Cedars-Sinai IBD Genetic Research Center

Dermot McGovern, MD, PhD, FRCP(Lon)

Principal Investigator

Professor, Medicine and Biomedical Sciences

Director, Translational Research in the Inflammatory Bowel and Immunobiology Research Institute

Co-investigators

  • Talin Haritunians PhD (Genomics)
  • Thad Stappenbeck MD PhD (Epithelial Biology)
  • Dalin Li PhD (Advanced Genomic Statistics)
  • Ta-Chiang Liu MD PhD (Paneth Cells)
  • Simon Gayther PhD (Functional Genomics)
  • Dennis Hazelett PhD (Systems Biology)
  • Arkadiusz Gertych PhD (Computational Pathology)
  • Shishir Dube (Advanced Statistical Approaches to Imaging)
  • Alka Potdar PhD (Transcriptomics)
  • Jonathan Braun MD PhD (Mucosal/microbiome interaction)
  • Janine Bilsborough PhD (Drug Discovery)
  • Stephan Targan MD (Clinician)

Additional Lead Clinicians

  • Gil Melmed
  • Phil Fleshner (surgeon)
  • Shervin Rabizadeh and David Ziring (Pediatrics)
  • Cindy Kallman (Radiology)
  • Elena Chang (Pathology)
  • Eric Vasiliauskas
  • Tina Ha
  • Gaurav Syal
  • Nirupama Bonthala

Clinical Coordinators

  • Mary Hanna
  • Justina Ibrahim
  • Valeriya Pozdnyakova

Lab Team Members

  • Emebet Mengesha (Lab Manager)
  • Philip Debbas
  • Shell Shaohong (Phenotyper)

Specific Aim 1: Define genetic determinants of unmet medical needs in IBD. Sub-aim 1a: Define genetic factors associated with true non-response (TNR), pharmacokinetic, and immunogenic parameters of biologic therapies in IBD. Sub-aim 1b: Define genetic variation associated with perianal Crohn’s disease.

Specific Aim 2: Functional characterization of genetic risk variants associated with IBD. Sub-aim 2a: Characterization of the regulatory landscape in ileal CD tissues. Sub-aim 2b: Functional characterization of tissue specific regulatory and transcriptomic landscapes for IBD risk loci. Expression quantitative trait locus (eQTL) analysis of IBD risk regions. Connecting IBD-associated regulatory variants to target genes using chromosome conformation capture assays.

Specific Aim 3: Defining novel genetic determinants and environment interplay of Paneth cell phenotypes in CD patients. Determine the genetic associations, molecular mechanisms, and clinical relevance of Paneth cell defects in European ancestry, East Asian, African American, and Hispanic IBD patients.

Administrative Supplement

Aim 1: To quantify histomorphometric (HM) features within tissue architecture that are associated with disease recurrence following surgery for CD. Each category requires separate training data to develop a single classification algorithm that identifies all categories of interest at once in whole slide H&E images.

Aim 2: To determine the molecular underpinnings and genetic associations of HM features in CD and build prediction models for disease recurrence with integration of HM, genomic, clinical and transcriptomic features.

Ancillary liaisons

Jon Braun (Cedars): Biomarking IBD patient-specific disease features using the epithelial antigenic peptidome


Additional resources at Cedars-Sinai

  • MIRIAD Biorepository: Contains over 15K IBD research subjects (includes extended families), for whom ~12,000 have whole exome or whole genome sequence data and GSA data. All subjects are consented for ‘call-backs’ for additional sampling as well as access to medical charts, radiology, histopathology etc.
  • EBV Transformed Lymphoblastoid Cell Line Bank in ~15,000 subjects with WES and GSA in ~12,000. Capabilities to ‘drive’ these to IPSCs as well as ‘Gut-on-a Chip’ technology.
  • Computational Pathology and Advanced Approaches to Imaging: Drs. Arkadiusz Gertych and Shishir Dube are bringing advanced computational approaches to histopathology and radiology, respectively, and leading efforts to integrate this with other ‘-omic’ data and clinical data across the GRCs.

Major interests

  • Genetic and genomic studies to identify risk factors for IBD and also to study pleiotropic effects between IBD and other traits immune-mediated, metabolic, infectious, and neurological traits. (Additional collaborators: SARS-CoV2 (CORALE and CLARITY consortia); Parkinson’s Disease (Clive Svendsen))
  • Genotype x Phenotype studies (Collaborators: VEOIBD & SHARE Consortia, Mike Kamm (POCER Study)).
  • Genotype x Microbiome Studies (Additional Collaborators: Suzanne Devkota and David Underhill)
  • Non-Northern European population studies: Ashkenazi Jews, East Asians, African Americans, Hispanics. (Additional Collaborators: Asan Medical Center, Korea; Tohoku University, Japan; Hailiang Hang; Children’s Hospital of LA; MiLAtinX Consortium, Marie Abreu; Esther Torres, University of Puerto Rico)
  • Pharmacogenomics (Additional Collaborators: PANTS Consortium, Tariq Ahmad, Mark Daly)
  • Sex-Specific Influences on IBD pathophysiology and Natural History
 

Co-Investigators

Dr. Thaddeus Stappenbeck, MD, PhD

Professor of Pathology and Immunology, Cleveland Clinic

Dr. Stappenbeck is a practicing pathologist and an internationally recognized leader in the study of epithelial stem cells in inflammatory bowel disease and colorectal cancer. Dr. Stappenbeck was recruited to Cleveland Clinic from Washington University School of Medicine in St. Louis, where he was the Conan Professor of Pathology and Immunology and co-chief of the Division of Laboratory and Genomic Medicine. He earned a combined MD/PhD degree at Northwestern University and completed a residency and fellowship in pathology at Washington University. He is an elected member of several honorary societies, including the Association of American Physicians and American Society for Clinical Investigation.

Ta-Chiang Liu, MD, PhD

Assistant Professor of Pathology & Immunology, Washington University School of Medicine

Dr. Liu is an Assistant Professor of Pathology and Immunology, Division of Anatomic and Molecular Pathology, Washington University School of Medicine. Dr. Liu’s main research interest is in the role of Paneth cells in Crohn’s Disease. In particular, he is interested in the molecular mechanisms of how morphologic patterns of cytoplasmic antimicrobial granules are affected by genetics and environmental triggers, and their clinical relevance. Dr. Liu’s research interests also include developing disease pathogenesis-relevant prognostic biomarkers.

Dr. Simon Gayther, PhD

Professor and Director of Molecular Epidemiology, Cedars-Sinai

Dr. Gayther’s research program is focused largely on understanding the underlying causes of ovarian cancer initiation and development. Dr. Gayther has a long, established track record in defining the heritable component of ovarian cancer, and the functional role of both common and rare risk variants and their target susceptibility genes in the early-stage disease pathogenesis. The overall approach of this research program is to integrate genomics and epigenomics analyses to identify molecular markers associated with disease, with cell biology modeling studies to validate the role of novel molecular markers in disease biology. The goal is to translate the findings from these studies into the clinical arena to improve risk prediction and prevention strategies, early-stage screening and disease diagnosis and targeted therapeutics for patients.

Dr. Dennis Hazelett, PhD

Assistant Professor, Biomedical Sciences, Cedars-Sinai

Dr. Hazelett has a broad background in both experimental and computational biology. He relies on a systems-biology approach involving the analysis and synthesis of next-generation sequencing data. His most recent contributions are highlighted by efforts to annotate and draw inference from the functional consequences of genetic associations from genome-wide association studies (GWAS) for prostate cancer, Hodgkin’s lymphoma and ovarian cancers. Toward this goal, Dr. Hazelett integrated GWAS and next-generation sequencing data from my collaborators with public datasets such as1000 genomes and the Encyclopedia of DNA elements (ENCODE) to infer new diseases variants outside of transcribed sequences. He has recently begun independent efforts as a principal investigator at Cedars-Sinai Medical Center, using novel approaches to achieve a greater understanding of the relationship between the regulatory code and genetic disease variants.

Dr. Arkadiusz Gertych, PhD

Assistant Professor of Surgery, Pathology and Laboratory Medicine, Cedars-Sinai Medical Center

Dr. Gertych’ research interests are focused on computational pathology which he uses as a platform to quantitate morphologic patterns of tumors at the tissue and single cell level to understand functional relationships between cells in the tumor microenvironment. The computational pathology provides opportunities to develop a new class of biomarkers that can be integrated with other -omics data to improve the prediction of disease outcomes and response to treatment in the era of precision medicine. Dr Gertych’s recent scientific contributions are focused on urologic and pulmonary malignancies.

Dr. Jonathan Braun, MD, PhD

Director, IBD Enterprise Operations, Cedars- Sinai Medical Center

A native of Cleveland, Ohio, Dr. Braun was raised in Los Angeles, where he studied violin, and continues his interests in musical performance and poetry. After studies at Stanford University, Harvard Medical School, Brigham and Women’s Hospital, and Whitehead Institute, he joined the faculty at the UCLA School of Medicine, where he served as chair of pathology and laboratory medicine. In 2019, he joined the Inflammatory Bowel and Immunobiology Research Institute of Cedars-Sinai Medical Center, to study human cohort-based biology of mucosal-microbiome interaction in IBD via multi’omic methods. His recent activities included participant or PI roles in NIH HMP2, the CCF Microbiome Consortium, the CORALE SeroNet NCI consortium, and the NIDDK IBD Genetics Consortium. This work has identified allelic variation of IBD-associated loci, notably mucin o-glycan structures, on microbiome composition and function, and mechanisms of pre-disease and disease activity states. His ancillary project with the NIDDK IBD Genetics Consortium searches for genome-wide targets of anti-epithelial autoimmunity, and their potential role in IBD disease phenotypes.