Cedars-Sinai

IBD Genetics Research Center

Dermot McGovern, MD, PhD, FRCP(Lon), FACG

Principal Investigator

Professor, Medicine and Biomedical Sciences

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

Director, Precision Health, Cedars-Sinai

Website

Lead Clinicians

Gil Melmed, MD
Phil Fleshner, MD (surgeon)
Shervin Rabizadeh, MD and David Ziring, MD (Pediatrics)
Cindy Kallman, MD (Radiology)
Elena Chang, MD (Pathology)
Eric Vasiliauskas, MD
Nirupama Bonthala, MD
Phillip Gu, MD
Andres Yarur, MD
University of Southern California: Sarah Sheibanu, MD
University of Southern California: Bing Zhang, MD, MAS
Children’s Hospital Los Angeles: Sonia Michail, MD, FAAP, AGAF
UC San Diego: Siddharth Singh, MD, MS
Houston Methodist: Bincy P. Abraham, MD, MS, AGAF, FACG
The University of Mississippi Medical Center: Sarah C. Glover, DO AGAF
University of Nevada, Reno: Mark S. Riddle, MD, DrPH, FISTM

Lab and Project Management

Emebet Mengesha (Lab Manager)
Shell Shaohong, MD (Phenotyper)

Clinical Coordinators

Mary Hanna
Abdul Khan
Anthony Navarro

Analysts

Dalin Li, PhD
Talin Haritunians, PhD
Shishir Dube, PhD
Sarfaraz Lalani
Minsuk Kim, PhD
Dylan Shiramizu
Ruowang Li, PhD

NIDDK IBDGC-related goals

Specific Aims

Aim 1: Characterize genetic variation and host-microbiome interactions associated with IBD in Hispanics. A) We will build the largest cohort of Hispanic IBD subjects. (Collaboration: MiaLAtinX Consortium) B) We will define common and rare variation associated with IBD in Hispanics including variants identified through admixture mapping (collaboration: Mark Daly). C) Using biomarker-based inference to quantitate peripheral immune responses to up to 1,800 common human gut-resident bacteria and IBD-associated serologies, we will identify host-microbiome in Hispanic IBD.

Aim 2: Identify molecular causes of anti-TNF responsiveness through an integrated resource of both genetic and multi-modal single-cell data. In a prospective cohort of CD patients, we will determine the single-cell proteogenomic signatures and longitudinal single-cell multi-modal transcriptional responses associated with outcomes from anti-TNF therapy.

Aim 3: Use of human intestinal epithelial cell culture systems to screen for function of new IBD susceptibility loci. A substantial number of genes with coding variants associated with CD are highly expressed in the intestinal epithelium. We will generate human intestinal organoids and use novel assays to determine functional consequences of coding-changing variants associated with IBD.

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 corresponding genetic data available in ~12,000 subjects and including capabilities to ‘drive’ cell lines 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.
McGovern Lab Genotyping Facility: The lab is fully equipped with Illumina technology and performs genotyping and thorough quality control on variety of arrays depending on project needs.
Applied Genomics, Computational & Translational (AGCT) Core: Novaseq 6000, NextSeq 500, and MiSeq suite of Illumina next-generation sequencers provides researchers extreme flexibility in a cost-efficient manner. They offer a wide range of read capacity, output, run times, and costs for different sequencing applications. In addition, the core has single cell systems including 10x GENOMICS CHROMIUM CONTROLLER, 10X GENOMICS CHROMIUM CONNECT, BD BIOSCIENCE RHAPSODY SINGLE CELL SYSTEMS, MISSION BIO TAPESTRI, and several tissue and single cell sample preparation platforms.

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, including natural history, disease complications, and response to therapies (Collaborators: VEOIBD & SHARE Consortia)
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 (IIBDGC)

Co-Investigators

Stephan Targan, MD

Distinguished Professor, Medicine, Cedars-Sinai | Executive Director, F. Widjaja Foundation Inflammatory Bowel Disease Institute, Cedars-Sinai | Director, Inflammatory Bowel Disease (IBD) Center, Cedars-Sinai | Feintech Family Chair in Inflammatory Bowel Disease, Cedars-Sinai

Dr. Targan bases his translational and basic research programs on an integrated science paradigm. His programs focus primarily on immunopathologic mechanisms, novel therapeutics and the translation of basic science findings for use in diagnosis, prognosis and targeted therapeutic selection in inflammatory bowel disease. Human in vitro and animal model are used in genetic and immunobiologic investigations to elucidate the dysregulated immune responses in the gastrointestinal tract that lead to mucosal inflammation.

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.

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.

David Casero, PhD, MS

Director, Translational Multi'omics, Cedars-Sinai Medical Center

Dr. David Casero, PhD, develops and applies computational methods for the analyses of high-throughput multi-omics data. His lab aims to bridge the gap between traditional approaches where one type of omics data provides a snapshot into potential disease biomarkers and current multi-omics efforts that can provide information into the actual drivers of disease. The Casero Lab is particularly interested on the establishment and maintenance of normal tissue homeostasis, supported by molecular interactions between members of the tissue microenvironment (e.g., epithelial, mesenchymal and immune cells) and additional factors (e.g., signals from microbial cells). A proper understanding of these interactions is instrumental to gain insights into the etiology of some complex diseases like Inflammatory Bowel Disease and cancer.

Ivan Vujkovic-Cvijin, PhD

Assistant Professor, Divisions of Biomedical Science, Gastroenterology, and F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center

Dr. Vujkovic-Cvijin studies how microbes that inhabit the human gut contribute to immune-related diseases including inflammatory bowel disease. His work pioneered the study of gut bacteria in HIV disease progression and has helped define best practices for the investigation of gut microbial communities across human diseases. Dr. Vujkovic-Cvijin’s research group uses microbiology, immunology, ecology, and data science to carry out translational work with the end-goal of impacting human health through harnessing the host-microbiota relationship.

Esther A. Torres MD, MACP, MACG, AGAF, FAASLD

Professor, University of Puerto Rico School of Medicine

Dr. Esther A. Torres is a gastroenterologist in San Juan, Puerto Rico. She received her medical degree from University of Puerto Rico School of Medicine and has been in practice for more than 20 years. She has been a long-term collaborator with Cedars-Sinai and the NIDDK IBD Genetics Consortium, investigating IBD in the Puerto Rican population.