REGULATION OF T CELL SKIN SPECIFIC HOMING VIA PSGL1

这份指导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发展为独立研究者。强有力的证据支持候选人在研究领域取得成功的潜力。职业发展计划利用候选人的优势，以及哈佛医学院环境中的个人和机构项目的优势。此计划将提供持续个人发展的基础，以及学术推广和未来的资金申请。该研究计划包括基于候选人在免疫学方面的培训和研究白细胞粘附分子生物学的经验，以探索调节T细胞归巢到特定组织的机制的新颖和重要方面。在初步研究的基础上，本研究的重点是PSGL-1的结构和功能，以及与皮肤特异性T细胞归巢行为相关的翻译后修饰的调控。本研究计划采用标准和新颖的检测方法，检验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相互作用中的作用。研究皮肤归巢行为的技术和概念将被应用于研究白细胞归巢到与炎症疾病有关的其他组织。因此，该申请代表了一个全面的职业发展计划和研究建议，适合推进这位年轻研究者的职业生涯。

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.