This Mentored Clinical Scientist Development Award proposal outlines a career development plan for Robert C. Fuhlbrigge M.D., Ph.D. designed to promote his development from post-doctoral trainee to independent investigator. Strong evidence is presented supporting the candidate's potential to forge a successful career in research. The career development plan takes advantage of the candidate's strengths, as well as those of the individuals and institutional programs available in and around the Harvard Medical School environment. This plan will provide a basis for continued personal development, as well as academic promotion and future funding applications. The research proposal included builds on the candidate's training in immunology and experience investigating the biology of leukocyte adhesion molecules to explore novel and important aspects of the mechanisms regulating T cell homing to specific tissues. Built on a strong base of preliminary findings, the focus of this proposal is the structure and function of PSGL-1 and regulation of post-translational modifications as they relate to skin specific T cell homing behavior. The research plan employs standard and novel assay methods to test hypotheses regarding the physical arrangement of functional elements and potential mechanisms regulating post-translational modifications of PSGL-1. Special attention is focused on the role of these modifications in directing interaction with vascular selectins. The techniques and concepts developed to study homing behavior in skin are to be applied to examine leukocyte homing to other tissues involved in inflammatory disease. This application thus represents a comprehensive career development plan and research proposal suitable to advance the career of this young investigator.
