Midgett Distinguished Professor of Medicine
Professor Microbiology & Immunology
UNC Multidisciplinary Center for IBD Research and Treatment Director
Center for Gastrointestinal Biology and Disease Co-Director
Chief Medical Advisor, Crohn’s and Colitis Foundation of America
Clinical/Research Interests
Crohn's disease, ulcerative colitis, inflammatory bowel diseases (IBD), bacterial- host interactions, genetic regulation of commensal enteric bacteria.

University of North Carolina School of Medicine
Departments of medicine, Microbiology and Immunology

Our long term goals are to better define mechanisms of chronic intestinal inflammation and to identify areas for therapeutic intervention. Research in our laboratories is in the following four general areas.

Induction and perpetuation of chronic intestinal and extraintestinal inflammation by resident intestinal bacteria and their cell wall polymers:

We are exploring the hypothesis that normal luminal bacteria can induce immune-mediated chronic inflammation in the genetically susceptible host. We demonstrated that germ free (sterile) HLA-B27 transgenic rats, IL-10 knock out and IL-2 knock out mice fail to develop colitis, and that colitis develops within one week of colonization with specific pathogen free bacteria in these genetically engineered hosts. Moreover, all bacteria do not have equal capacities to induce inflammation, since Bacteroids vulgatus induces aggressive colitis in HLA-B27 transgenic rats, E. coli do not cause any inflammation and Lactobacilli is protective.

Mechanisms of genetically determined host susceptibility to bacterial products:

We demonstrated differential host genetic susceptibility to chronic inflammation in inbred rat strains using these experimental models of inflammation and are now exploring mechanisms of differential immunoregulation in these rat strains, concentrating on cytokine profiles and the kallikrein-kinin pathway.

Regulation of immunosuppressive molecules in intestinal epithelial cells:

We are investigating the in vivo regulation of intracellular IL-1 receptor antagonist (ic IL-1 RA) and the IkB/NFkB complex regulation of these molecules in epithelial cell lines. We have demonstrated altered IkBa degradation in intestinal epithelial cells and are exploring mechanisms of this delayed, incomplete degradation. Biologic importance of these inhibitors are examined by selective pharmacologic and molecular blockade and over expression of these molecules (i.e. dominant negative constructs and antisense oligonucleotides).

Performing clinical trials of novel therapeutic agents in inflammatory bowel disease patients:

We are investigating selective inhibitors such as rh IL-10 and anti-TNFa mAB in Crohn's disease patients and antibiotics and probiotic cocktails in ulcerative colitis patients.