THE ROLE OF LFA-1 IN T CELL ACTIVATION

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DESCRIPTION (adapted from the application) Clara Abraham, MD, received a baccalaureate degree in computer science from the College of Engineering, high honors, in 1985 at the University of Illinois, Urbana, and a medical degree in 1989 at the University of Chicago, Pritzker School of Medicine. Following internal medicine residency at Rush Presbyterian-St. Luke's Medical Center, she completed a three year basic science fellowship in gastroenterology at The University of Chicago. During this period, she entered the laboratory of Dr. Thomas A. Brasitus, and studied the role of protein kinase C and 1,25(OH)2D3 in the growth, differentiation and apoptosis of Caco-2 human colon cancer cells. Following the three year fellowship, she entered the laboratory of Dr. Jim Miller in order to pursue additional training in basic science immunology. She has been investigating the role of LFA- I in the activation of T lymphocytes for the past 3 years. In the present proposal, Dr. Abraham plans to pursue questions regarding the in vitro and in vivo role of LFA-1 in T cell function. Specifically, she intends to further understand and segregate the contributions of specific functions of LFA-I within T cell activation through in vitro mutagenesis. She will then utilize the information acquired in vitro to identify specific, dramatic T cell phenotypes to be analyzed in in vivo models of inflammation, in particular, murine models of inflammatory bowel disease. The goal of such an approach is to allow for segregation of LFA-l's contribution to T cell trafficking versus T cell activation, and assess the relative importance of these functions in vivo. As Dr. Abraham has no formal training in animal models of IBD and intestinal immunology, the proposed research career development plan requests support for five years in order to provide a formalized, comprehensive training program for her that will allow her to establish an independent laboratory to pursue research in these in vivo models of inflammation.