tbuckley/cabot-search huggingface dataset:
CD4/CD8 Ratio and Cancer Risk Among Adults With HIV
Authors: Jessica L Castilho, Aihua Bian, Cathy A Jenkins, Bryan E Shepherd, Keith Sigel, M John Gill, Mari M Kitahata, Michael J Silverberg, Angel M Mayor, Sally B Coburn, Dorothy Wiley, Chad J Achenbach, Vincent C Marconi, Ronald J Bosch, Michael A Horberg, Charles S Rabkin, Sonia Napravnik, Richard M Novak, W Christopher Mathews, Jennifer E Thorne, Jing Sun, Keri N Althoff, Richard D Moore, Timothy R Sterling, Staci L Sudenga, Jessica L Castilho, Aihua Bian, Cathy A Jenkins, Bryan E Shepherd, Keith Sigel, M John Gill, Mari M Kitahata, Michael J Silverberg, Angel M Mayor, Sally B Coburn, Dorothy Wiley, Chad J Achenbach, Vincent C Marconi, Ronald J Bosch, Michael A Horberg, Charles S Rabkin, Sonia Napravnik, Richard M Novak, W Christopher Mathews, Jennifer E Thorne, Jing Sun, Keri N Althoff, Richard D Moore, Timothy R Sterling, Staci L Sudenga
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Independent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada. Methods We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness. Results Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P &amp;lt; .05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values. Conclusions A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.
Abstract ES6-3: Immunotherapy vs Capecitabine for Triple Negative Breast Cancer
Authors: S Loi
Journal: Cancer Research (2022)

Abstract Immunotherapy vs capecitabine for triple negative breast cancer. Educational session. Sherene Loi, MD, PhDPeter MacCallum Cancer Centre, Melbourne, Australia. Neoadjuvant treatment is now standard of care for the majority of early stage triple negative breast cancer (TNBC), with the achievement of non-pathological complete response (pCR) the main indicator to escalate treatment. Until recently only capecitabine was used in this setting. 2021 has seen reporting of the OlympiA adjuvant study, which reports major benefits for olaparib in germline BRCA positive TNBC patients, though a minority. KEYNOTE522 has now set the scene for incorporating neoadjuvant pembrolizumab with chemotherapy in early stage TNBC, with significantly improved event free survival, particularly those that do not achieve pCR. In this talk I will examine how we can rationally think about treating these patients with the available options. Citation Format: S Loi. Immunotherapy vs Capecitabine for Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES6-3.
Comparative Costs of Management Strategies for Neonates With Symptomatic Tetralogy of Fallot
Authors: Michael L O'Byrne, Andrew C Glatz, Yuan-Shung V Huang, Michael S Kelleman, Christopher J Petit, Athar M Qureshi, Shabana Shahanavaz, George T Nicholson, Shawn Batlivala, Jeffery J Meadows, Jeffrey D Zampi, Mark A Law, Jennifer C Romano, Christopher E Mascio, Paul J Chai, Shiraz Maskatia, Ivor B Asztalos, Asaad Beshish, Joelle Pettus, Amy L Pajk, Steven J Healan, Lindsay F Eilers, Taylor Merritt, Courtney E McCracken, Bryan H Goldstein
Journal: Journal of the American College of Cardiology (2022)
HSR22-130: A Retrospective Cohort Study of Selpercatinib-Treated Patients With Advanced/Metastatic Non-Small Cell Lung Cancer: Preliminary Findings From a Real-World Database in the United States
Authors: Naleen Raj Bhandari, Elizabeth Hadden, Patrick M Peterson, Ana Sofia Afonso, Scott S Barker
Journal: Journal of the National Comprehensive Cancer Network (2022)

"HSR22-130: A Retrospective Cohort Study of Selpercatinib-Treated Patients With Advanced/Metastatic Non-Small Cell Lung Cancer: Preliminary Findings From a Real-World Database in the United States" published on 31 Mar 2022 by National Comprehensive Cancer Network.
<i>Listeria</i> delivers tetanus toxoid protein to pancreatic tumors and induces cancer cell death in mice
Authors: Benson Chellakkan Selvanesan, Dinesh Chandra, Wilber Quispe-Tintaya, Arthee Jahangir, Ankur Patel, Kiran Meena, Rodrigo Alberto Alves Da Silva, Madeline Friedman, Lisa Gabor, Olivia Khouri, Steven K. Libutti, Ziqiang Yuan, Jenny Li, Sarah Siddiqui, Amanda Beck, Lydia Tesfa, Wade Koba, Jennifer Chuy, John C. McAuliffe, Rojin Jafari, David Entenberg, Yarong Wang, John Condeelis, Vera DesMarais, Vinod Balachandran, Xusheng Zhang, Ken Lin, Claudia Gravekamp
Journal: Science Translational Medicine (2022)

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease. Tumors are poorly immunogenic and immunosuppressive, preventing T cell activation in the tumor microenvironment. Here, we present a microbial-based immunotherapeutic treatment for selective delivery of an immunogenic tetanus toxoid protein (TT 856-1313 ) into PDAC tumor cells by attenuated Listeria monocytogenes . This treatment reactivated preexisting TT-specific memory T cells to kill infected tumor cells in mice. Treatment of KrasG12D,p53R172H, Pdx1-Cre (KPC) mice with Listeria -TT resulted in TT accumulation inside tumor cells, attraction of TT-specific memory CD4 T cells to the tumor microenvironment, and production of perforin and granzyme B in tumors. Low doses of gemcitabine (GEM) increased immune effects of Listeria -TT, turning immunologically cold into hot tumors in mice. In vivo depletion of T cells from Listeria -TT + GEM–treated mice demonstrated a CD4 T cell–mediated reduction in tumor burden. CD4 T cells from TT-vaccinated mice were able to kill TT-expressing Panc-02 tumor cells in vitro. In addition, peritumoral lymph node–like structures were observed in close contact with pancreatic tumors in KPC mice treated with Listeria -TT or Listeria -TT + GEM. These structures displayed CD4 and CD8 T cells producing perforin and granzyme B. Whereas CD4 T cells efficiently infiltrated the KPC tumors, CD8 T cells did not. Listeria -TT + GEM treatment of KPC mice with advanced PDAC reduced tumor burden by 80% and metastases by 87% after treatment and increased survival by 40% compared to nontreated mice. These results suggest that Listeria -delivered recall antigens could be an alternative to neoantigen-mediated cancer immunotherapy.
Anatomy promotes neutral coexistence of strains in the human skin microbiome
Authors: Arolyn Conwill, Anne C. Kuan, Ravalika Damerla, Alexandra J. Poret, Jacob S. Baker, A. Delphine Tripp, Eric J. Alm, Tami D. Lieberman
Journal: Cell Host & Microbe (2022)

What enables strains of the same species to coexist in a microbiome? Here, we investigate whether host anatomy can explain strain co-residence of Cutibacterium acnes, the most abundant species on human skin. We reconstruct on-person evolution and migration using whole-genome sequencing of C. acnes colonies acquired from healthy subjects, including from individual skin pores, and find considerable spatial structure at the level of pores. Although lineages (sets of colonies separated by <100 mutations) with in vitro fitness differences coexist within centimeter-scale regions, each pore is dominated by a single lineage. Moreover, colonies from a pore typically have identical genomes. An absence of adaptive signatures suggests a genotype-independent source of low within-pore diversity. We therefore propose that pore anatomy imposes random single-cell bottlenecks; the resulting population fragmentation reduces competition and promotes coexistence. Our findings suggest that therapeutic interventions involving pore-dwelling species might focus on removing resident populations over optimizing probiotic fitness.
DIFFERENTIAL INTERACTIONS BETWEEN FUNCTIONAL MITRAL REGURGITATION AND MYOCARDIAL SCAR OR REMODELING IN ISCHEMIC VERSUS NON-ISCHEMIC CARDIOMYOPATHY: A CARDIAC MAGNETIC RESONANCE STUDY
Authors: Tom Kai Ming Wang, Duygu Kocyigit, Nicholas Chan, Chris Anthony, Jennifer Bullen, Zoran Popovic, Wai Hong Wilson Tang, Brian P. Griffin, Scott D. Flamm, Deborah Kwon
Journal: Journal of the American College of Cardiology (2022)
DERIVATION AND VALIDATION OF A RISK STRATIFICATION TOOL IN PATIENTS WITH TYPE 2 MYOCARDIAL INFARCTION
Authors: Caelan Taggart, Karla Monterrubio-Gomez, Andreas Roos, Erik Kadesjo, Dorothea Kimenai, Anda Bularga, Ryan Wereski, Martin Holzmann, Nicholas L. Mills, Catalina Vallejos, Andrew R. Chapman
Journal: Journal of the American College of Cardiology (2022)
Operative Autonomy of Surgical Residents and Patient Outcomes—Reply
Authors: Joseph B. Oliver, Anastasia Kunac, Devashish J. Anjaria
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Why Some Individuals With Tourette Syndrome Experience Assault and Perpetrate Criminal Behavior
Authors: Davide Martino, James F. Leckman, Michael S. Okun
Journal: JAMA Neurology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Reply
Authors: Vladimir V. Loukachov, Karel A. van Dort, Robin Erken, Henk W. Reesink, Neeltje A. Kootstra
Journal: Hepatology (2022)

Abbreviation ORF open reading frame We thank Dr. Rydell and colleagues for their interest in our manuscript and the possible technical explanation for the absence of integrated HBV DNA containing open reading frame (ORF) C in the livers of patients with chronic hepatitis B (CHB) found in our study. We agree that HBV integrants may start at nucleotide 1820 or further, because a previous study showed that these breaking points occurred in a much wider region. Dr. Rydell pointed out that this could possibly implicate that the absence of ORF C‐containing HBV integrants in our study is explained by our primer choice. For the Alu‐qPCR, the primers were designed to bind to sequences closest to the HBV integrants' breaking point, because this assured amplification of the shortest possible amplicon. In the region downstream of the current primer, high variability was seen between different HBV genotypes limiting this region for primer design. As one primer set was desirable to detect all possible HBV genotypes, the current primer set was selected for the Alu‐PCR. Consequently, our Alu‐PCR will not detect integrants with a more downstream breaking point. However, Svicher et al. showed that around 65% of the HBV integrations occurred between HBV nucleotide positions 1590 and 1840, which corresponds to the region in‐between direct repeat 1 and 2.[1] Therefore, we believe that at least a fraction of HBV integrants containing ORF C should have been detected using our ORF C primer set. As pointed out by Dr. Rydell and colleagues, our results were in line with other studies that found limited to no HBV integrants containing ORF C in patients with CHB.[2–4] CONFLICT OF INTEREST Nothing to report.
Canalization of the Polygenic Risk for Common Diseases and Traits in the UK Biobank Cohort
Authors: Sini Nagpal, Raghav Tandon, Greg Gibson
Journal: Molecular Biology and Evolution (2022)

Since organisms develop and thrive in the face of constant perturbations due to environmental and genetic variation, species may evolve resilient genetic architectures. We sought evidence for this process, known as canalization, through a comparison of the prevalence of phenotypes as a function of the polygenic score (PGS) across environments in the UK Biobank cohort study. Contrasting seven diseases and three categorical phenotypes with respect to 151 exposures in 408,925 people, the deviation between the prevalence-risk curves was observed to increase monotonically with the PGS percentile in one-fifth of the comparisons, suggesting extensive PGS-by-Environment (PGS×E) interaction. After adjustment for the dependency of allelic effect sizes on increased prevalence in the perturbing environment, cases where polygenic influences are greater or lesser than expected are seen to be particularly pervasive for educational attainment, obesity, and metabolic condition type-2 diabetes. Inflammatory bowel disease analysis shows fewer interactions but confirms that smoking and some aspects of diet influence risk. Notably, body mass index has more evidence for decanalization (increased genetic influence at the extremes of polygenic risk), whereas the waist-to-hip ratio shows canalization, reflecting different evolutionary pressures on the architectures of these weight-related traits. An additional 10 % of comparisons showed evidence for an additive shift of prevalence independent of PGS between exposures. These results provide the first widespread evidence for canalization protecting against disease in humans and have implications for personalized medicine as well as understanding the evolution of complex traits. The findings can be explored through an R shiny app at https://canalization-gibsonlab.shinyapps.io/rshiny/.
PALMITOYLETHANOLAMIDE-POLYDATIN COMPLEX REDUCES INFLAMMATION IN HUMAN VASCULAR ENDOTHELIAL CELLS EXPOSED SEQUENTIALLY TO DOXORUBICIN AND TRASTUZUMAB THROUGH LKB1-AMPK AND NLRP3-CYTOKINE RELATED PATHWAYS
Authors: Nicola Maurea, Martina Iovine, Simona Buccolo, Carlo Maurea, Andrea Paccone, Vincenzo Quagliariello
Journal: Journal of the American College of Cardiology (2022)
IS A FAMILY HISTORY OF CORONARY HEART DISEASE AN INDEPENDENT CARDIOVASCULAR RISK FACTOR?
Authors: Stefan Simovic, Goran Davidovic, Jinsung Yoon, Sasko Kedev, Marija Zdravkovic, Zorana Vasiljevic, Davor Milicic, Olivia Manfrini, Mihaela van der Schaar, Chris P. Gale, Maria Bergami, Lina Badimon, Edina Cenko, Raffaele Bugiardini
Journal: Journal of the American College of Cardiology (2022)
IPO11 regulates the nuclear import of BZW1/2 and is necessary for AML cells and stem cells
Authors: Boaz Nachmias, Dilshad H. Khan, Veronique Voisin, Arvind S. Mer, Geethu Emily Thomas, Nadav Segev, Jonathan St-Germain, Rose Hurren, Marcela Gronda, Aaron Botham, Xiaoming Wang, Neil Maclean, Ayesh K. Seneviratne, Nathan Duong, Changjiang Xu, Andrea Arruda, Elias Orouji, Arash Algouneh, Razqallah Hakem, Liran Shlush, Mark D. Minden, Brian Raught, Gary D. Bader, Aaron D. Schimmer
Journal: Leukemia (2022)

AML cells are arranged in a hierarchy with stem/progenitor cells giving rise to more differentiated bulk cells. Despite the importance of stem/progenitors in the pathogenesis of AML, the determinants of the AML stem/progenitor state are not fully understood. Through a comparison of genes that are significant for growth and viability of AML cells by way of a CRISPR screen, with genes that are differentially expressed in leukemia stem cells (LSC), we identified importin 11 (IPO11) as a novel target in AML. Importin 11 (IPO11) is a member of the importin β family of proteins that mediate transport of proteins across the nuclear membrane. In AML, knockdown of IPO11 decreased growth, reduced engraftment potential of LSC, and induced differentiation. Mechanistically, we identified the transcription factors BZW1 and BZW2 as novel cargo of IPO11. We further show that BZW1/2 mediate a transcriptional signature that promotes stemness and survival of LSC. Thus, we demonstrate for the first time how specific cytoplasmic-nuclear regulation supports stem-like transcriptional signature in relapsed AML.
Novel imaging biomarkers predict outcomes in stage III unresectable non-small cell lung cancer treated with chemoradiation and durvalumab
Authors: Khalid Jazieh, Mohammadhadi Khorrami, Anas Saad, Mohamed Gad, Amit Gupta, Pradnya Patil, Vidya Sankar Viswanathan, Prabhakar Rajiah, Charles J Nock, Michael Gilkey, Pingfu Fu, Nathan A Pennell, Anant Madabhushi
Journal: Journal for ImmunoTherapy of Cancer (2022)

The landmark study of durvalumab as consolidation therapy in NSCLC patients (PACIFIC trial) demonstrated significantly longer progression-free survival (PFS) in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) treated with durvalumab (immunotherapy, IO) therapy after chemoradiotherapy (CRT). In clinical practice in the USA, durvalumab continues to be used in patients across all levels of programmed cell death ligand-1 (PD-L1) expression. While immune therapies have shown promise in several cancers, some patients either do not respond to the therapy or have cancer recurrence after an initial response. It is not clear so far who will benefit of this therapy or what the mechanisms behind treatment failure are.
Kissing in the Airway: Collateral Damage from Tracheobronchomalacia
Authors: Aravind A. Menon, Majid Shafiq
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Kissing in the Airway: Collateral Damage from Tracheobronchomalacia." American Journal of Respiratory and Critical Care Medicine, 205(4), pp. e8–e9
The spatial self-organization within pluripotent stem cell colonies is continued in detaching aggregates
Authors: Mohamed H. Elsafi Mabrouk, Roman Goetzke, Giulio Abagnale, Burcu Yesilyurt, Lucia Salz, Olivia Cypris, Philipp Glück, Sven Liesenfelder, Kira Zeevaert, Zhiyao Ma, Marcelo A.S. Toledo, Ronghui Li, Ivan G. Costa, Angelika Lampert, Vivek Pachauri, Uwe Schnakenberg, Martin Zenke, Wolfgang Wagner
Journal: Biomaterials (2022)

Colonies of induced pluripotent stem cells (iPSCs) reveal aspects of self-organization even under culture conditions that maintain pluripotency. To investigate the dynamics of this process under spatial confinement, we used either polydimethylsiloxane (PDMS) pillars or micro-contact printing of vitronectin. There was a progressive upregulation of OCT4, E-cadherin, and NANOG within 70 μm from the outer rim of iPSC colonies. Single-cell RNA-sequencing and spatial reconstruction of gene expression demonstrated that OCT4high subsets, residing at the edge of the colony, have pronounced up-regulation of the TGF-β pathway, particularly of NODAL and its inhibitor LEFTY. Interestingly, after 5-7 days, iPSC colonies detached spontaneously from micro-contact printed substrates to form 3D aggregates. This new method allowed generation of embryoid bodies (EBs) of controlled size without enzymatic or mechanical treatment. Within the early 3D aggregates, radial organization and differential gene expression continued in analogy to the changes observed during self-organization of iPSC colonies. Early self-detached aggregates revealed up-regulated germline-specific gene expression patterns as compared to conventional EBs. However, there were no marked differences after further directed differentiation toward hematopoietic, mesenchymal, and neuronal lineages. Our results provide further insight into the gradual self-organization within iPSC colonies and at their transition into EBs.
NUAK1 promotes organ fibrosis via YAP and TGF-β/SMAD signaling
Authors: Tianzhou Zhang, Xiaolin He, Lauren Caldwell, Santosh Kumar Goru, Luisa Ulloa Severino, Monica F. Tolosa, Paraish S. Misra, Caitríona M. McEvoy, Tania Christova, Yong Liu, Cassandra Atin, Johnny Zhang, Catherine Hu, Noah Vukosa, Xiaolan Chen, Adriana Krizova, Anish Kirpalani, Alex Gregorieff, Ruoyu Ni, Kin Chan, Mandeep K. Gill, Liliana Attisano, Jeffrey L. Wrana, Darren A. Yuen
Journal: Science Translational Medicine (2022)

Fibrosis is a central pathway that drives progression of multiple chronic diseases, yet few safe and effective clinical antifibrotic therapies exist. In most fibrotic disorders, transforming growth factor–β (TGF-β)–driven scarring is an important pathologic feature and a key contributor to disease progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are two closely related transcription cofactors that are important for coordinating fibrogenesis after organ injury, but how they are activated in response to tissue injury has, so far, remained unclear. Here, we describe NUAK family kinase 1 (NUAK1) as a TGF-β–inducible profibrotic kinase that is up-regulated in multiple fibrotic organs in mice and humans. Mechanistically, we show that TGF-β induces a rapid increase in NUAK1 in fibroblasts. NUAK1, in turn, can promote profibrotic YAP and TGF-β/SMAD signaling, ultimately leading to organ scarring. Moreover, activated YAP and TAZ can induce further NUAK1 expression, creating a profibrotic positive feedback loop that enables persistent fibrosis. Using mouse models of kidney, lung, and liver fibrosis, we demonstrate that this fibrogenic signaling loop can be interrupted via fibroblast-specific loss of NUAK1 expression, leading to marked attenuation of fibrosis. Pharmacologic NUAK1 inhibition also reduced scarring, either when initiated immediately after injury or when initiated after fibrosis was already established. Together, our data suggest that NUAK1 plays a critical, previously unrecognized role in fibrogenesis and represents an attractive target for strategies that aim to slow fibrotic disease progression.