REGULATION OF T CELL SKIN SPECIFIC HOMING VIA PSGL1

这份有指导的临床科学家发展奖提案概述了Robert C.Fuhlbrigge医学博士的职业发展计划，旨在促进他从博士后实习生到独立调查员的发展。提供了强有力的证据支持候选人在研究领域打造成功职业生涯的潜力。职业发展计划利用了候选人的长处，以及哈佛医学院环境中和周围的个人和机构项目的长处。这项计划将为持续的个人发展以及学术晋升和未来的资金申请提供基础。研究建议包括建立在候选人的免疫学培训和研究白细胞黏附分子生物学的经验的基础上，探索调节T细胞归巢到特定组织的机制的新的和重要的方面。建立在强大的初步发现的基础上，这项建议的重点是PSGL-1的结构和功能以及翻译后修饰的调节，因为它们与皮肤特异性T细胞归巢行为有关。该研究计划使用标准和新的分析方法来测试关于功能元件的物理排列和调节PSGL-1翻译后修饰的潜在机制的假设。特别关注这些修饰在指导与血管选择素相互作用中的作用。为研究皮肤归巢行为而开发的技术和概念将被用于检查白细胞归巢到其他与炎症性疾病有关的组织。因此，这份申请代表了一项全面的职业发展计划和研究建议，适合促进这名年轻调查员的职业生涯。

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.