Associate Professor of Medicine and Genetics
Director, Inflammatory Bowel Disease Center

Research Interests:

Genetics of inflammatory bowel disease, particularly variation in interleukin 23 pathway function.

Honors:   

American Society of Clinical Investigation
Chair, Steering Committee NIDDK IBD Genetics Consortium
Genetics of Health and Disease Study Section
           
The inflammatory bowel diseases (IBD) are comprised of Crohn’s disease and ulcerative colitis. These chronic, remitting disorders are characterized by an excessive inflammatory response to intraluminal intestinal bacteria. Genome-wide association studies in Crohn’s disease have resulted in the identification of a large number of novel gene associations which implicate altered intracellular processing of bacteria, as well as multiple genes along the interleukin 23 pathway in disease pathogenesis.

Current Research:   

   
There are three major areas of research interest in the laboratory.

1) Defining genetic factors contributing to IBD development. Genome-wide association studies sample a large fraction of common variation contributing to disease, but due to linkage disequilibrium patterns, typically do not identify causal alleles and/or rare variants contributing to disease. Comparative population studies provide insight into alternative mechanisms of disease pathogenesis. In addition, consideration of locus-locus interactions may provide additional power to define altered pathways contributing to disease pathogenesis.
   
2) Genotype-phenotype mapping. We are examining the functional effects of interleukin 23 pathway polymorphisms on leukocyte responses, with a particular emphasis on IL23R, IL12B, and PTPN2 polymorphisms known to contribute to IBD. In particular, genotype-dependent altered expression and function of IL23R in naïve vs. memory T lymphocytes are being examined.
   
3) Biomarker development in IBD. The development and assessment of improved therapies in IBD will be significantly enhanced by improved biomarkers to assess disease activity based on new understanding of disease mechanisms, especially with respect to the interleukin 23 pathway.