department of developmental biology

Dr. Robert J. Glaser Distinguished University Professor
Director of Center for Genome Sciences

Molecular Microbiology and Microbial Pathogenesis Program
Developmental Biology Program
Molecular Cell Biology Program

Research Interests

Symbiotic relationships between bacteria and eukaryotes are a dominant theme of life on Earth. The total number of bacteria that colonize our body surfaces is estimated to exceed our total number of somatic and germ cells by an order of magnitude. Thus, a transcendent genetic view of our species should include the genes in our own genome and in the genomes of our microbial partners (the ‘microbiome’). The majority of our bacterial symbionts reside in our intestine where they provide metabolic traits that we lack. Members of our gut microbiota have endured a stringent selection to become ‘master physiologic chemists’: i.e., they have developed chemical strategies for regulating host gene expression in ways that benefit themselves and us. Identifying these host genes and the microbial effectors of their expression/function should provide new molecular targets (and new therapeutic strategies) for preventing or treating a variety of infectious and non-infectious diseases in susceptible hosts. To identify the molecular foundations of these symbiotic relationships, we use germ-free model organisms (normal and genetically engineered mice, zebrafish), colonized with genetically manipulatable bacterial species that normally reside in the human gut. We employ an array of methods ranging from functional genomics to proteomics and metabolomics to monitor host and microbial responses to colonization. We have sequenced the entire 6.3 Mb genome of a prominent member of our distal intestinal microbial community, Bacteroides thetaiotaomicron, to help decipher the strategies it uses to function as a symbiont. We have found that this organism regulates expression of genes involved in essential intestinal functions (innate immunity/mucosal barrier, nutrient processing, angiogenesis and other features postnatal gut development). The roles of specified bacterial and host genes in establishing and maintaining this symbiosis are being analyzed through genetic and biochemical tests that are guided in part by in silico reconstructions of bacterial physiology, ex vivo chemostat studies of its responses to environmental change, and genome sequencing projects involving other members of the Bacteroides genus, and another prominently represented genus (Eubacteria).

We also employ germ-free normal and transgenic mice to identify host and microbial factors that allow Helicobacter pylori, a bacterium that colonizes the stomachs of 50% of humans, to operate along the continuum between mutualism and parasitism (ulcers, cancer). Finally, we study the features of multipotent gut stem cells. These cells fuel the rapid renewal of the GI epithelium that occurs continuously throughout life. We utilize mice with genetically engineered increases in stem cell census to retrieve these progenitors and define their molecular properties (with DNA microarrays and by sequencing normalized cDNA libraries produced from laser capture microdissected cells).

• Keywords: functional genomics, genome analysis (microbial), ecology (symbiosis, ecogenomics), computational biology, systems biology, gut development, stem cells

Gordon Laboratory Website: http://gordonlab.wustl.edu.

Gordon Biosketch

Training:

• 1973-1975 Intern & Junior Assistant Resident, Medicine, Barnes Hospital, St. Louis, MO
• 1975-1978 Research Associate, Laboratory of Biochemistry, National Cancer Institute, NIH
• 1978-1979 Senior Assistant Resident, Medicine, Barnes Hospital and Chief Medical Resident, Washington University Medical Service, John Cochran VA Hospital
• 1979-1981 Fellow in Medicine (Gastroenterology), Washington University School of Medicine
  

Academic Positions (all at Washington University):

• Asst. Prof. (1981-1984); Assoc. Prof. (1985-1987); Prof. (1987-1990) of Medicine and Biological Chemistry
• Prof. & Head, Dept. Molecular Biology & Pharmacology (1991-present)
• Dr. Robert J. Glaser Distinguished University Professor (2002-present)
  

Honors Received:

• 1973 M.D. with honors; Alpha Omega Alpha; Upjohn Achievement Award
• 1981-1984 John A. and George L. Hartford Foundation Fellowship
• 1985-1990 Established Investigatorship, American Heart Association
• 1989 Membership, Association of American Physicians
• 1990 American Federation Clinical Research Young Investigator Award
• 1990 NIDDK Young Scientist Award
• 1992 Am. Gastroenterology Association Distinguished Achievement Award
• 1992 Fellow, American Association for the Advancement of Science
• 1991-1994 Distinguished Service Teaching Awards, Wash. Univ, School of Medicine
• 1994 Marion Merrell Dow Distinguished Prize in Gastrointestinal Physiology
• 1998 Wellcome Visiting Professor in the Basic Medical Sciences
• 1999 Morton I. Grossman Distinguished Lecturer, American Gastroenterologic Association
• 2000 Outstanding Mentor Award, Graduate Student Senate, Graduate School of Arts and Sciences, Washington University
• 2001 Fellow, American Academy of Microbiology
• 2001 Elected, National Academy of Sciences
• 2002 Dr. Robert J. Glaser Distinguished University Professorship
• 2003 Janssen Sustained Achievement Award in Digestive Sciences
• 2003 Horace W. Davenport Distinguished Lectureship, American Physiological Association
• 2003 Senior Scholar Award in Global Infectious Diseases, The Ellison Medical Foundation
• 2004 Sir Arthur Hurst Lecturer, British Society of Gastroenterology

Selected Publications

Hooper L, Wong M, Thelin A, et al. Molecular analysis of commensal host-microbial relationships in the intestine. Science 2001 291:881-884.

Stappenbeck, T., Hooper,L., Gordon, J. Regulation of intestinal vasculogenesis by indigenous microbes via Paneth cells, Proc. Natl. Acad. Sci. USA 2002 99: 15451-15455.

Hooper, L., Stappenbeck, T., Hong, C., Gordon, J. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nature Immunol 2003 4: 269-273.

Xu, J., Bjursell, M., Himrod, J., et al. A genomic view of the human-Bacteroides thetaiotaomicron symbiosis. Science 2003 299: 2074-2076.

Mills, J.C., Andersson, N., Hong, C.V., Stappenbeck, T.S., Gordon, J.I. Molecular characterization of gastric stem cells and their immediate daughters. Proc. Natl. Acad. Sci. USA 2002 99: 14819-14824

Contact Information

Jeffrey I. Gordon
Department of Molecular Biology and Pharmacology
Washington University School of Medicine
Campus Box 8510
4444 Forest Park
St. Louis, MO 63108
(314) 362-7243
jgordon@wustl.edu

Laboratory Website

http://gordonlab.wustl.edu

Developmental Biology Program Website

http://molecool.wustl.edu/DevBiol/