and enjoyable as I have.
This project is part of a larger research effort carried out by many investigators across the world to define the molecularbasis of skin barrier function (and dysfunction). My former postdoctoral mentor, Dr. Peter Elias, told me a few years agothat there has never been a better time to be involved in skin barrier research, based on a decades-long solid foundation
plus a promising future with many opportunities for applications to medicine and industry. This 11 th PAPSBARS
Symposium promises to provide an engaging snapshot of the current field, with representatives from across the world
and from diverse backgrounds and areas of expertise. I am very excited to be part of this symposium, and I’m looking
forward to my first trip to Japan, to seeing old friends and making new acquaintances. See you soon in Tokyo!

Sincerely,
Jason Meyer, MD, PhD
Instructor and Attending Physician
Vanderbilt Dermatology
Nashville VA Medical Center
Nashville, TN, USA8

Schedule and Program of The 11th Annual Congress of Pan Asian-Pacific Skin
Barrier Research Society (PAPSBRS)
Date: May 10, 2023
Venue: KEIO PLAZA HOTEL TOKYO (room: Harmony 44F)
10:00-11:00 Business meeting (room: Comet 43F)
12:00-12:03 Opening remarks:
Yutaka Hatano (President of the 11th PAPSBARS; Oita University, Japan)
12:05-12:50 Luncheon Special Lecture (Lecture 40min; Q&A 5min.) *sponsored by Sanofi K.K.
Title: Skin permeability barrier formation by ceramides
Speaker: Akio Kihara (Hokkaido University, Japan)
Chair: Toshifumi Nomura (University of Tsukuba, Japan)
Short Break
12:53-13:11 Lecture 1 (Presentation 15min. Q&A 3min.)Title: Purified recombinant PNPLA1 catalyzes the synthesis of acylceramides and acylacids of the
mammalian skin barrier
Speaker: Jason M. Meyer (Vanderbilt University Medical Center, USA)
Chair: Matthias Schmuth (Medical University Innsbruck, Austria)
13:11-13:29 Lecture 2 (Presentation 15min. Q&A 3min.)Title: Antimicrobial peptides enhance skin barrier function: therapeutic implications in atopic dermatitis
Speaker: François Niyonsaba (Juntendo University, Japan)
Chair: Shin Morizane (Okayama University, Japan)
13:29-13:47 Lecture 3 (Presentation 15min. Q&A 3min.)Title: Topical autophagy activator enhances the epidermal permeability barrier function through
SIRT1-mediated ceramide synthesis
Speaker: Sekyoo Jeong (Incospharm Corp, Korea)
Chair: Haekwang Lee (P&K Skin Research Center, Korea)
Short Break
13:50-14:08 Lecture 4 (Presentation 15min. Q&A 3min.)Title: Laser-mediated drug delivery to overcome the skin permeation barrier
Speaker: Jia-You Fang (Chang Gung University, Taiwan)
Chair: Chih-Hung Lee (Kaohsiung Chang Gung Memorial Hospital, Taiwan)
14:08-14:26 Lecture 5 (Presentation 15min. Q&A 3min.)Title: Skin physiology related changes associated with natural moisturising factors in the stratum corneum
Speaker: Stephen Wearne (A*STAR Skin Research Labs, Singapore)
Chair: Koh Li Fang (A*STAR Skin Research Labs, Singapore)
14:26-14:44 Lecture 6 (Presentation 15min. Q&A 3min.)Title: Molecular insight of topical emollient on the development of atopic dermatitis and atopic
march in a mice model
Speaker: Jiayi Zhang (Shanghai Jiao Tong University, China)
Chair: Li He (Kunming Medical University, China)
14:44-14:45 Closing Remarks:
Yutaka Takagi (Vice president of the 11th PAPSBARS; Josai University, Japan)
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12:05-12:50 Luncheon Special Lecture (Lecture 40min; Q&A 5min.) *sponsored by Sanofi K.K.
Skin permeability barrier formation by ceramides
Speaker: Akio Kihara (Hokkaido University, Japan)
Chair: Toshifumi Nomura (University of Tsukuba, Japan)

Skin permeability barrier formation by ceramides
Akio Kihara, PhD
Faculty of Pharmaceutical Sciences, Hokkaido University

Ceramides play an essential role in the formation of the skin permeability barrier. The stratum corneum contains a wide
variety of ceramides, as we recently reported the presence of 23 classes and 1,581 species of ceramides. Ceramides
are classified into free and protein-bound ceramides, and the free ceramides are further classified into non-acylated
ceramides and acylceramides. The stratum corneum has two structures important for the skin barrier: lipid lamellae
and corneocyte lipid envelope (CLE). Free and protein-bound ceramides are major components of lipid lamellae and
CLE, respectively. Decreased ceramide levels and altered class composition are observed in atopic dermatitis patients.
Mutations in genes involved in the synthesis of acylceramides or protein-bound ceramides cause congenital ichthyosis.
We have identified several acylceramide synthesis genes (ELOVL1, CYP4F22, PNPLA1, FATP4, and ABHD5). In thisseminar, I will describe the molecular mechanisms that produce diverse ceramides, ceramide measurement techniques,
and the physiological and pathological functions of ceramides/acylceramides.

Education:
1993 Bachelor of Science in Chemistry; Department of Science, Kyoto University
1995 Master of Science in Chemistry; Graduate School of Science, Kyoto University
1998 Ph. D. in Science; Graduate School of Science, Kyoto University

Research Experience:
1998–1999 Postdoctoral Research Fellow, Japan Society for the Promotion of Science, Kyoto University
1999–2000 Postdoctoral Research Fellow, Japan Society for the Promotion of Science, National Institute for Basic Biology, Okazaki,Japan
2001–2004 Research Associate, Graduate School of Pharmaceutical Sciences, Hokkaido University
2005–2007 Assistant Professor, Faculty of Pharmaceutical Sciences, Hokkaido University
2007–2008 Associate Professor, Faculty of Pharmaceutical Sciences, Hokkaido University
2008–present Professor, Faculty of Pharmaceutical Sciences, Hokkaido University
2021–present Dean, Faculty of Pharmaceutical Sciences, Hokkaido University10

12:53-13:11 Lecture 1 (Presentation 15min. Q&A 3min.)	Purified recombinant PNPLA1 catalyzes the synthesis of acylceramides and acylacids of the
mammalian skin barrier
Speaker: Jason M. Meyer (Tennessee Valley Healthcare System, USA)
Chair: Matthias Schmuth (Medical University Innsbruck, Austria)

Purified recombinant PNPLA1 catalyzes the synthesis ofacylceramides and acylacids of the mammalian skin barrier(Jason M. Meyer, William E. Boeglin and Alan R. Brash)
Jason M. Meyer, M.D., Ph.D.
Instructor and Attending Physician, Vanderbilt Dermatology, Tennessee Valley Healthcare System,
Nashville, TN, USA
Accumulating evidence indicates an essential role of patatin-like phospholipase domain-containing protein 1 (PNPLA1)
in the synthesis of esterified omega-hydroxy acylsphingosine (EOS) and related acylceramides and acylacids of the
mammalian skin barrier. However, little is known about the enzymatic properties of PNPLA1. We expressed and purified
a soluble, truncated form of PNPLA1 in E. coli, along with the related protein PNPLA2 (ATGL, adipose triglyceride lipase),and co-activator CGI-58. Lipid substrates were prepared as micelles or liposomes, incubated with recombinant enzymes
for 0.5 – 24 h and products were analyzed by HPLC-UV and LC-MS in comparison to authentic lipid standards. PNPLA1,
like ATGL, catalyzed lipolysis and transacylase reactions from triglyceride or diglyceride substrates. These reactions wererapid (1 – 2 h), with quantitative conversion (nmols per reaction) into free fatty acid and glyceride products. Lipolysis
products (monoacylglycerol and free fatty acid) were the most abundant species formed in the reactions with ATGLand were increased by co-incubation with CGI-58. PNPLA1 produced more of the transacylase product triacylglycerol
compared to ATGL, and triacylglycerol formation was not increased by CGI-58, in contrast to the lipolysis reaction.
PNPLA1 and ATGL also transferred acyl groups from glycerides to omega-hydroxy ceramide and omega-hydroxy
fatty acid acceptors to form EOS and acyl acid, respectively, albeit in smaller quantities (pmols per reaction). Similar
to triacylglycerol formation, EOS and acyl acid production were not stimulated by the addition of CGI-58. PNPLA1
formed EOS more efficiently than ATGL and exhibited a selectivity for the transfer of linoleate over oleate. Triacylglycerol
or diacylglycerol were effective as acyl donors, and omega-hydroxy fatty acid, omega-hydroxy ceramide or glucosyl
omega-hydroxy ceramide were effective as acceptors. These results support the hypothesis that PNPLA1 is involved in
the synthesis of EOS and other acylceramides and acylacids in epidermis via its role as a transacylase and suggest thatthe enrichment of these lipid pools with linoleic acid could result in part from the substrate selectivity of PNPLA1.

Research experience
My research is focused on the molecular basis of the skin’s permeability barrier. I completed my graduate research training inbiochemistry under the mentorship of Dr. Deneys van der Westhuyzen at the University of Kentucky, in which I helped characterize
a novel pathway of lipoprotein cholesteryl ester uptake in macrophages. After a medical internship and dermatology residency
training, I completed postdoctoral research training in the laboratories of Dr. Peter Elias and Dr. Theodora Mauro at the University ofCalifornia San Francisco. My postdoctoral research was focused on the roles of PNPLA1 and ALOX12B/12R-lipoxygenase in skinbarrier formation and helped to identify specific functions of these proteins in lamellar lipid organization and corneocyte lipid envelope
formation. I also participated in multiple collaborative studies on skin barrier formation with investigators in the United States andother countries. In 2021, I moved to Vanderbilt as a junior faculty member to collaborate with Dr. Alan Brash on the enzymatic activityof PNPLA1 and the mechanism of lipid envelope formation. This work has shed some light on the enzymatic properties of PNPLA1andgiven some clues about how PNPLA1 and other proteins contribute to skin barrier formation.

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PAPSBRS Overview

13:11-13:29 Lecture 2 (Presentation 15min. Q&A 3min.)
Antimicrobial peptides enhance skin barrier function: therapeutic implications in atopic dermatitis
Speaker: François Niyonsaba (Juntendo University, Japan)
Chair: Shin Morizane (Okayama University, Japan)

Antimicrobial peptides enhance skin barrier function: therapeutic
implications in atopic dermatitis.
François Niyonsaba, M.D., Ph.D.
Professor, Juntendo University Graduate School of Medicine

The human skin secretes a plethora of antimicrobial/host defense peptides that not only display antimicrobial activities
against invading pathogens but also exhibit various immunomodulatory functions, including the cytokine/chemokine
production and cell migration, proliferation and differentiation. They also improve angiogenesis, promote wound healing,and suppress inflammation. Among skin-derived antimicrobial peptides, human β-defensins (hBDs), cathelicidin LL37, S100A7 and antimicrobial peptide derived from insulin-like growth factor-binding protein 5 (AMP-IBP5) enhance
the function of both stratum corneum and tight junction (TJ) barriers. In addition, hBD-3 and AMP-IBP5 restore the T
helper type 2 (Th2) cytokine-mediated impairment of skin barrier function, implying a possible role of these peptides
in the pathogenesis if atopic dermatitis (AD), a skin condition characterized dysfunctional skin barrier, itching andinflammation caused by overproduction of Th2 cytokines. Indeed, both hBD-3 and AMP-IBP5 improved dermatitis-like
symptoms, suppressed inflammatory and itch-related cytokines, and improved skin barrier function in AD mice. The
ability of AMP-IBP5 to alleviate inflammation and improve skin barrier function in AD mice was abolished in mice treatedwith an antagonist of the low-density lipoprotein receptor-related protein-1 (LRP1) receptor, while inhibition of the arylhydrocarbon receptor (AhR) specific antagonist attenuated hBD-3-mediated therapeutic effects in these mice.
We observed that keratinocyte autophagy was restrained in the skin lesions of patients with AD and murine models of
AD. Interestingly, hBD-3 and LL-37 induced autophagy activation in keratinocytes through activation of AhR receptor
and P2X7 receptor, respectively. While autophagy deficiency impaired epidermal barrier and exacerbated inflammation,
administration of hBD-3 attenuated skin inflammation and enhanced the TJ barrier in AD mice through autophagy
activation. Importantly, hBD-3-mediated improvement of skin barrier function was abolished in autophagy-deficient
AD mice, suggesting a role of antimicrobial peptide-mediated autophagy in regulation of the epidermal barrier andinflammation in AD. Collectively antimicrobial peptides could be used for therapeutic purposes in the treatment of AD
through their ability to improve skin barrier function, suppress inflammation and activate keratinocyte autophagy.

Research experience:
François Niyonsaba received his MD in 1994 and Master’s degree in Orthopedics (1998) at China Medical University (China). He
joined the Department of Biochemistry at Juntendo University Graduate School of Medicine (Japan) and received his PhD in 2003.
He was appointed as Instructor (2003), Assistant Professor (2006) and Associate Professor (2007) in the Atopy (Allergy) ResearchCenter at Juntendo University. In 2010, he was assigned as Visiting Associate Professor in the Department of Microbiology and
Immunology at the University of British Columbia (Prof R.E.W. Hancock, Canada). In 2015 and 2017, he was respectively promoted
to Senior Associate Professor and Full Professor in the Faculty of International Liberal Arts, Juntendo University and became Senior
Associate Professor in January 2021 and Full Professor November 2021 in the Atopy (Allergy) Research Center. His numerous awards/
honors include the Outstanding Scholar Award, Excellent Young Researchers Overseas Visit Program from the Japan Society for the
Promotion of Science, Award for Excellence from the Eastern Asia Dermatology Congress, and Honorary Fellowship of the Asian
Academy of Dermatology and Venereology.
His research interests include “Roles of antimicrobial peptides in the skin immunity”. He has published more than 100 articles and has
more than 20 patents awarded.

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13:29-13:47 Lecture 3 (Presentation 15min. Q&A 3min.)	Topical autophagy activator enhances the epidermal permeability barrier function through SIRT1mediated ceramide synthesis
Speaker: Sekyoo Jeong (Incospharm Corp, Korea)
Chair: Haekwang Lee (P&K Skin Research Center, Korea)

Topical autophagy activator enhances the epidermal permeability
barrier function through SIRT1-mediated ceramide synthesis
Sekyoo Jeong, Ph.D.
Director and CTO, Research Team, Incospharm Corp. Daejeon, Korea. Address: #4, Kukjegwahak0-7ro, Yuseong-gu, Daejeon, South Korea (ZIP 34000) Contact information: sekyoo.jeong@gamil.com

Autophagy is an evolutionarily conserved, highly regulated cellular process for self-removal of damaged proteins
and organelles, and for the regeneration of cellular energy responding to the nutrient deprivation condition. Recently,
autophagy has emerged as a core machinery responsible for maintaining the various skin homeostasis, including
epidermal integrity, keratinocyte differentiation, senescence, melanogenesis, and sebogenesis. Previously we havereported that newly synthesized dipeptide derivative (hexacarboxymethyldipeptide-12; HMD-12) stimulated the
autophagic flux in epidermal keratinocyte and dermal fibroblast, through the binding of situin 1 (SIRT1) protein, andconsequence via deacetylation of forkhead box class O (FOXO) 1. Diversified roles of SIRT1, including stimulating
ceramide synthesis in epidermal keratinocytes, prompted us to investigate the potential effects of HMD-12 for epidermalskin barrier function. As results, HMD-12 treated keratinocytes showed increased amount of ceramides production,
mainly through the activation of ceramide synthase-2 and -3. Topical application of HDM-12 on healthy human skinfurther confirmed that relatively-long chain (C22 ~ C26) and even very-long chain (C26-C32) fatty acid-conjugatedceramides are increased in stratum corneum. Acceleration of epidermal barrier restoration after acute skin damage bytape stripping was also observed in clinical study. These results suggest that topical autophagy activator can be used forvarious skin conditions with skin barrier dysfunction, including atopic dermatitis, psoriasis, and sensitive skin.

Research Experience
Dr. Sekyoo Jeong has been working in skin research field for more than two decades, mostly in private companies. His majorarea of interest focuses on epidermal permeability barrier function, i.e., how the skin barrier is formed and, once impaired, how thecompromised barrier is restored. Sphingolipids biology for ceramides regulation, development of new formulation using ceramides
for skin barrier function, and investigation of ceramide-containing formula have been major research themes. He has been working
on identifying and evaluating new bioactive molecules for cosmetic and potential pharmaceutical application, including proteaseactivated receptor (PAR)-2 inhibitor, epidermal anti-microbial peptides (AMPs) synthesis stimulants, epidermal cannabinoid receptor
modulating molecules, and autophagy modulating compounds. He is a vice-president of Korean Society for Skin Barrier Research
and a member of Korean Society of Investigative Dermatology, Society of Cosmetic Scientists of Korea, and Japanese Investigative
Dermatology.

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13:50-14:08 Lecture 4 (Presentation 15min. Q&A 3min.)Title: Laser-mediated drug delivery to overcome the skin permeation barrier
Speaker: Jia-You Fang (Chang Gung University, Taiwan)
Chair: Chih-Hung Lee (Kaohsiung Chang Gung Memorial Hospital, Taiwan)

Laser-mediated drug delivery to overcome the skin permeation barrier
Jia-You Fang, Ph.D.
Professor. Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University,
Kweishan, Taoyuan, Taiwan

The laser modality can be used as an effective approach for enhancing drug permeation via the skin. Drug permeation
enhancement by lasers allows for more efficacious therapy than passive delivery. The treatment duration of the therapy
is possibly shortened. In addition, the applied drug dose can be lowered with less adverse effects. As compared tothe other ablation techniques, the laser is capable of controlling the etched depth by energy adjustment in a precise
way. Moreover, the skin is exposed by the laser in a non-contact fashion, minimizing the contamination or infection
risk. No bio-hazardous waste is produced after the laser application. Laser ablation even sterilizes the entrance to thecreated pores. Since the superficial ablation of SC or upper epidermis is enough to generate a significant increase inskin absorption, the fluence used for laser-assisted delivery is much lower than that used for cosmetic dermatology
or rejuvenation, assuring the safe use of the laser for drug permeation aid. The enhancement mechanisms of laserassisted drug permeation are the direct ablation of the superficial skin, optical breakdown by a photomechanical wave,
and a photothermal effect. This talk describes the development of laser-assisted drug delivery in the recent years. I will
systematically introduce the concepts and enhancement mechanisms of the technique, highlighting the potential of thelaser approach for increasing drug absorption via the skin. A recent advance of this approach is the use of fractional laser
offering limited skin damage and short recovery time. Another sign of progress regarding laser-assisted drug delivery in
the recent 5 years is the clinical trials for treating various dermatological disorders. The potential use of the laser-assisted
approach affords a novel treatment for topical drug application with significant efficacy. Although many clinical studies
have been performed, further studies using a large group for patients are needed to confirm and clarify the findings in
the in vitro or animal experiments. The laser-assisted delivery should be optimized to achieve skin targeting without therisk of diffusion into circulation.

Research experience
Over the past 25 years, Prof. Jia-You Fang and his team have made contributions to the understanding of drug delivery,
pharmaceutics, pharmacokinetics, nanomedicine, and cosmeceutics. Not only by means of providing academic research in the
Pharmaceutics Laboratory of Chang Gung University, but also by the many educational activities for the pharmaceutical, medicinal
professionals and trainees, that have expanded the knowledge and management skills that come up from their research, which isextremely translational and oriented toward industrial and clinical practice. Examples of this are the impact of low-energy ablative laser
on drug absorption enhancement, a specific technique for assisting drug permeation via skin that emerged from their work, and which
is nowadays an attractive enhancement strategy for topical administration. Another example is the passive targeting of nanoparticles
to lungs, an area where Dr. Fang and his team have made seminal contributions that have changed the view on the therapy of acutelung injury. Moreover, Dr. Fang and his group have greatly contributed to increase the availability of anti-alopecia drugs for hair follicle
targeting, by means of the design of antibody-conjugated lipid nanocarriers. His contributions add up to 310 peer-review articles,
more than 10,000 citations and H-index of 61 (Scopus).

1414:08-14:26 Lecture 5 (Presentation 15min. Q&A 3min.)
Skin physiology related changes associated with natural moisturising factors in the stratum corneum
Speaker: Stephen Wearne (A*STAR Skin Research Labs, Singapore)
Chair: Koh Li Fang (A*STAR Skin Research Labs, Singapore)

Skin physiology related changes associated with natural
moisturising factors in the stratum corneum
Stephen Wearne, PhD.
Research Fellow, A*STAR Skin Research Labs (A*SRL), A*STAR, Singapore.

Tape stripping of the skin is a non-invasive and efficient method to collect biological material, allowing for analysis of skinbarrier function and the microbiome. Until recently, analysis of the skin barrier function through metabolite measurementfrom tape strips has been a challenge due to the low biomass obtained. In this study, we developed an ultra-highperformance liquid chromatography–tandem mass spectrometry (UHPLC-MS-MS) method allowing for both relative
and absolute quantification of a targeted panel of metabolites from skin tapes. This panel includes up to 20 amino acids
and natural moisturizing factors (NMFs), including the trans and cis isomers of urocanic acid (UCA). Metabolites wereextracted with water and formic acid, before separation through an anion-exchange LC column for MS acquisition. The
simplicity and reproducibility of this method permits high-throughput analysis of samples even with very low biomass.
With this method we analysed samples from a variety of sources including a large Singapore based cohort. From thiscohort we observed differences in metabolite profile across varying skin physiological parameters, between sexes but
not ethnicity. To further assess this method, we also performed a depth analysis of healthy skin by tape stripping thestratum corneum at various depths to a maximum level of 30 tape strips. Notably, the photo exposed isomer of UCA,
cis-UCA, was found at higher levels closer to the stratum corneum surface. This protocol will be utilised to gain further
insights on the skin metabolome and probe its dynamic changes with the skin environment.

Research Experience:
I studied Molecular Cell Biology at the University of York (UK), before moving to the University of Nottingham (UK) for my Master’s
degree which focused on understanding CRISPR-Cas immunity in E.coli. I completed my PhD jointly with the University of Manchester(UK) in the lab of Prof Neil Hanley and at the Institute of Medical Biology (IMB) in A*STAR (Singapore) in Assoc. Prof Ray Dunn’s Lab,working on a novel method for the transdifferentiation based generation of pancreatic progenitor cells. Following my PhD, I worked as
the project manager for the Asian Skin Microbiome Programme (ASMP), a nascent programme focused on expanding our knowledgeof the skin microbiome in Asia. For the past year I have been working as a Research Fellow within Dr. John Common’s Lab (A*SRL)in A*STAR. There I have been working on skin barrier and skin microbiome related projects with a specific focus on utilising mass
spectrometry-based methods to better understand the metabolome of the skin.

15

of The 11th Annual Congress of Pan Asian-Pacific
Skin Barrier Research Society
PAPSBRS Overview

14:26-14:44 Lecture 6 (Presentation 15min. Q&A 3min.)Molecular insight of topical emollient on the development of atopic dermatitis and atopic march in a mice model
Speaker: Jiayi Zhang (Shanghai Jiao Tong University, China)
Chair: Li He (Kunming Medical University, China)

Molecular insight of topical emollient on the development of
atopic dermatitis and atopic march in a mice model
Jiayi Zhang, undergraduate MD
Dermatologist, Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong
University, Shanghai, China.

Atopic dermatitis (AD) is usually the initial step of the atopic march. Early intervention aimed at protecting the skin barrier
and controlling local and systemic Th2 inflammation may provide a critical opportunity to prevent infants from developing
subsequent atopic diseases. Here, we aim to investigate the effect of emollient on atopic march and its mechanism byusing a murine model of chronic atopic dermatitis (AD).
Following induction of atopic dermatitis with topical calcipotriol (MC903) and ovalbumin (OVA), one group of mice
was treated topically with a linoleic acid-ceramide-containing emollient, while mice without emollient treatment
served as controls. Additional group of normal mice served as normal controls. After 28 days, clinical, histological,
and transcriptomic analyses were performed in the skin lesions and the lung. Cytokine levels of cytokines were alsomeasured. Treatments of mice with calcipotriol and ovalbumin induced a typical phenotype of AD, accompanied byincreased expression levels of Th2 and basophil-related genes in the lung. Topical emollients markedly decreased theseverity of skin lesions and inflammatory cell infiltration. Moreover, emollient treatments significantly downregulated
expression levels of AD-related genes [286 of 1450 differentially expressed genes (DEGs)], including those related toinnate inflammation (S100a8/a9, Il1b, Defb3/6, Mmp12), chemokines (Cxcl1/3, Ccl3/4) and epidermal permeability
barrier (Krt2/6b/80, Serpinb12, Lce3e, Sprr2), etc.. Down-regulated genes were enriched in mitochondrial OXPHOSrelated pathways, while up-regulated genes were mainly enriched in axon guidance and tight junctions. Moreover, topicalemollient treatments decreased total serum levels of IgE and TSLP, along with substantial reductions in IL-4 levels.
Furthermore, 187 of 275 upregulated genes in the skin were also significantly downregulated in lung tissue, including
those involved in cytokines, cytokine/receptor interaction (Cxcl2/Cxcr2, Ccl2/3, Csf3r, etc.), and basophil activation(Mcpt8, Cd200r3, Ms4a2).
In conclusion, Topical emollient not only reduces skin inflammation, but also mitigates systemic inflammation by
decreasing TSLP and IgE levels. Moreover, topical emollient reduces chemokine production, and basophil infiltration andactivation in the lung, providing a molecular basis for blocking the atopic march.

Research experience:- MD from medical school of JiaoTong university of Shanghai (2014-2023)- master degree in Immunology and Immunopathology at University of Paris (2019-2020)- 6 months laboratory internship and 1 month course of advanced immunology in Institute of Pasteur in Pairs (2019-2020)16