Precision Immunology Institute

Inflammatory Bowel Disease

Mount Sinai and inflammatory bowel disease (IBD) have been synonymous since 1932 when the initial description of Crohn’s disease was made at The Mount Sinai Hospital. There is a strong base of clinical research, basic research, and probably one of the largest patient populations in the world. This access to patients allows us to perform unique studies looking at the control of mucosal inflammation (Colombel, Lira, Merad, Mehandru, and Cerutti), lymphocyte/ epithelial cell interactions (Berin and Lira), and the microbiome (Lira, Colombel, Faith, Clemente, Furtado, Merad, Alexandropoulos, and Cerutti).

Our investigators study the ontogeny and composition of mucosal immune cell populations (Merad, Alexandropoulos, and Mehandru), cellular migration (Lira, Furtado, and Mehandru), signaling (Ting, Chen and Xiong), apoptosis, and necrosis (Ting). In the area of immunoregulation, we study the function of specific activating or regulatory pathways (Lira and Xiong), role of complement in T cell function (Heeger) and the role of microRNAs in immune cell function (Brown).

Investigators with a major focus in IBD include:

Konstantina Alexandropoulos, PhD is an Associate Professor of Medicine at the Department of Medicine/Division of Clinical Immunology at the Icahn School of Medicine at Mount Sinai and head of the T cell-mediated Autoimmunity and Inflammation Laboratory. Research in the laboratory is focused on understanding the process of T cell tolerance and how disturbances in this process results in T cell-mediated autoimmune diseases such as inflammatory bowel disease and autoimmune hepatitis. The laboratory has uncovered mechanisms that regulate central T cell tolerance through the elimination of self-reactive T cells in the thymus, as well as peripheral tolerance that regulate self-reactivity in peripheral organs. Other research projects in the laboratory focus on elucidating T cell development/activation and leukocyte trafficking under physiologic and disease conditions.

Area(s) of Focus:
Autoimmunity
Inflammatory Bowel Disease
Vascular Inflammatory Diseases

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Judy H. Cho, MD is the Ward-Coleman Professor of Translational Genetics and Medicine and is Director of the Charles Bronfman Institute for Personalized Medicine (CBIPM). She is an international authority on inflammatory bowel disease (IBD) genetics and disease mechanisms and is leading efforts in developing novel translational approaches to study IBD. Dr. Cho has led efforts in the identification of over 200 genetic regions associated to IBD. These associations implicate a key role for IL-23 responsive CD4+ T cells in both Crohn’s disease and ulcerative colitis. Crohn’s specific genetic loci implicate inflammatory monocytes, and a major area of interest is defining tissue-based phenotypes through single cell analyses. Since 2015, Dr. Cho has led the CBIPM, which includes the School’s major biobank, named BioMe. This biobank includes DNA, plasma samples, and matched medical record information on over 39,000 Mount Sinai Health System patient volunteers. She has delivered multiple named lectureships and was awarded the Lifetime Achievement Award in Basic Science from the Crohn’s and Colitis Foundation in 2014.

Area(s) of Focus:
Inflammatory Bowel Disease  

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Jose C. Clemente, PhD is an Assistant Professor of Genetics & Genomic Sciences and Immunology and member of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai. Dr. Clemente's laboratory studies the human microbiome and its effect on human diseases. His laboratory has made critical findings in characterizing the microbiome of human populations and in understanding how deviations from microbial homeostasis is associated with immune disorders. Dr. Clemente's laboratory has also pioneered studies on how to modify the microbiome, both in early life and in adulthood, in order to restore homeostasis. He is an Associate Editor of Microbiome and mBio, and has published over 70 articles in high profile journals.

Area(s) of Focus:
Allergy
Inflammatory Bowel Disease 
Microbiome and Host Pathogen Interaction 

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Jean-Frédéric Colombel MD, PhD is a Professor of Gastroenterology and the Director of the Susan and Leonard Feinstein IBD Clinical Center and the Leona and Harry B. Helmsley Charitable Trust IBD Center at Icahn School of Medicine at Mount Sinai. He was formerly Professor of Medicine and Head of the Department of Gastroenterology at CHU Lille in France, President of the GETAID (Groupe d’Etudes Therapeutiques des Affections Inflammatoires Digestives), President of ECCO (the European Crohn’s and Colitis Organisation) and Chair of IOIBD (the International Organization for the Study of Inflammatory Bowel Disease). He has contributed to major discoveries in the field of IBD including the identification of NOD2 as a susceptibility gene for Crohn’s disease (CD), the development of the ASCA test (anti-S. cerevisiae (mannan) antibodies) which is still the most sensitive and specific serologic marker for CD and the identification of a new pathovar of Escherichia coli (AIEC for adhesive invasive E.coli) associated with ileal CD. He has been involved in most pivotal clinical therapeutic trials of the last 20 years that have helped to develop new drugs especially biologics and to improve therapeutic strategies in IBD. He is the author or co-author of more than 780 peer-reviewed articles and book chapters and is Associate Editor of Gastroenterology.

Area(s) of Focus:
Inflammatory Bowel Disease

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Jeremiah Faith, PhD received his PhD in Bioinformatics and Systems Biology from Boston University. He did his postdoctoral training in the laboratory of Jeffrey Gordon at Washington University in St. Louis Medical School with a focus on the structure and function of the gut microbiome in healthy individuals. He is currently an Assistant Professor in the Immunology Institute and the Institute for Genomics and Multiscale Biology in the Icahn School of Medicine at Mount Sinai in New York. He is also director of the Icahn School of Medicine at Mount Sinai’s Gnotobiotic Facility and co-director of the Immunology Training Area. Dr. Faith’s lab studies the interactions between diet, gut microbes, and host physiology with an emphasis on Inflammatory Bowel Disease.

Ongoing research in the lab includes:

  • Quantifying the influence of diet and the gut microbiota on host health and disease.
  • Understanding the impact of interpersonal variation in gut microbiome composition on host phenotypic variation.
  • Optimizing the engraftment of live bacterial therapeutics.
  • Tracking the stability and transmission of the human gut microbiota. 

Area(s) of Focus:
Inflammatory Bowel Disease
Cancer Immunology
Microbiome and Host Pathogen Interaction

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Dr. Emilie K. Grasset earned her PhD in Immunology at Karolinska Institutet, where she gained expertise on extrinsic and intrinsic regulation of B cells in autoimmunity and atherosclerosis. Through the projects Dr. Grasset led, her eyes were opened to the world at the intersection of the immune system and metabolism, namely that of immunometabolism, a novel cross-disciplinary field rapidly gaining traction. For her postdoctoral training, she therefore joined Dr. Cerutti’s lab, as projects ongoing in his lab were investigating the immune system in the intestinal tract, the site of interplay between nutrients, bacterial metabolites and the immune system.

Having gained expertise on how B cell responses contribute to homeostasis between the microbiota and the immune system in the gut, Dr. Grasset is now pursuing her own line of investigation with the following hypothesis: mesenteric adipose tissue is crucial for gut B cell function and gut homeostasis. Gut homeostasis is crucial to prevent inflammatory bowel disease, the incidence and prevalence of which has been steadily increasing over time worldwide.

Area(s) of Focus:
Inflammatory Bowel Disease

Peter Heeger, MD is a Professor of Medicine and Immunology. His research lab is funded through NIH R01, R21, P01, U01, and T32 grants to perform research in solid organ transplant science and studies basic mechanisms a) linking complement to T and B cell immunity and cell death and b) new approaches to inducing graft tolerance including via modulating erythropoietin receptor signaling. Additional translational studies identify and test biomarkers of acute kidney transplant injury, and test the impact and mechanisms of anti-TNF induction therapy on late kidney allograft function through an NIH-funded, randomized, controlled, multicenter, and  international trial. Transplant research is supported by the Translational Transplant Research Center (P. Heeger, Director), with its good laboratory practice-compliant immune monitoring core, common flow cytometry and sorting equipment for mechanistic studies, a microsurgery core facility that performs transplants in mice, and a T32 training grant for postdocs in transplantation science. Collaborative clinical trials are performed within the Recanati Miller Transplant Institute (S. Florman, Director). Inquiries regarding open faculty positions in transplant science should be sent to peter.heeger@mssm.edu.

Area(s) of Focus:
Transplant 

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Dr. Sergio Lira received his MD from the Universidade Federal de Pernambuco in Brazil (1982) and his PhD in Physiology and Pharmacology from the University of California at San Diego (1988). He did his postdoctoral training at the Roche Institute for Molecular Biology in Nutley, NJ. After his postdoctoral training he worked for 11 years in the pharma sector, first at Bristol-Myers Squibb (1992-1996) and then at Schering-Plough (1996-2002). Dr Lira joined Mount Sinai in 2002 as the Irene Diamond Associate Professor of Immunology. In 2007 he became the co-Director of the Immunology Institute (with Dr. Lloyd Mayer), and in 2013 was promoted to Director, a position he occupied until 2016. He is currently The Leona M. and Harry B. Hemsley Charitable Trust Professor of Immunology. His research focuses on the role of immune cells and the microbiome in mucosal inflammation and cancer. He has organized international meetings in this field, including the 2003 Keystone Symposium on Chemokines and the 2006 Gordon Research Conference on Chemotactic Cytokines. He was elected to the Henry Kunkel Society in 2006 and to the Association of American Physicians in 2008. Dr. Lira was a Visiting Professor at the Southern Medical University in Guangzhou, China (2013-2016) and is a member of the Board of Scientific Counselors of the National Cancer Institute (2013-present).

Area(s) of Focus:
Inflammatory Bowel Disease
Autoimmunity
Cancer Immunology
Microbiome
Skin Inflammatory Disease

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Miriam Merad, MD, PhD is the Icahn School of Medicine at Mount Sinai Chair Professor in Cancer Immunology and the Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai in New York. Dr. Merad obtained her MD at the University of Algiers, Algeria. She did her residency in Hematology and Oncology in Paris, France and obtained her PhD in immunology in collaboration between Stanford University and University of Paris VII. She was recruited to the Icahn School of Medicine at Mount Sinai in 2004 and was promoted to the rank of Associate Professor with Tenure in 2007 and to Full Professor in 2010 and in 2014, she obtained an Endowed Chair Professor in Cancer Immunology.

Dr. Merad’s laboratory studies the contribution of macrophages and dendritic cells to Cancer and Inflammatory disease in mice and Human. Dr. Merad’s pioneering work mapping the regulatory network of dendritic cells (DCs) resulted in identification of a lineage of DC, the CD103+ DC, that is now considered a key target to improve antiviral and antitumor immunity. Another of her key discoveries is that, contrary to the previously-held beliefs that monocytes are precursors of macrophages, she found that tissue-resident macrophages in fact arise from embryonic precursors that take residence in tissues prior to birth and are maintained independently of adult hematopoiesis. These insights are now being used to develop novel macrophage and dendritic cell-specific targets for the treatment of Cancer and Inflammatory diseases. 

Dr. Merad has authored more than 160 primary papers and reviews in high profile journals. Dr. Merad receives generous funding from the National Institutes of Health (NIH) for her research on innate immunity and their contribution to human disease, and belongs to several NIH consortia. She is an elected member of the American Society of Clinical Investigation and lectures around the world on her work. 

Area(s) of Focus:
Cancer Immunology
Inflammatory Bowel Disease
Neuroimmunology 

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Adrian Ting, PhD is an Associate Professor of Medicine/Immunology. His lab studies how ubiquitination affects cellular survival and death, as well as inflammatory signaling pathways. The lab discovered that non-degradative K63-linked polyubiquitination of the signaling molecule RIPK1, or the lack thereof, determines whether cell survival or cell death ensues in response to TNF. Ubiquitination of RIPK1 serves to function as an early cell death checkpoint in TNF signaling and blocking this process leads to apoptosis and necroptosis. Central to converting RIPK1 to a death-signaling molecule is its upstream regulator CYLD, a tumor suppressor and a deubiquitinating enzyme that preferentially removes K63-linked polyubiquitin chains from RIPK1. In recent years, the lab has shifted its focus to post-translational mechanisms (PTM) that inhibit CYLD, which has to be kept inactive to prevent inappropriate cell death. These inhibitory PTM include phosphorylation, proteolysis and degradation. Disruption of these inhibitory mechanisms led to excessive CYLD/RIPK1-mediated cell death and inflammation in multiple tissues including the skin, lung, and liver. The role of this CYLD-mediated cell death in physiological responses to microbial infections is currently under investigation. Furthermore, the role of this cell death in pathologies such as inflammatory disorders, transplantation and cancer are also under investigation. The goal of the lab is to thoroughly characterize the regulation and function of this cell death pathway so that rationally designed drugs can be developed to disrupt it for therapeutic purposes.

Area(s) of Focus:
Cancer Immunology
Immunodeficiency
Skin Inflammatory Diseases
Transplant 

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Huabao Xiong, MD, PhD is an Associate Professor of Medicine/Immunology. The Xiong lab studies the functions of Interferon Regulatory Factor 8 (IRF-8) expressed in different immune cells in the regulation of immune responses. They study the regulation of T helpers by IRF8 in the development of inflammatory bowel diseases; reprograming of macrophage polarization by IRF-8 in host defense against intracellular bacterial infection; modulation of MDSCs by IRF-8 in tumor development. They also study the functions of nitric oxide (NO) produced by T cells in the regulation of T helper cell development and the contribution of T cell-derived iNOS in the development of intestinal inflammation. The laboratory is dedicated to understanding the transcriptional regulation in the development of inflammatory bowel diseases.

The research direction includes:

  • Transcriptional regulation of Th17 cells in the development of intestinal inflammation.
  • Molecular mechanisms for the regulation of proinflammatory M1 macrophages in inflammatory diseases.
  • Identification of novel therapeutic targets for suppression of Th17 cells and M1 macrophages for the therapeutic purposes.

Area(s) of Focus:
Inflammatory Bowel Diseases 

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