The Microbiome and Disease

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The Microbiome and Disease

Tuesday, May 18, 2010

The New York Academy of Sciences

This meeting features prominent research scientist, Professor Jeffrey I. Gordon, Director of the Center for Genome Sciences at the Washington University School of Medicine. Dr Gordon’s research utilizes culture-independent metagenomic approaches, gnotobiotic mouse models, and cohorts of twins living in industrialized and developing countries to characterize the genomic and metabolic foundations of host-microbial relationships in the gut, and how these relationships influence our disease predispositions, most notably our nutritional status (including studies of obese and severely malnourished adults and children), and cardiovascular health. The second speaker will be Ramnik Xavier, Chief of the Gastrointestinal Unit at Massachusetts General Hospital. Dr Xavier will discuss his use of a ‘systems biology’ approach to characterize host-microbial interactions in inflammatory bowel diseases.

Agenda

Welcome and Introduction
Jennifer S. Henry, The New York Academy of Sciences, and S. Marvin Friedman, Hunter College, CUNY

The human gut microbiome: dining in with trillions of fascinating friends
Jeffrey I. Gordon, Washington University School of Medicine

Genetics, Pathways and Drivers of Inflammatory Bowel Disease
Ramnik J. Xavier, Massachusetts General Hospital

Networking reception

Speakers

Organizers

Marvin Friedman

Hunter College, CUNY

Jennifer Henry

New York Academy of Sciences

Speakers

Jeffrey I. Gordon, MD

Washington University School of Medicine

Jeffrey Gordon is the Dr. Robert J. Glaser Distinguished University Professor at Washington University School of Medicine in St. Louis. He joined the Washington University faculty after completing his clinical training in internal medicine and gastroenterology. He was Head of the Department of Molecular Biology and Pharmacology from 1991-2004 before becoming Director of a new interdepartmental Center for Genome Sciences. From 1994 to 2003, he served as director of the University’s Division of Biology and Biomedical Sciences, which oversees all PhD and MD/PhD students in the biological sciences. Gordon and his students conduct interdisciplinary studies of the genomic and metabolic foundations of mutually beneficial host-microbial relationships in the human gut. His work spans normal and genetically engineered mouse models to twins living in developing and industrialized countries. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the Institute of Medicine of the National Academies. He has served as the research mentor to more than 100 PhD, MD/PhD and post-doctoral students.

Ramnik J. Xavier, MD

Massachusetts General Hospital

Clinical gastroenterologist and molecular biologist Ramnik Xavier is the Chief of Gastroenterology at Massachusetts General Hospital, an affiliate of Harvard Medical School. The overall goal of the laboratory is to discover and understand the function of important mediators and effectors involved in innate (autophagy, phagocytosis) and adaptive (T cell activation) immunity. A second major focus of the laboratory is to understand the function of genes associated with Crohn’s disease/ulcerative colitis and risk of autoimmunity using the best available genomic, computational tools and model systems. Understanding the specific molecular mechanisms that contribute to disease phenotype will lead to rational classification of disease and holds the promise of accelerating therapeutic discovery. Recent findings in the laboratory have contributed to elucidating the role of autophagy in Crohn’s disease pathogenesis and the discovery of novel immune regulatory genes in innate and adaptive immunity. In future studies, Dr. Xavier’s team hopes to gain additional insights about the immune system in terms of the underlying cell-cell interactions and regulatory networks that define functional modules at the host cell-microbe interface in the intestinal mucosa.

Dr. Xavier completed his clinical training in internal medicine at Massachusetts General Hospital and subspecialty training in gastroenterology and hepatology at Massachusetts General Hospital. His laboratory is located at the Center for Computational and Integrative Biology at Massachusetts General Hospital. Dr. Xavier is the Kurt Isselbacher Associate Professor of Medicine at Harvard Medical School, an Associate Member of the Broad Institute at MIT and Harvard, and sees patients at the Crohn’s and Colitis Center at Massachusetts General Hospital where he focuses on caring for patients with Crohn’s disease and ulcerative colitis.

Abstracts

The human gut microbiome: dining in with trillions of fascinating friends

Jeffrey I. Gordon, MD, Washington University School of Medicine

Mutually beneficial relationships between microbes and animals are a pervasive feature of life on our microbe-dominated planet. We are no exception: the total number of microbes that colonize our body surfaces exceeds our total number of somatic and germ cells by 10-fold. The vast majority of our symbionts reside in our intestines where they provide us with traits we have not had to evolve on our own. In this sense, we should view ourselves as a composite of microbial and human cells, our genetic landscape as a summation of the genes embedded in our own human genome and in the collective genomes of our body habitat-associated microbial communities (‘microbiome’), and our metabolic features as an amalgamation of human and microbial attributes. We are interested in the following questions: What are the genomic and metabolic foundations of our mutually beneficial relationships with gut microbes? How do we acquire our gut microbial community (microbiota) and its microbiome? How is the human gut microbiome evolving as a function of our changing diets and lifestyles, and how does it contribute to our health, our physiological variations, and our predispositions to various diseases? How can we intentionally manipulate the functional properties of our gut microbial communities to optimize their benefit in the context of an individual host, or a population?

To address these questions, we are sequencing the genomes of representative members of the human gut microbiota so that we can make predictions about what attributes they possess, and what contributions they make to their microbial communities and hosts. We use germ-free normal and genetically engineered mice, colonized with defined collections of sequenced wild type or mutant microbial species that normally reside in the human gut, or with intact human gut communities, to simultaneously monitor host and microbial responses to colonization. We are taking the methods and insights we glean from our ‘humanized’ mouse models and applying them to mono- and dizygotic twins and their family members. Since nutritional status is such an important determinant of human health, a major issue we are addressing is the interrelationship between diet and gut microbial community structure/function, and whether differences in our gut microbial ecology affect our pre-disposition to obesity or malnutrition.

Genetics, Pathways and Drivers of Inflammatory Bowel Disease

Ramnik J. Xavier, MD, Massachusetts General Hospital

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, debilitating, inflammatory diseases of the gastrointestinal tract, collectively known as Inflammatory Bowel Diseases (IBD). Prevalence of each disorder in Western populations average 100-200/100,000. Peak incidence is in early adult life, although any age can be affected. Cumulative evidence from humans and animals studies suggests that a key factor in the pathogenesis of IBD is the disruption of intestinal homeostasis that leads to inappropriate inflammatory responses against commensal enteric flora. The gut flora is both complex and labile; it can be altered by both host genetic factors and by more transient pressures, such as inflammation. We are interested in the interplay of the IBD-susceptible host and the gut flora, both prior to and during development of disease. How do the genetic polymorphisms associated with IBD alter flora composition, both prior to disease onset and during ongoing inflammatory responses? To explore this question we are first identifying roles for IBD susceptibility loci and placing these candidates into pathways using high-throughput cell biology and genomics. To date genome wide association studies (GWAS) have identified IBD susceptibility loci in autophagy, microbe sensing and clearance, as well as drivers of intestinal immunity and adaptive responses. Once we have confirmed biological roles for candidate genes and pathways, we propose to develop novel therapeutics to target, and overcome, the identified defects and thus the associated inborn susceptibility to IBD.

Travel & Lodging

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