Photo: Clara Abraham, MD
Clara Abraham, MD
Year elected: 2014
Current membership category: Senior
Yale University
333 Cedar St. LMP1080
New Haven, CT 06520
United States of America
Phone: 203-785-5610
Facsimile: 203-785-5673

Biographical statement

My laboratory is interested in defining the diverse and unique mechanisms contributing to intestinal immune homeostasis and the dysregulation occurring in inflammatory bowel disease (IBD). Host-microbe interactions are central to the development of IBD, with initiating innate mechanisms, particularly through pattern recognition (PRR) pathways, playing a key role. We have utilized unbiased approaches to define novel, unexpected genes that modulate PRR-responses, such as the effects of ICOSLG and TNSF15 polymorphisms in innate cells. We have further defined functional immunological consequences of other IBD-associated genetic polymorphisms in PRR pathways, including in NOD2, IRF5, IL1R/IL18R, and STAT3. Defining these altered mechanisms is a critical step in rationally prioritizing new therapeutic targets in IBD. As such, we established that the glutamine allele (Arg381Glu) in IL23R which confers protection against IBD, psoriasis and ankylosing spondylitis, is a loss-of-function allele. This indicates that down-modulating IL-23 pathway function would be beneficial, and major efforts to block this pathway in human inflammatory diseases are ongoing. We have further sought to define the pathways contributing to the unique phenotype of intestinal macrophages, in which mechanisms for clearance of microbes have been optimized in a manner that minimizes tissue injury; such a dichotomy is beneficial in the high microbial density environment of the intestine. Restoring these specialized functions in intestinal macrophages is yet another potential therapeutic approach in the cycle of intestinal inflammation observed in IBD.

Institutional affiliations

Yale School of Medicine (Primary)
Harriet Margot Kluger, MD is the representative at this institution.

Specialties

Gastroenterology
Immunology
Internal Medicine