Candidate/environment: He became interested in an academic career while in medical school. His senior project examining radiation treatment in Hodgkin's disease was recognized as the most outstanding original pediatric research. During residency training, his interest focused to gastroenterology, specifically the pathogenesis of inflammatory bowel disease (IBD). For this reason, he accepted a fellowship position at Children's Memorial Hospital. He examined various avenues of research, choosing Dr. Terrence Barrett, a NIH-funded mucosal immunologist, to mentor his training in intestinal immunology. Over the past 2.5 years, he has developed a sincere enthusiasm to continue his career as a physician-scientist and investigate IBD. The mentor has a strong laboratory environment for support with PhD's specializing in molecular biology, microbiology, and immunology. Dr. Stephen Miller is serving as co-mentor for this application, making available the entire resources of his lab and the resources of the Department of Immunobiology at Northwestern University. His immediate career goal is to obtain funding to protect a majority of his time to continue to develop the proposed studies in this application, facilitating intellectual development as well as novel ideas and data that can be used to generate future independent funding. This protected time will allow him to make the commitment necessary to be a successful clinician-scientist. Research: Pathways controlling T cell trafficking to the colon are essential to the pathogenesis of human IBD, but poorly understood. This proposal focuses on a pathway of effector T cell recruitment to the colon. It initially focuses on characterizing the recruitment for P-selectin glycoprotein ligand (PSGL) 1 as a T cell marker for direct effector cells to the colon. More importantly, the requirement for this pathway will be studied in an experimental model of Th1-mediated colitis (IL-10 knockout mice) and a pathogen-induced Th1-mediated model of colitis in which the pathogen has been manipulated to aloe for examination of antigen-specific recruitment. The ultimate goal is that these principles will help to understand the pathogenesis of human IBD and provide potential targets for therapy. This award will facilitate his transition to an independent research career. He has the commitment of the University and Division to transfer novel observations and data from this proposal into his into his own lab during the 4th year. During the final two years, technical and lab support will be provided to aid his generation of a proposal for independent funding.
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