The role of skin BDNF in the maintenance of the cutaneous mechanosensory nervous system

项目总结/摘要 本申请描述了一个为期五年的培训计划，旨在发展研究领域的学术生涯 皮肤源性BDNF在维持和保护皮肤机械感觉传入中的作用。我是一个 神经病理学方面的专家医师我会以独立调查员的身份 在此期间，通过在杰出医生的指导下发展我的研究， 研究人员我的导师和我所在机构的支持将为我创造一个特殊的环境， 促进我的研究和职业发展的成功。这项工作将特别涉及我的主要 导师，马里兰州大学医学院的詹姆斯·罗素博士和共同导师， 哈佛医学院和约翰霍普金斯大学的迈克尔·波利德夫基斯博士。职业发展计划 我将在神经系统形态学分析的基础上，增加教学训练， 相关学科的研究经验。我的总体职业目标是成为一名杰出的内科医生 感觉神经系统和相关疾病领域的科学家。指导临床科学家 发展奖将使我能够通过为实验室提供专门的时间和资源来实现这一目标 工作和培训活动。这也将为我提供一个机会，发展必要的技能， 成为一名独立的研究员。在这个应用中，我建议使用小鼠模型来研究 皮肤来源的BDNF在维持表达TrkB的皮肤感觉受体中的作用，并表征其 尼克酰胺核苷对糖尿病神经病变的保护作用。工作 强调了皮肤来源的BDNF在感觉神经保护中的重要性和烟酰胺的潜力 核糖苷作为糖尿病神经病变的新型治疗剂。

PROJECT SUMMARY/ABSTRACT This application describes a five-year training program for development of an academic career in studying the role of skin-derived BDNF in the maintenance and protection of cutaneous mechanosensory afferents. I am a physician scientist with an expertise in neuropathology. I will establish myself as an independent investigator during this award period by developing my research under the mentorship of outstanding physicians and researchers. The support from my mentors and my institution will contribute to a special environment for promoting the success of my research and career development. This effort will specifically involve my primary mentor, Dr. James Russell of University of Maryland School of Medicine, and co-mentors Dr. David Ginty of Harvard Medical School and Dr. Michael Polydefkis of Johns Hopkins University. The career development plan will build on my strong background in morphologic analysis of the nervous system, adding didactic training and research experiences in related disciplines. My overall career goal is to become an outstanding physician scientist in the field of sensory nervous system and related disorders. The Mentored Clinical Scientist Development Award will allow me to achieve this goal by providing dedicated time and resources for laboratory work and training activities. It will also provide me with an opportunity to develop the necessary skills to become an independent researcher. In this application, I propose to use mouse models to study the role of skin-derived BDNF in the maintenance of TrkB-expressing cutaneous sensory receptors and to characterize its mechanism in mediating the protective effect of Nicotinamide Riboside against diabetic neuropathy. The work highlights the importance of skin-derived BDNF in sensory nerve protection and the potential of Nicotinamide Riboside as a novel therapeutic agent for diabetic neuropathy.