Cedars-Sinai

IBD Genetics Research Center

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

Principal Investigator

Professor, Medicine and Biomedical Sciences

Director, Translational Research in the Inflammatory Bowel Disease Institute

Director, Precision Health, Cedars-Sinai

Website

Maria T. Abreu, MD

Co-Principal Investigator

Professor of Medicine

Professor of Microbiology and Immunology

Director, Crohn's & Colitis Center

Vice Chair of Research, Department of Medicine

Dr. Abreu is a gastroenterologist who specializes in inflammatory bowel disease (IBD). Dr. Abreu has more than 20 years of leadership experience in basic, translational and clinical research and mentoring. She was elected to the American Society for Clinical Investigation in 2010 and in 2018 to the Association of American Physicians (AAP). She was awarded the Sherman Prize for her research in IBD (https://shermanprize.org/prize-recipients/maria-t-abreu-md/). Dr. Abreu’s research laboratory has done pioneering work describing the role of innate immune signaling to drive colitis-associated cancer and some sporadic colon cancers. On the translational research side, she first described that Crohn’s disease patients with Nod2 mutations have stricturing disease. This observation is the basis of prognostic testing in Crohn's disease. Her laboratory routinely applies translational approaches using patient tissue and clinical metadata to interrogate disease response to therapeutic agents. At present, the “University of Miami IBD Center Clinical Phenotype Database and Tissue Repository” has clinically annotated biospecimens (DNA, RNA, and tissue) from over 3000 patients including one of the largest cohorts of Hispanic samples in the US. Her group has distinguished itself for focusing on the genetic and environmental factors that contribute to development of IBD in Hispanics. With the support of the NIDDK, they look forward to contributing even more to this important, understudied group of patients. Finally, her interest in the burgeoning IBD risk in Hispanic immigrants has led to diet intervention studies which use comprehensive, multi-omic approaches to study the microbiome and the effect of diet on disease state. We are excited to be part of the IBDGC family.

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
Phillip Gu, MD
Andres Yarur, MD
Puja Khanna, 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

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 pleiotropic effects between IBD and other 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 and Jacob McCauley; Esther Torres, University of Puerto Rico) ; AIRE Consortium – studying IBD Genetics in sub-Saharan Africa
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.

David Casero, PhD, MS

Director, Translational Multi'omics, F. Widjaja Inflammatory Bowel Disease Institute, and 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.

Talin Haritunians, PhD

Associate Professor, F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center

Dr. Haritunians participates in multiple IBD genomics studies, overseeing Inflammatory Bowel Disease Institute’s genetic data generation and quality control with expertise in project management of large-scale genomic datasets. Her research interests are focused on the genetics underlying IBD disease severity, sex-specific differences in risk contribution to IBD, disease complications and response to medical therapies, and ancestral origin of genetic risk in admixed minority IBD populations.

Dalin Li, PhD

Advanced Genomic Statistics

Associate Professor, F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center

Dalin Li, PhD, joined Cedars-Sinai as a research scientist in 2011. He completed his undergraduate medical training at Peking University Medical School in 2000 and received his PhD in epidemiology there in 2005. Subsequently, Li worked as a postdoctoral fellow and a postdoctoral research associate in the Division of Biostatistics at the University of Southern California. His current research interests include developing and utilizing novel statistical, bioinformatics and machine learning tools to integrate large-scale genetics and "-omics" data, using those tools to explore the underlying mechanisms in IBD and thereby developing novel predictive models and treatment targets for clinical practice.

Shishir Dube, PhD

Advanced Statistical Approaches to Imaging

Research Bioinformatician/Data Scientist, Cedars-Sinai Medical Center

Shishir Dube, PhD, completed his undergraduate and master's degrees in bioengineering at the University of Pennsylvania. In 2009, Shishir received his doctorate in biomedical engineering from UCLA. His current research interests include utilizing novel data science methods to analyze and integrate imaging with other "-omics" data to understand causal mechanisms underlying inflammatory bowel disease for advancing efforts in developing innovative predictive models and treatment targets for the clinical setting.

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