REGULATION OF T CELL SKIN SPECIFIC HOMING VIA PSGL1

这个指导临床科学家发展奖的建议概述了罗伯特C职业发展计划。富尔布里吉医学博士，博士旨在促进他从博士后实习生到独立研究者的发展。 强有力的证据支持候选人的潜力，建立一个成功的职业生涯的研究。 职业发展计划充分利用了候选人的优势，以及哈佛医学院环境中的个人和机构项目。 该计划将为持续的个人发展，以及学术推广和未来的资金申请提供基础。 该研究计划包括建立在候选人的免疫学培训和调查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的和重要的方面。 建立在初步发现的坚实基础上，该提案的重点是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节。 该研究计划采用标准和新的分析方法来测试有关PSGL-1的功能元件的物理排列和调节翻译后修饰的潜在机制的假设。特别注意的是集中在这些修改的作用，在指导与血管选择素的相互作用。 为研究皮肤归巢行为而开发的技术和概念将被应用于检查白细胞归巢到与炎症性疾病有关的其他组织。 因此，这份申请是一份全面的职业发展计划和研究建议，适合于推动这位年轻研究员的职业发展。

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.