DIVISIONOFDIGESTIVEANDLIVERDISEASES

Research Summaries

RESEARCH FACULTY BASIC/LABORATORY BASED RESEARCH

Timothy C. Wang MD Silberberg Professor of Medicine Chief, Division of Digestive and Liver Diseases

My laboratory has for decades investigated the molecular mechanisms of gastrointestinal carcinogenesis, continuously funded by the NIH for 30 years and by the NCI for 15 years, currently funded by an NCI R35 Outstanding Investigator Award. My lab has worked for many years on the role of inflammation in modulating stem cells and promoting gastrointestinal neoplasia using mouse models. I have defined key roles for stromal cells in tumor development, including myeloid cells, ILCs and nerves. Our lab makes extensive use of transgenic/ knockout mice, stem cells, lineage tracing, 3D organoids, scRNA-seq and FACS analysis of immune/epithelial cells in the gut. I am also GI Division Chief at Columbia, and Director of the GI/Pancreas Cancer Program

and Tumor Biology and Microenvironment (TBM) program in the Herbert Irving Cancer Center. I served for over a decade as director of the Columbia NCI U54 Tumor Microenvironment (TMEN) program, and I currently direct the Barrett’s Esophageal Translational Research Network (BETRNet) program and the NIDDK UO1 Intestinal Stem Cell Consortium (ISCC) at Columbia. I am Past President of the American Gastroenterology Association (AGA), and recipient of the William Beaumont Award. Over the past decade, my laboratory has increasingly focused on pancreatic cancer with several high-profile publications. Our lab has published frequently in high impact journals including Cell Stem Cell, Cancer Cell, Cell, Science, Nature, and Gastroenterology. I am the Research Director for the Pancreas Center; and have brought together basic and clinical investigators into a cohesive, translational program. I enjoy mentoring fellows and postdocs, having trained many on T32 and K grants. Our lab collaborates extensively with more than a dozen investigators at CUMC, and many others worldwide. Select Publications: Chang W, Wang H, Kim W, Liu Y, Deng H, Liu H, Jiang Z, Niu Z, Sheng W, Nápoles OC, Sun Y, Xu J, Sepulveda A, Hayakawa Y, Bass AJ, Wang TC. Hormonal suppression of stem cells inhibits symmetric cell division and gastric tumorigenesis. Cell Stem Cell. 2020 Feb 20. pii: S1934-5909(20)30020-5. doi: 10.1016/j.stem.2020.01.020. [Epub ahead of print] PMID: 32142681

Renz BW, Takahashi R, Tanaka T, Macchini M, Hayakawa Y, Dantes Z, Maurer HC, Chen X, Jiang Z, Westphalen CB, Ilmer M, Valenti G, Mohanta SK, Habenicht AJR, Middelhoff M, Chu T, Nagar K, Tailor Y, Casadei R, Di Marco M, Kleespies A, Friedman RA, Remotti H, Reichert M, Worthley DL, Neumann J, Werner J, Iuga AC, Olive KP, Wang TC. B2 adrenergic-neurotrophin feedforward loop promotes pancreatic cancer. Cancer Cell. 2018; 33(1):75-90.e7. doi: 10.1016/j.ccell.2017.11.007. PMID:29249692

Worthley DL, Churchill M, Compton JT, Tailor Y, Rao M, Si Y, Levin D, Schwartz MG, Uygur A, Hayakawa Y, Gross S, Renz BW, Setlik W, Martinez AN, Chen X, Nizami S, Lee HG, Kang HP, Caldwell JM, Asfaha S, Westphalen CB, Graham T, Jin G, Nagar K, Wang H, Kheirbek MA, Kolhe A, Carpenter J, Glaire M, Nair A, Renders S, Manieri N, Muthupalani S, Fox JG, Reichert M, Giraud AS, Schwabe RF, Pradere JP, Walton K, Prakash A, Gumucio D, Rustgi AK, Stappenbeck TS, Friedman RA, Gershon MD, Sims P, Grikscheit T, Lee FY, Karsenty G, Mukherjee S, Wang TC. Gremlin1 identifies a skeletal cell with bone, cartilage, and reticular stromal potential. Cell. 2015; 160(1-2):269-84. doi: 10.1016/j.cell.2014.11.042. PMID:5594183 Joel Gabre MD Instructor of Medicine

I use novel 3D organoid cultures to study esophageal development and esophageal adenocarcinoma. I first became interested in the molecular basis of gastrointestinal malignancies as a resident physician in the lab of Yana Zavros, PhD at the University of Cincinnati where I learned advanced 3D cell culture techniques to model gastric metaplasia and gastric carcinogenesis. I also introduced and helped develop a protocol to use patient-derived 3D gastric cancer organoids for personalized medicine. Given this interest and experience in metaplasia and 3D organoid cultures, I joined the lab of Dr. Anil K. Rustgi, Director of the Herbert Irving Comprehensive Cancer Center (HICCC) at Columbia University. I have focused on using 3D esophageal organoids to study mechanisms of cellular plasticity

and trans-differentiation. In particular, I seek to understand conserved developmental pathways re-activated during metaplasia using human induced pluripotent stem cell (iPSC) derived esophageal organoids. I have also continued to use patient-derived organoids from patients with esophageal adenocarcinoma for personalized medicine. I have been recruited to join Dr. Rustgi as an Instructor of Medicine in the Division of Digestive and Liver Diseases at Columbia while I

continue as a trainee in his laboratory. The unique opportunities for collaboration with investigators in related domains of esophageal epithelial biology at Columbia make it an ideal environment for my interests in metaplasia and 3D organoid cultures for personalized medicine. Select Publications: Mukhopadhyay S, Gabre J, Chabasse C, Bromberg JS, Antalis TM, Sarkar R. Int J Mol Sci 2020 21(5). pii: E1650. doi: 10.3390/ijms21051650. PMID: 32121269

Bertaux-Skeirik N, Wunderlich M, Teal E, Chakrabarti J, Biesiada J, Mahe M, Sundaram N, Gabre J, Hawkins J, Jian G, Engevik AC, Yang L, Wang J, Goldenring JR, Qualls JE, Medvedovic M, Helmrath MA, Diwan T, Mulloy JC, Zavros Y. CD44 variant isoform 9 emerges in response to injury and contributes to the regeneration of the gastric epithelium. J Pathol. 2017 Aug;242(4):463-475. doi: 10.1002/path.4918. PMID: 28497484

Bertaux-Skeirik N, Centeno J, Gao J, Gabre J, Zavros Y. Oncogenic transformation of human-derived gastric organoids. Methods Mol Biol. 2019; 1576:205-213. doi: 10.1007/7651_2016_4. PMID: 27539460 Arnold S. Han MD PhD Loeb Assistant Professor of Medicine and Microbiology and Immunology

I am trained as a clinical gastroenterologist and a basic scientist with expertise in immunology. I am applying my very unique training as both a basic scientist trained in immunology and a clinician trained in Internal Medicine and Gastroenterology to pursue clinically important scientific questions in tumor immunity and autoimmunity. My team investigates the function of T cells as they pertain to human diseases. We have developed and are actively developing technologies that enable the study of T cell function and specificity at a single-cell level. We are applying this analysis to the study of T cells in cancer and autoimmune diseases. Our approach enables the extensive study of T cell function

and also the ability to recapitulate TCRs for functional studies and therapeutic application. Select publications: Li Y, Teteloshvili N, Tan S, Rao S, Han A, Yang YG, Creusot RJ. Humanized Mice Reveal New Insights Into the Thymic Selection of Human Autoreactive CD8+ T Cells. Front Immunol 2019 10:63doi: 10.3389/fimmu.2019.00063. PMID: 30778347

Gee MH*, Han A*, Lofgren SM, Beausang JF, Mendoza JL, Birnbaum ME, Bethune MT, Fischer S, Yang X, Gomez-Eerland R, Bingham DB, Sibener LV, Fernandes RA, Velasco A, Baltimore D, Schumacher TN, Khatri P, Quake SR, Davis MM, Garcia KC. Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes. Cell 2018; 172(3):549-563. PMID: 29275860 *equal contribution

Glanville J, Huang H, Nau A, Hatton O, Wagar LE, Rubelt F, Ji X, Han A, Krams SM, Pettus C, Haas N, Arlehamn CSL, Sette A, Boyd SD, Scriba TJ, Martinez OM, Davis MM. Identifying specificity groups in the T cell receptor repertoire. Nature 2017; 547(7661):94-98. PMID: 28636589

Hiroshi Nakagawa MD PhD Associate Professor of Medicine

I have a broad background in gastrointestinal epithelial biology, tumor biology, and molecular and cellular biology with specific training and expertise in key research areas. As a postdoctoral fellow at the Massachusetts General Hospital (1993-1996), I investigated cell-cycle regulation via cyclin D1 and the transcriptional regulation of genes in the esophageal squamous epithelium; and developed the first transgenic mouse model of esophageal squamous cell carcinoma (ESCC). At Penn GI Division (1998-2019), I expanded my research to study EGFR, Notch and other molecules essential

in ESCC intra-tumoral cancer cell heterogeneity (e.g. CD44) and environmental risk factors (e.g. alcohol) for esophageal carcinogenesis. As Associate Director of the Penn Cell Culture/iPS Core, I provided expertise in all aspects of isolation of primary mouse and human esophageal cells, establishing cell lines, genetic modifications of esophageal cells via viral vectors (e.g. Tetracycline-inducible retroviral/lentiviral vectors, RNA interference, and the CRISPR/Cas9 system) and physiologically relevant three-dimensional (3D) culture systems (3D organotypic culture and 3D organoids, the latter translatable in personalized medicine). I pioneered the recapitulation of a variety of esophageal disease conditions in patient-derived 3D organoids grown ex vivo and have authored articles and given talks in various national and international meetings, on esophageal 3D culture systems. I have a demonstrated record of successful and productive research projects in esophageal epithelial biology, tumor biology and common clinical diseases (e.g. eosinophilic esophagitis, Barrett’s esophagus, and esophageal cancers). Joining the Herbert Irving Comprehensive Cancer Center and the Division of Digestive and Liver Diseases at Columbia University (July, 2019-), I continue research on fundamental mechanisms in epithelial renewal, differentiation, and cell fate determination with the above esophageal diseases as well as cancers of the adjacent oropharyngeal mucosa (head-and neck) as unique model systems.

Select Publications: Kasagi Y, Chandramouleeswaran PM, Whelan KA, Tanaka K, Giroux V, Sharma M, Wang J, Benitez AJ, DeMarshall M, Tobias JW, Hamilton KE, Falk GW, Spergel JM, Klein-Szanto AJ, Rustgi AK, Muir AB, Nakagawa H. The Esophageal Organoid System Reveals Functional Interplay Between Notch and Cytokines in Reactive Epithelial Changes. Cell Mol Gastroenterol Hepatol. 2018; 5(3):333-352 PMID: 29552622

Whelan KA, Chandramouleeswaran PM, Tanaka K, Natsuizaka M, Guha M, Srinivasan S, Darling DS, Kita Y, Natsugoe S, Winkler JD, Klein-Szanto AJ, Amaravadi RK, Avadhani NG, Rustgi AK, Nakagawa H. Autophagy supports generation of cells with high CD44 expression via modulation of oxidative stress and Parkin-mediated mitochondrial clearance. Oncogene. 2017 Aug 24;36(34):4843-4858. PMID: 28414310 Natsuizaka M, Whelan KA, Kagawa S, Tanaka K, Giroux V, Chandramouleeswaran PM, Long A, Sahu V, Darling DS, Que J, Yang Y, Katz JP, Wileyto EP, Basu D, Kita Y, Natsugoe S, Naganuma S, Klein-Szanto AJ, Diehl JA, Bass AJ, Wong KK, Rustgi AK, Nakagawa H. Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma. Nat Commun. 2017; 8(1):1758. PMID: 29170450 Kenneth P. Olive PhD Associate Professor of Medicine

I lead a multidisciplinary team of scientists and physicians at all levels of training who are devoted to the study of pancreatic cancer. We utilize human samples, advanced mouse models, tumor explant cultures, and computational techniques to identify and target critical tumor-specific vulnerabilities of pancreatic cancer. Specific research areas include: cancer metabolism, tumor-stroma-immune crosstalk, precision medicine, tumor-microbial interactions, and imaging. We develop questions in these areas with support from advanced systems biology techniques based on regulatory network analysis, and test our ideas using a suite of innovative translational approaches. In particular, our “Mouse Hospital” is a multidisciplinary infrastructure that integrates

small animal imaging, surgery, radiology, treatment, pathology, pharmacology, molecular biology, and tissue sampling to enable the detailed interrogation of cancer phenotypes in vivo. Complementing my laboratory research, I have also built a large-scale translational core facility called the Oncology Precision Therapeutics and Imaging Core (OPTIC). This NCI designated shared resource provides both small animal imaging technology as well as a comprehensive translational therapeutics service to CUMC. Select Publications: Badgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee H-J, Purohit V, Sagalovskiy IR, Ma A, Kapilian J, Firl CEM, Decker AR, Sastra SA, Palermo CF, Andrade LR, Sajjakulnukit P, Zhang L, Tolstyka ZP, Hirschhorn T, Lamb C, Liu T, Gu W, Seeley ES, Stone E, Georgiou G, Manor U, Iuga A, Wahl GM, Stockwell BR, Lyssiotis CA, Olive KP. Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science. 2020; 368(6486)85-89. PMID:32241947

Eberle-Singh JA, Sagalovskiy I, Maurer HC, Sastra SA, Palermo CF, Decker AR, Kim MJ, Sheedy J, Mollin A, Cao L, Hu J, Branstrom A, Weetall M, Olive KP. “Effective delivery of a microtubule polymerization inhibitor synergizes with standard regimens in models of pancreatic ductal adenocarcinoma”. Clinical Cancer Research. 2019; 25(18):5548-5560. PMID: 31175095

Maurer C, Holmstrom SR, He J, Laise P, Su T, Ahmed A, Hibshoosh H, Chabot JA, Oberstein PE, Sepulveda AR, Genkinger JM, Zhang J, Iuga AC, Bansal M, Califano A, Olive KP. Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes. Gut. 2019; 68(6):1034-1043. PMID: 30658994 Jianwen Que, MD, PhD Associate Professor of Medicine

I am an Associate Professor of Medicine at Columbia University. My research is focused on the role of stem/progenitor cells in homeostasis and disease pathogenesis in gastrointestinal organs including esophagus, stomach etc. I have made several different knockin overexpression and knockout mouse lines, so my lab has expertise in mouse genetic modeling and in the isolation, immunostaining of cells and tissues, and related techniques. We also have major expertise in the areas of stem cell differentiation, isolation and culture of stem cells, stem cell/microenvironment interaction in the initiation and progression of esophageal diseases including eosinophilic esophagitis and Barret’s esophagus. Part of our findings were published in journals including

Nature, Cell Stem Cell, Developmental Cell and Journal of Clinical Investigation. My training in clinical medicine has helped shape my research direction, that is, to model and find cures for clinical diseases. The long-term interests in my laboratory are focused on understanding the molecular processes that collectively serve to regulate the morphogenesis and maintenance of two foregut-derived organs, the lung and esophagus. Currently, we focus on three diseases, Eosinophilic esophagitis, Barrett’s esophagus and lung fibrosis. Select Publications: Kim E, Jiang M, Huang H, Zhang Y, Tjota N, Gao X, Robert J, Gilmore N, Gan L, Que J. Isl1 Regulation of Nkx2.1 in the Early Foregut Epithelium Is Required for Trachea-Esophageal Separation and Lung Lobation. Dev Cell. 2019; 51(6):675-683. PMID: 31813798

Zhang Y, Yang Y, Jiang M, Huang SX, Zhang W, Al Alam D, Danopoulos S, Mori M, Chen YW, Balasubramanian R, Chuva de Sousa Lopes SM, Serra C, Bialecka M, Kim E, Lin S, Toste de Carvalho ALR, Riccio PN, Cardoso WV, Zhang X, Snoeck HW, Que J. 3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling. Cell Stem Cell. 2018 Oct 4;23(4):516-529 PMID: 30244870

Jiang M, Li H, Zhang Y, Yang Y, Lu R, Liu K, Lin S, Lan X, Wang H, Wu H, Zhu J, Zhou Z, Xu J, Lee DK, Zhang L, Lee YC, Yuan J, Abrams JA, Wang TC, Sepulveda AR, Wu Q, Chen H, Sun X, She J, Chen X, Que J. Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus. Nature. 2017; 550(7677):529-533. PMID: 29019984 Robert F. Schwabe MD Associate Professor of Medicine

My research seeks to elucidate mechanisms by which fibrosis and cancer develop in the chronically injured liver using mouse models, patient samples as well as novel Systems Biology approaches. To understand the contribution of liver fibroblasts and the underlying pathways, my lab has generated hepatic stellate cell-selective Cre transgenic mouse (LratCre), allowing to trace and functionally manipulate hepatic stellate cell (HSC)-derived fibroblasts. Current efforts are to delineate the contribution of HSC to different types of injury and fibrosis, including non-alcoholic steatohepatitis (NASH), with the ultimate goal to identify novel druggable pathways that promote HSC activation and liver fibrosis. Besides fibrosis, my lab also investigates liver cancer development. Liver cancer is the

second leading cause of cancer mortality world- wide, and almost never develops in healthy livers. In most patients, liver cancer develops after decades of chronic liver injury, inflammation and fibrosis, supporting the notion that liver cancer is “a wound that does not heal”. One interest of my laboratory is to unravel the relationship between fibrosis and cancer development. Using mouse models, we try to understand whether fibroblasts and ECM promote the development of hepatocellular carcinoma (HCC) using LratCre mice to ablate or functionally manipulate cancer-associated fibroblasts (CAF) in liver carcinogenesis. In addition, my laboratory is interested in the role of fibrosis and CAF in the development of cholangiocarcinoma (CCA). Using above-described tools such as LratCre-transgenic mice, we seek to uncover how the absence or inactivation of stellate cell-derived CAF and ECM proteins affects CCA development. Key data are confirmed using bulk and single cell RNA-sequencing as well as novel Systems Biology approaches in patient samples. Finally, my lab seeks to uncover druggable "master regulators" in HCC and CCA using novel Systems Biology approaches in collaboration with the Califano lab. Select Publications: Schwabe RF, Tabas I, Pajvani UB. Mechanisms of fibrosis development in nonalcoholic steatohepatitis. Gastroenterology 2020 May: 158(7):1913-1928. PMID: 32044315

Mederacke I, Hsu CC, Troeger JS, Huebener P, Mu X, Dapito DH, Pradere JP, Schwabe RF. Fate tracing reveals hepatic stellate cells as dominant contributors of liver fibrosis independent of its aetiology. Nature Commun. 2013; 4:2823. Doi: 10. 1038/ncomms3823. PMID: 24264436

Dapito DH, Mencin A, Gwak GY, Pradere JP, Jang MK, Mederacke I, Caviglia JM, Khiabanian H, Adeyemi A, Bataller R, Lefkowitch JH, Bower M, Friedman R, Sartor RB, Rabadan R, Schwabe RF. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 2012 Apr 17:21(4):504-16. PMID: 22516259 Howard J. Worman MD Professor of Medicine, Pathology and Cell Biology

I trained in cell biology and as an internist. My major research focus has been on the nuclear lamina and nuclear envelope. In 1993, my group characterized LMNA, the gene encoding the A-type nuclear lamins, mutations in which cause a broad range of diseases often called laminopathies. These include cardiomyopathy, muscular dystrophy, Hutchinson-Gilford progeria syndrome and Dunnigan-type familial partial lipodystrophy. These discoveries have led to my developing expertise in molecular genetics and genomic medicine, including mutation calling from human genome sequences and phenotype-genotype analyses in humans with inherited diseases. I have also generated and used

numerous mouse models of human disease to dissect pathogenic mechanisms. In addition to extensive research using mouse models of diseases caused by LMNA mutations, my laboratory has performed genome-wide association studies in mice to identify genes that influence liver phenotypes. We have also generated novel models of nonalcoholic steatohepatitis by deleting genes encoding interacting nuclear envelope and endoplasmic reticulum proteins from mouse hepatocytes. In addition to my basic research, I have been active in the nuclear envelope research field by serving on the NIH Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section and the NIH Action Plan for the Muscular

Dystrophies Mechanisms of Muscular Dystrophy Working Group Section on myopathies caused by mutations on genes encoding nuclear envelope proteins. I also serve on the Scientific Advisory Board of MNG Laboratories, which provides human diagnostics services, including Next Generation Sequencing. My overall goal is to better integrate cell biological approaches into precision medicine and genomics research. Select Publications: Shin JY, Hernandez-Ono A, Fedotova T, Östlund C, Lee MJ, Gibeley SB, Liang CC, Dauer WT, Ginsberg HN, Worman HJ. Nuclear envelope-localized torsinA-LAP1 complex regulates hepatic VLDL secretion and steatosis. J Clin Invest. 2019 Aug 13;130:4885-4900. PMID: 31408437

Worman HJ, Michaelis S. Permanently Farnesylated Prelamin A, Progeria, and Atherosclerosis. Circulation. 2018; 138(3):283-286. PMID: 30012702

Wang Y, Lichter-Konecki U, Anyane-Yeboa K, Shaw JE, Lu JT, Östlund C, Shin JY, Clark LN, Gundersen GG, Nagy PL, Worman HJ. A mutation abolishing the ZMPSTE24 cleavage site in prelamin A causes a progeroid disorder. J Cell Sci. 2016; 129(10):1975-80 PMID:27034136 Kelley Yan MD PhD Silberberg Assistant Professor of Medicine, Genetics and Development

I am a physician-scientist trained in diverse disciplines including clinical gastroenterology, structural biology and stem cell biology. This background provides me with a unique perspective and opportunity to study intestinal stem cell (ISC) biology at the molecular, cellular and tissue levels. My love of science grew from an appreciation of studying undergraduate chemistry and physical sciences. During my graduate school education, this evolved into a desire to understand how 3D structure or molecular form enables biological function in order to confer specificity in protein-protein or protein-nucleic acid interactions. Specifically, I have experimentally examined these interactions in signal transduction, including ligand/receptor interactions, using structural biology

and biophysical methods. My medical training armed me with a love for clinical gastroenterology and guided me toward the field of regenerative medicine to feed my personal desire to serve the patients I see in my clinic. As a postdoctoral fellow, I pursued further scientific training in ISC biology and learned to use rigorous mouse genetics, in vivo models, ex vivo 3D organoid culture models, and single-cell genomics to examine stem cell fate decisions. I have conducted studies to highlight functional differences among ISC populations identified by different markers. These studies were followed up by investigations into the signaling pathways that regulate the behavior of these ISC populations using structural biology and biochemical approaches to perturb these pathways in vivo. As an independent investigator studying intestinal stem cell biology and tissue regeneration, I aim to use my multi-disciplinary training to better understand the basis of human diseases and their possible therapies. Select Publications: Pont AR, Yan KS. Intestinal Crypts Assume the Fetal Position in Response to Injury. Cell Stem Cell. 2018; 23(2):158-159. PMID: 30075126

Yan KS, Gevaert O, Zheng GXY, Anchang B, Probert CS, Larkin KA, Davies PS, Cheng ZF, Kaddis JS, Han A, Roelf K, Calderon RI, Cynn E, Hu X, Mandleywala K, Wilhelmy J, Grimes SM, Corney DC, Boutet SC, Terry JM, Belgrader P, Ziraldo SB, Mikkelsen TS, Wang F, von Furstenberg RJ, Smith NR, Chandrakesan P, May R, Chrissy MAS, Jain R, Cartwright CA, Niland JC, Hong YK, Carrington J, Breault DT, Epstein J, Houchen CW, Lynch JP, Martin MG, Plevritis SK, Curtis C, Ji HP, Li L, Henning SJ, Wong MH & Kuo CJ. Intestinal enteroendocrine lineage cells possess homeostatic and injury-inducible stem cell activity. Cell Stem Cell. 2017 Jul6;21(1):78-90. PMID 28686870.

Yan KS, Janda CY, Chang J, Zheng GXY, Larkin KA, Luca VC, Chia LA, Mah AT, Han A, Terry JM, Ootani A, Roelf K, Lee M, Yuan J, Li X, Bolen CR, Wilhelmy J, Davies PS, Ueno H, von Furstenberg RJ, Belgrader P, Ziraldo SB, Ordonez H, Henning SJ, Wong MH, Snyder MP, Weissman IL, Hsueh AJ, Mikkelsen TS, Garcia KC, Kuo CJ. Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal. Nature. 2017; 545(7653):238-242. PMID: 28467820 Xiao Zhao MD Assistant Professor of Medicine

My long-term goal is to understand how cellular heterogeneity contributes to the pathogenesis of human liver disease using cholangiocyte biology as a platform. It is increasingly evident that cholangiocytes comprise a highly dynamic population of cells with morphologically and functionally distinct subtypes that arise from different developmental origins. Similarly, cholangiopathies refer to a diverse group of disorders that impair biliary cellular homeostasis with varying etiologies and pathology. The overarching vision of my research program will be to understand how these cells differ and the molecular mechanisms underlying cell type-specific properties and associated disease

phenotypes. My earlier work focused on elucidating the molecular mechanisms of biliary atresia (BA), a neonatal

cholangiopathy, by utilizing a newly identified plant electrophile (biliatresone) that was linked casually to naturally occurring BA epidemics in newborn livestock. This work has resulted in three major advances: (i) a novel in vivo model of BA; (ii) unprecedented insights into mechanisms underlying early cholangiocyte injury; (iii) how cell type-specific characteristics can drive a biliary disease phenotype. I joined the faculty at Columbia University Vagelos College of Physicians and Surgeons as Assistant Professor of Medicine (Tenure Track) in Jan 2020. Current and future research efforts at Columbia will be focused on further defining the role of aberrant stress signaling in modulating cholangiocyte injury, elucidating the molecular mechanisms underlying cell type-specific stress responses and developing additional models of human BA. Select Publications: Zhao X, Lorent K, Escobar-Zarate D, Rajagopalan R, Loomes KM, Gillespie K, Mesaros C, Estrada M, Blair I, Winkler J, Spinner NB, Devoto M, Pack M. Protein Quality Control is a Risk Factor and Therapeutic Target in Toxin-Induced Biliary Atresia. 2019 BioRxiv 821967 doi: https://doi.org/10.1101/821967

Estrada MA, Zhao X, Lorent K, Kriegermeier A, Nagao SA, Berritt S, Wells RG, Pack M, Winkler JD. Synthesis and Structure-Activity Relationship Study of Biliatresone, a Plant Isoflavonoid That Causes Biliary Atresia. ACS Med Chem Lett. 2017; 9(1):61-64. PMID: 11149923

Zhao X, Lorent K, Wilkins BJ, Marchione DM, Gillespie K, Waisbourd-Zinman O, So J, Koo KA, Shin D, Porter JR, Wells RG, Blair I, Pack M. Glutathione antioxidant pathway activity and reserve determine toxicity and specificity of the biliary toxin biliatresone in zebrafish. Hepatology. 2016; 64(3):894-907. PMID: 27102575 RESEARCH FACULTY WITH ADDITIONAL PRIMARY APPOINTMENTS Anil K. Rustgi MD Interim Executive Vice-President and Dean of the Faculties of Health Sciences and Medicine, Irving Professor of Medicine, Director, Herbert Irving Comprehensive Cancer Center

Research: Our group has been dedicated with passion to the elucidation of mechanisms underlying GI epithelial biology as well as precancerous conditions. We are interested in tumor initiation, the tumor microenvironment, and tumor metastasis. As part of this effort, our group has developed innovative 3D organoid culture model systems, xenograft implantation (subcutaneous and orthotopic) and genetically engineered mouse models, especially those that reflect cancers of the esophagus, pancreas and colon. We seek to translate these discoveries into novel and innovative diagnostics and therapeutics. We have published extensively in these topics in Cancer Cell, Developmental Cell, Genes

and Development, JCI, PNAS, Nature, Nature Genetics, Nature Protocols, and Gastroenterology. Our work bridges basic science to translational medicine; and includes clinical studies in the genetics of hereditary GI cancers. Additionally, our efforts in GI epithelial biology research have spawned our lab personnel obtaining independent faculty positions with their own federal funding. Select Publications: Reichert M, Bakir B, Moreira L, Pitarresi JR, Feldmann K, Simon L, Suzuki K, Maddipati R, Rhim AD, Schlitter AM, Kriegsmann M, Weichert W, Wirth M, Schuck K, Schneider G, Saur D, Reynolds AB, Klein-Szanto AJ, Pehlivanoglu B, Memis B, Adsay NV, Rustgi AK. Regulation of Epithelial Plasticity Determines Metastatic Organotropism in Pancreatic Cancer. Developmental Cell 2018 Jun 18;45(6):696-711. PMID:29920275

Chatterji P, Hamilton KE, Liang S, Andres SF, Wijeratne HRS, Mizuno R, Simon LA, Hicks PD, Foley SW, Pitarresi JR, Klein-Szanto AJ, Mah AT, Van Landeghem L, Gregory BD, Lengner CJ, Madison BB, Shah P, Rustgi AK. The LIN28B-IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine. Genes and Development 2018 Aug 1;32(15-16):1020-1034. PMID:30068703

Stairs DB, Bayne LJ, Rhoades B, Vega ME, Waldron TJ, Kalabis J, Klein-Szanto A, Lee JS, Katz JP, Diehl JA, Reynolds AB, Vonderheide RH, Rustgi AK. Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene. Cancer Cell 2011 Apr 12;19(4):470-83. PMID:21481789 Govind Bhagat MD Professor of Pathology and Cell Biology Director, Hematopathology Division I am a board-certified pathologist with a specialization in hematopathology and celiac disease pathology. My areas of expertise and conditions treated include: lymphomas, leukemia, hematopathology, anatomic pathology, laboratory medicine, celiac disease, myelodysplastic disorders, immunohistochemistry, essential thrombocythemia, multiple myeloma, Castleman disease, spleen diseases, immunocompromised host diseases, HIV-related blood disorders,

hematopoiesis, bone marrow disorders and molecular cancer. My research areas encompass pathogenesis and genetic characteristics of lymphomas, leukemias and myeloid disorders, and immunopathogenesis of celiac disease. Select Publications: Shao Z, Flynn RA, Crowe JL, Zhu Y, Liang J, Jiang W, Aryan F, Aoude P, Bertozzi CR, Estes VM, Lee BJ, Bhagat G, Zha S, Calo E. DNA-PKcs has KU-dependent function in rRNA processing and haematopoiesis. Nature, 2020; 579(7798):291-296. PMID: 32103174

Soderquist CR, Patel N, Murty VV, Betman S, Aggarwal N, Young KH, Xerri L, Leeman-Neill R, Lewis SK, Green PH, Hsiao S, Mansukhani MM, Hsi ED, de Leval L, Alobeid B, Bhagat G. Genetic and phenotypic characterization of indolent T-cell lymphoproliferative disorders of

the gastrointestinal tract. Haematologica. 2019 doi: 10.3324/haematol.2019.230961. PMID: 31558678

Hussein S, Gindin T, Lagana SM, Arguelles-Grande C, Krishnareddy S, Alobeid B, Lewis SK, Mansukhani MM, Green PHR, Bhagat G. Clonal T cell receptor gene rearrangements in coeliac disease: implications for diagnosing refractory coeliac disease. J Clin Pathol. 2018 Sep;71(9):825-831. PMID: 29703761 Yiping W. Han, PhD Professor of Microbial Sciences in Dental Medicine, Microbiology and Immunology

I am a tenured professor of microbial sciences with an interdisciplinary appointment at Columbia University Medical Center and the Vagelos College of Physicians & Surgeons. My research has been consistently funded by the NIH and involves the role of microbes in human health and disease. My research interests include host-pathogen interactions, human microbiome and oral-systemic connections. The human microbiome is a vast population of microbes that play an essential role in health and disease. Work in our laboratory is focused on the following aspects: (i) investigating the role of oral bacteria in extra-oral infection and inflammation; (ii) investigating the mechanisms of

Fusobacterium nucleatum pathogenesis in pregnancy complications and gastrointestinal cancers; and (iii) developing genetic tools for mutant construction in bacteria. Select Publications: Rubinstein, M.R., Baik, J.E., Lagana, S.M., Han, R.P., Raab, W.J., Sahoo, D., Dalerba, P., Wang, T.C. and Han, Y.W. (2019) Fusobacterium nucleatum promotes colorectal cancer through induction of novel Wnt/b-catenin modulator Annexin A1 in proliferating cancerous cells. EMBO Reports doi.org/10.15252/embo.201847638.1. PMID:30833345

Garcia-So, J., Zhang, X., Yang, X., Rubinstein, M.R., Mao, D.Y., Kitajewski, J, Liu, K. and Han, Y.W. (2019) Omega-3 fatty acids suppress Fusobacterium nucleatum-induced placental inflammation originating from maternal endothelial cells. JCI Insight 4: e125436. doi.org/10.1172/jci.insight.125436. PMID: 30728337

Vander Haar, E.L., So, J., Gyamfi-Bannerman, C. and Han, Y.W. (2018) Fusobacterium nucleatum and adverse pregnancy outcomes: Epidemiological and mechanistic evidence. Anaerobe 50: 55-59. PMID: 29409815 Chin Hur MD MPH Irving Professor of Medicine Professor of Epidemiology

I am a practicing gastroenterologist and a cancer health outcomes researcher. I am a physician scientist and a Professor of Medicine and Epidemiology at Columbia University and co-leader of the Prevention, Control, and Disparities Program for the Herbert Irving Comprehensive Cancer Center at Columbia. Since 2010, I have served on the NCI’s Cancer Intervention and Surveillance Modeling Network (CISNET) steering committee. Many of our modeling analyses have made significant contributions to inform clinical and public policy guidelines. I have experience in simulation modeling related to gastrointestinal cancers and also in many other areas such as outcomes and cost-effectiveness analyses that help test clinical management strategies in celiac disease. The overarching

goal of my research as a physician-scientist is to improve clinical care for patients with cancer and to improve cancer control on a population level. I propose to achieve this goal by performing analyses that leverage the diverse health outcomes methods and techniques that my research team and I have gained expertise in. Select Publications: Jang SR, Truong H, Oh A, Choi J, Tramontano AC, Laszkowska M, Hur C. Cost-effectiveness Evaluation of Targeted Surgical and Endoscopic Therapies for Early Colorectal Adenocarcinoma Based on Biomarker Profiles.JAMA Netw Open. 2020 Mar 2;3(3):e1919963. doi: 10.1001/jamanetworkopen.2019.19963. PMID: 32150269

Laszkowska M, Oh A, Hur C. Screening for Upper Gastrointestinal Malignancies in the United States—Which Immigrant Groups Should Be Considered High-Risk? Gastroenterology. 2020 Jan;158(1):4-8. doi: 10.1053/j.gastro.2019.09.047. PMID: 31614125

Chu JN, Choi J, Ostvar S, Torchia JA, Reynolds KL, Tramontano A, Gainor JF, Chung DC, Clark JW, Hur C. Cost-effectiveness of immune checkpoint inhibitors for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Cancer. 2019 Jan 15;125(2):278-289. PMID: 30343509

CLINICAL RESEARCH Julian A. Abrams MD MS Associate Professor of Medicine and Epidemiology

Dr. Abrams is a clinical, epidemiological, and translational researcher with a focus on risk factors for esophageal and other upper gastrointestinal cancers. He obtained a K07 Career Development Award from the National Cancer Institute, is a Program Director on a U54 award from the NCI as part of a multicenter consortium to perform translational research in Barrett’s esophagus, and has a R01 assessing an oral microbiome signature to identify patients at risk for esophageal cancer. Dr. Abrams’ current areas of research include: the role of the oral and esophageal microbiome in Barrett’s esophagus and progression to cancer; identification of novel markers of tissue at risk for esophageal adenocarcinoma; novel endoscopic technologies for treatment and imaging of Barrett’s esophagus (BE); predictors of response and recurrence after endoscopic ablation therapy for BE.

Select Publications: Snider EJ, Compres G, Freedberg DE, Khiabanian H, Nobel YR, Stump S, Uhlemann AC, Lightdale CJ, Abrams JA. Alterations to the esophageal microbiome associated with progression from Barrett’s esophagus to esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2019; 28(10):1687-1693. PMID: 31466948

Snider EJ, Freedberg DE, Abrams JA. Potential role of the microbiome in Barrett’s esophagus and esophageal adenocarcinoma. Dig Dis Sci. 2016 Aug;61(8):2217-2225. PMID: 27068172

Freedberg DE, Yang YX, Abrams JA. Proton pump inhibitors and myocardial infarction. Gastroenterology. 2015 Oct;149(4):830-3. PMID: 26277262 Daniel E. Freedberg, MD, MS Assistant Professor of Medicine and Epidemiology

I am a clinical and translational investigator focused on enteric infections and the gastrointestinal microbiome in the setting of critical illness. I have experience in molecular laboratory research, clinical training as a physician, a dual appointment in Medicine and Epidemiology, and am the recipient of several grants supporting ICU-based human subjects research focused around enteric colonization in the ICU. With funding from the NIH, the American Gastroenterological Association (AGA), and the Department of Defense, I have built large ICU patient cohorts containing longitudinal clinical data, serial rectal swabs, whole stools, and other bio-samples. These data have allowed us to interrogate the dynamic changes that take place within the gastrointestinal microbiome during

critical illness and to ask how these changes may impact risk for ICU-acquired infections. Our preliminary studies show that colonizing enteric organisms such as vancomycin-resistant Enterococcus (VRE) are important determinants of patients’ subsequent risk for infection. We have also found that colonizing enteric organisms can change health outcomes for patients who share the same hospital environment, even if these neighboring patients are not themselves colonized. The normal native microbiota resists colonization with VRE, C. difficile, and similar multidrug-resistant or antibiotic-associated organisms, and a major focus of our current work is how to augment enteric colonization resistance in the face of ICU antibiotics. Select Publications: Wang Y, Schluger A, Li J, Gomez-Simmonds A. Salmasian H, Freedberg D. Does addition of intravenous metronidazole to oral vancomycin improve outcomes in clostridioides difficile infection? Clin Infect Dis. 2019 pii: ciz1115. doi: 10.1093/cid/ciz1115. PMID: 31714955

Freedberg DE, Zhou MJ, Cohen ME, Annavajhala MK, Khan S, Moscoso DI, Brooks C, Whittier S, Chong DH, Uhlemann AC, Abrams JA. Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection. Intensive Care Med. 2018; 44(8):1203-1211. PMID: 29936583

Seeley JJ, Baker RG, Mohamed G, Bruns T, Hayden MS, Deshmukh SD, Freedberg DE, Ghosh S. Induction of innate immune memory via microRNA targeting of chromatin remodelling factors. Nature. 2018; 559(7712):114-119. PMID: 29950719

http://www.ncbi.nlm.nih.gov/sites/myncbi/daniel.freedberg.1/bibliography/43541260/public/?sort=date&direction=ascending Peter H. R. Green MD Phyllis and Ivan Seidenberg Professor of Medicine I am a clinician-investigator specializing in the field of celiac disease and in 2001 I founded the Celiac Disease Center at Columbia University Medical Center. The Center now includes adult and pediatric gastroenterologists, dieticians, research coordinators; and has active research collaborations worldwide to study the epidemiology, clinical manifestations and the pathophysiological mechanisms of celiac disease. I have authored a book for the lay public, “Celiac

disease, a hidden epidemic” and have co-authored more than 250 peer-reviewed publications on the topic of celiac disease, including epidemiological investigations, studies of associated diseases, pathophysiology, and clinical trials of non-dietary drug therapy. Select publications: Myleus A, Reilly NR, Green PHR. Rate, risk factors and outcomes of nonadherence in pediatric patients with celiac disease: a systematic review. Clin Gastroenterol Hepatol. 2020;18(3):562-573. doi: 10.1016/j.cgh.2019.05.046. PMID: 31173891

Walker MD, Williams J, Lewis SK, Bai JC, Lebwohl B, Green PHR. Measurement of Forearm Bone Density by Dual Energy X-Ray Absorptiometry Increases the Prevalence of Osteoporosis in Men With Celiac Disease. Clin Gastroenterol Hepatol. 2020 Jan;18(1):99-106. PMID: 30981003

Wolf RL, Lebwohl B, Lee AR, Zybert P, Reilly NR, Cadenhead J, Amengual C, Green PHR. Hypervigilance to a Gluten-Free Diet and Decreased Quality of Life in Teenagers and Adults with Celiac Disease. Dig Dis Sci. 2018 Jun;63(6):1438-1448. PMID: 29387990 Fay Kastrinos MD Associate Professor of Medicine

Dr. Kastrinos is a clinical gastroenterologist with interests related to the genetics, screening and primary prevention of gastrointestinal tumors, primarily colorectal and pancreatic cancer. She has expertise in the genetic evaluation of patients at risk for hereditary gastrointestinal cancer syndromes and directs a multi-disciplinary specialty clinic at the Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, for genetic risk assessment and cancer prevention in familial gastrointestinal syndromes. She has expertise in clinical cancer genetics, statistical methodology involving the genetic epidemiology of cancer predisposition syndromes, development of prediction models and analyses of large databases. Her research focus complements her clinical

interests and involves optimizing the identification of patients with inherited cancer syndromes and promoting existing and testing novel cancer screening and prevention strategies. She has led large-scale studies, multiple national and international collaborations in developing tools to improve genetic risk assessment for inherited colorectal and pancreatic cancers and developing guidelines for optimal surveillance strategies for individuals at high risk for these cancers. She serves as site-PI at Columbia University for the (i) Cancer of the Pancreas Screening (CAPS) multicenter consortium (U01); (ii) Circulating Biomarker Consortium for the Early Detection of Pancreatic Cancer (U01); (iii) international prospective clinical trial for the validation of a novel biomarker for the early diagnosis of pancreatic cancer in high risk individuals with familial pancreatic cancer (Immunovia-PanFAM1). Select Publications: Kastrinos F, Samadder NJ, Burt RW. Use of Family History and Genetic Testing to Determine Risk of Colorectal Cancer. Gastroenterology. 2020; 158(2):389-403. PMID: 31759928

Yurgelun MB, Kastrinos F. Tumor Testing for Microsatellite Instability to Identify Lynch Syndrome: New Insights Into an Old Diagnostic Strategy.J Clin Oncol. 2019; 37(4):263-265. PMID: 30550362

Hasan A, Moscoso DI, Kastrinos F. The role of genetics in pacreatitis. Gastrointest Endosc Clin N Am. 2018; 28(4):587-603. PMID: 30241646 Suneeta Krishnareddy MD MS Assistant Professor of Medicine

I am a gastroenterologist and translational researcher in the division of gastroenterology in the Department of Medicine at Columbia University, where I also completed my fellowship. In addition, I work in a mucosal immunology laboratory in the Division of Microbiology and Immunology at Columbia University Medical Center studying the effects of NfkB signaling in the body. My translational research interests are focused on understanding the pathogenesis of inflammatory and autoimmune disorders of the gut, mucosal innate immune responses and molecular alterations associated with celiac disease and inflammatory bowel disease. The research is performed both in my laboratory, and

as interdisciplinary collaborations with investigators at Columbia and at other centers. I am adept at performing and analyzing immunohistochemical stains, in situ hybridization, flow cytometry, and a variety of molecular biologic assays on human and murine specimens/tissues. I also oversee and organize the collection and banking of intestinal lymphocyte fractions, peripheral blood mononuclear cells, and serum from patients for basic and translational research endeavors.

Select publications: Krigel A, Patel A, Kaplan J, Kong XF, Garcia-Carrasquillo R, Lebwohl B, Krishnareddy S. Anesthesia Assistance in Screening Colonoscopy and Adenoma Detection Rate Among Trainees. Dig Dis Sci. 2020; 65(4):961-968. PMID: 31485995

Krishnareddy S. The microbiome in celiac disease. Gastroenterol Clin North Am. 2019; 48(1):115-126. PMID: 30711204

Krishnareddy S, Stier K, Recanati M, Lebwohl B, Green PH. Commercially available glutenases: a potential hazard in coeliac disease.Therap Adv Gastroenterol. 2017; 10(6):473-481. PMID: 28567117 Benjamin Lebwohl MD MS Associate Professor of Medicine and Epidemiology I am a clinical gastroenterologist with a research focus on the epidemiology of celiac disease, with a specific focus on risk

factors, quality and outcomes. During my training in preventive oncology and population sciences in an NCI-funded fellowship under the mentorship of Alfred I. Neugut, I performed studies in bowel preparation prior to colonoscopy and adherence to biopsy standards in the diagnosis of celiac disease. I have used the analytical skills gained from that fellowship and from the master’s degree in Patient Oriented Research to study these conditions using large data sets from the US and Sweden. My research activities include the conduct of epidemiologic analyses including cohort and case-control studies, and clinical trials. Select Publications:

Krigel A, Prasad VK, Lebwohl B. News Coverage of the American Cancer Society's Update to Colorectal Cancer Screening Guidelines. Mayo Clin Proc. 2020; 95(3):617-618. PMID: 32138893

Wolf RL, Morawetz M, Lee AR, Koch P, Contento IR, Zybert P, Green PHR, Lebwohl B. A Cooking-Based Intervention Promotes Gluten-Free Diet Adherence and Quality of Life for Adults with Celiac Disease. Clin Gastroenterol Hepatol. 2019 Sep 20. pii: S1542-3565(19)31024-9. PMID: 31546057

Axelrad JE, Joelson A, Green PHR, Lawlor G, Lichtiger S, Cadwell K, Lebwohl B. Enteric Infections Are Common in Patients with Flares of Inflammatory Bowel Disease. Am J Gastroenterol. 2018 Oct;113(10):1530-1539. PMID: 30072777 Charles J. Lightdale MD Professor of Medicine I am a trained gastroenterologist with clinical expertise in the areas of pancreatic cancer, Barrett’s esophagus and other related diseases. My specialties include digestive and liver disorders, gastroenterology and cancer. I have authored over 130 scientific articles in peer-reviewed journals, 290 reviews, editorials and book chapters. I have served on two consecutive 4-year terms as Editor-in-Chief of Gastrointestinal Endoscopy, the official journal of the ASGE.

Identifying ways to prevent upper-GI cancers is the main goal of my research. My research areas include studying Barrett's esophagus; targeted biopsies using confocal endomicroscopy for more accurate diagnosis; radiofrequency ablation of Barrett's esophagus; endoscopic mucosal resection of pre-cancerous lesions and early cancer. I have also worked extensively on developing blood and biopsy tests for early detection and prevention of esophageal cancers; and use of endoscopic ultrasound for diagnosis and staging of gastrointestinal cancers. Select Publications: Lightdale CJ. Gastroesophageal Reflux Disease: Changing the Conversation. Gastrointest Endosc Clin N Am. 2020 Apr;30(2):xi-xii. doi:

10.1016/j.giec.2020.02.001. PMID: 32146952

Ginès A, Lightdale CJ. How I do a diagnostic EUS. Endoscopy. 2019; 51(10):973-975. PMID: 31307101

Goldblum JR, Shaheen NJ, Vennalaganti PR, Sharma P, Lightdale CJ. WATS for Barrett’s surveillance. Gastrointest Endosc. 2018 Jul;88(1):201-202. PMID: 29935618 John M. Poneros MD Associate Professor of Medicine

I am a trained interventional endoscopist who performs invasive pancreatico-biliary procedures. I serve as the Acting Director of Endoscopy at New York Presbyterian Hospital/Columbia and the Acting Clinical Chief of the Division of Digestive and Liver Diseases. With a gift from the Diller von Furstenberg Family Foundation, I established the Pancreatitis Program at New York Presbyterian Hospital/Columbia. My research interests include the study of Barrett’s esophagus, pancreatico-biliary diseases and endoscopic techniques. I am currently a site PI on an NIH funded study using a catheter based optical coherence tomography imaging system in Barrett’s esophagus.

Select Publications: Cui Y, Khanna LG, Saqi A, Crapanzano JP, Mitchell JM, Sethi A, Gonda TA, Kluger MD, Schrope BA, Allendorf J, Chabot JA, Poneros JM. The Role of Endoscopic Ultrasound-Guided Ki67 in The Management of Non-Functioning Pancreatic Neuroendocrine Tumors. Clin Endosc. 2019 Jul 15. doi: 10.5946/ce.2019.068. PMID: 31302988

Guo A, Poneros JM. The role of endotherapy in recurrent acute pancreatitis. Gastrointest Endosc Clin N Am. 2018; 28(4):455-476. PMID: 30241638

Poneros JM, Faye AS, Barr Fritcher EG, Sen A, Anandasabapathy S, Bresalier RS, Marcon N, Turgeon DK, Appelman H, Normolle D, Morrison LE, Brenner DE, Halling KC. Dig Dis Sci. 2017; 62(5):1216-1222. PMID: 28265829 Amrita Sethi MD Associate Professor of Medicine

I am an Associate Professor of Medicine at the Division of Digestive Diseases at Columbia University Medical Center. I received my degree in Medicine from the State University of New York, followed by a residency program in New England Medical Center Boston and Fellowships in Medical College of Virginia and the University of Colorado Health Sciences Center. I specialize in digestive & liver disorders, gastroenterology and cancer. I am interested in the endoscopic treatment of pancreaticobiliary diseases, benign and malignant, through the use of new devices and novel applications of existing methods. Furthermore, we currently have a clinical trial in progress on per-

oral cholangioscopy (POCS) in liver transplantation patients. Select Publications: Sethi A, Tyberg A, Slivka A, Adler DG, Desai AP, Sejpal DV, Pleskow DK, Bertani H, Gan SI, Shah R, Arnelo U, Tarnasky PR, Banerjee S, Itoi T, Moon JH, Kim DC, Gaidhane M, Raijman I, Peterson BT, Gress FG, Kahaleh M. Digital Single-operator Cholangioscopy (DSOC) Improves Interobserver Agreement (IOA) and Accuracy for Evaluation of Indeterminate Biliary Strictures: The Monaco Classification. J Clin Gastroenterol. 2020 Feb 7. doi: 10.1097/MCG.0000000000001321. PMID: 32040050

Visrodia K, Sethi A. How to Learn and Perform Endoscopic Submucosal Dissection and Full-Thickness Resection in the Colorectum in the United States. Gastrointest Endosc Clin N Am. 2019; 29(4):647-657. PMID: 31445688

Axelrad JE, Lichtiger S, Sethi A. Treatment of Crohn's Disease Anastomotic Stricture with a Lumen-apposing Metal Stent. Clin Gastroenterol Hepatol. 2018 Mar;16(3):A25-A26. PMID: 28529163 Elizabeth C. Verna, MD, MSc Associate Professor of Medicine Dr. Verna is an Associate Professor of Medicine in the Center for Liver Disease and Transplantation and Division of Digestive and Liver Diseases of Columbia University. She has an active clinical practice involving all forms of chronic

liver disease as well as decompensated cirrhosis and liver transplantation. She has a significant clinical research focus, including NIH funding to study the impact of the intestinal microbiome on liver disease and liver transplantation as well as participation in multiple NIH-funded multicenter and multidisciplinary studies. In addition, she has significant expertise in clinical trials and is the Director of Clinical Research for the Columbia University Transplant Clinical Research Center, a center that supports transplant-related investigators across Department and Divisions at Columbia with has over 100 studies ongoing. Finally, Dr. Verna is active in national and international societies,

including recently being elected to the Board of Directors for the American Society of Transplantation. Select Publications: Rosenblatt R, Verna EC. Cystatin C: The answer or a call for better kidney biomarkers in cirrhosis? Transplantation. 2020 Mar 6. doi: 10.1097/TP.0000000000003223. PMID: 32150033

Duan Y, Llorente C, Lang S, Brandl K, Chu H, Jiang L, White RC, Clarke TH, Nguyen K, Torralba M, Shao Y, Liu J, Hernandez-Morales A, Lessor L, Rahman IR, Miyamoto Y, Ly M, Gao B, Sun W, Kiesel R, Hutmacher F, Lee S, Ventura-Cots M, Bosques-Padilla F, Verna EC, Abraldes JG, Brown RS Jr, Vargas V, Altamirano J, Caballería J, Shawcross DL, Ho SB, Louvet A, Lucey MR, Mathurin P, Garcia-Tsao G, Bataller R, Tu XM, Eckmann L, van der Donk WA, Young R, Lawley TD, Stärkel P, Pride D, Fouts DE, Schnabl B. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature. 2019; 575(7783):505-511. PMID: 31723265

Cullaro G, Pisa JF, Brown RS Jr, Wagener G, Verna EC. Early Postoperative Neutrophil Gelatinase-Associated Lipocalin Predicts the Development of Chronic Kidney Disease After Liver Transplantation. Transplantation. 2018; 102(5):809-815. PMID: 29300232 Julia Wattacheril, MD, MPH Associate Professor of Medicine Dr. Wattacheril is an Associate Professor of medicine and Director of the Nonalcoholic Fatty Liver Disease (NAFLD) Program in the Center for Liver Disease and Transplantation. Her primary Translational science interests include: 1) investigating the relationship between lipids and proteins within the context of the development and progression of nonalcoholic steatohepatitis, 2) optimizing the clinical care of patients with NAFLD pre and post transplantation, 3) understanding the

relationship between NAFLD and hepatocellular carcinoma and 4) enhancing the care of liver disease patients using genomics and electronic health record phenotyping. She mentors several residents and gastroenterology fellows in addition to computational geneticists, nurse practitioners, dietitians and anyone interested in enhancing the integrated knowledge and care for patients with chronic liver disease. Select Publications: Phipps M, Livanos A, Guo A, Pomenti S, Yeh J, Dakhoul L, Burney H, Kettler C, Liu H, Miller E, Gawrieh S, DeLemos A, Scanga A, Chalasani N, Wattacheril J. "Gender Matters: Characteristics of Hepatocellular Carcinoma in Women from a Large, Multicenter Study in the United

States." Accepted for publication in American Journal of Gastroenterology. Wattacheril J. Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease.Gastroenterol Clin North Am. 2020 Mar;49(1):141-149. PMID: 32033760

Gawrieh S, Dakhoul L, Miller E, Scanga A, deLemos A, Kettler C, Burney H, Liu H, Abu-Sbeih H, Chalasani N, Wattacheril J. Characteristics, aetiologies and trends of hepatocellular carcinoma in patients without cirrhosis: a United States multicentre study. Aliment Pharmacol Ther. 2019; 50(7):809-821. PMID: 31475372