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

皮肤BDNF在维持皮肤机械感觉神经系统中的作用

• 批准号: 10627219
• 负责人: Cheng-Ying Ho
• 金额: $ 19.25万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10627219
• 关键词: Acetylation; Affect; Age; Amyloid beta-Protein; Animal Model; Applications Grants; Award; Axon; Biopsy; Biopsy Specimen; Brain-Derived Neurotrophic Factor; Cutaneous; Data; Deacetylase; Deacetylation; Development; Development Plans; Diabetic Neuropathies; Diabetic mouse; Discipline; Disease; Distal; Electron Microscopy; Electrophysiology (science); Environment; Fatty acid glycerol esters; Genetic Recombination; Goals; Growth Factor; Imaging Techniques; Injury; Institution; Keratin; Knockout Mice; Laboratories; Lead; Maintenance; Maryland; Measurement; Mediating; Meissners Corpuscle; Mentored Clinical Scientist Development Award (K08); Mentors; Mentorship; Methyl-CpG-Binding Protein 2; Morphology; Mus; Nerve; Nerve Fibers; Nervous system structure; Neurons; Neuropathy; Neurotrophic Tyrosine Kinase Receptor Type 2; Organ; Outcome; Pain Threshold; Pathogenesis; Pathology; Patients; Pattern; Peripheral Nervous System Diseases; Physicians; Play; Pre-Clinical Model; Preparation; Program Development; Publishing; Research; Research Personnel; Resources; Role; SIRT1 gene; Scientist; Sensory; Sensory Receptors; Skin; Tamoxifen; Testing; Therapeutic; Therapeutic Agents; Thinness; Time; Training; Training Activity; Training Programs; Universities; Work; afferent nerve; axon injury; axon regeneration; axonal degeneration; base; behavior test; career; career development; density; diabetic patient; effective therapy; experience; medical schools; mouse model; nerve supply; neuropathology; neuroprotection; nicotinamide-beta-riboside; novel; novel therapeutics; overexpression; protective effect; repaired; research and development; riboside; sensory neuropathy; sensory neuroscience; skills; success

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.

项目摘要/摘要 这份申请书描述了一个为期五年的培训计划，旨在发展学习的学术生涯 皮源性脑源性神经营养因子在维持和保护皮肤机械感觉传入中的作用。我是一个 在神经病理学方面有专长的内科科学家。我将成为一名独立的调查员 在此获奖期间，在杰出医生的指导下发展我的研究 研究人员。我的导师和我的机构的支持将有助于为 促进了我的研究和事业发展的成功。这项努力将特别涉及我的初选 导师，马里兰大学医学院的詹姆斯·罗素博士和共同导师大卫·金蒂博士 哈佛医学院和约翰·霍普金斯大学的迈克尔·波尔德基斯博士。职业发展计划 将以我在神经系统形态分析方面的强大背景为基础，增加教学培训和 具有相关学科的研究经验。我的职业目标是成为一名出色的内科医生 感觉神经系统及相关疾病领域的科学家。被指导的临床科学家 发展奖将允许我通过为实验室提供专门的时间和资源来实现这一目标 开展工作和培训活动。它还将为我提供一个机会来发展必要的技能，以 成为一名独立的研究员。在本应用程序中，我建议使用鼠标模型来研究 皮源性脑源性神经营养因子在维持TrkB表达的皮肤感觉受体中的作用及其特性 烟酰胺核苷对糖尿病神经病变保护作用的机制。这项工作 强调皮肤来源的脑源性神经营养因子在感觉神经保护中的重要性和烟酰胺的潜力 核糖苷作为治疗糖尿病神经病变的新药物。

项目成果

Cytomorphologic Features Found in Cerebrospinal Fluid Specimens of Hemophagocytic Lymphohistiocytosis Patients.

噬血细胞性淋巴组织细胞增多症患者脑脊液标本中发现的细胞形态学特征。

• DOI: 10.1093/ajcp/aqaa248
• 发表时间: 2021
• 期刊: American journal of clinical pathology
• 影响因子: 3.5
• 作者: Shyu,Susan;Luca,Dragos;VandenBussche,ChristopherJ;Ho,Cheng-Ying
• 通讯作者: Ho,Cheng-Ying

Skin keratinocyte-derived SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy.

皮肤角质细胞衍生的 SIRT1 和 BDNF 调节糖尿病神经病变小鼠模型中的机械异常性疼痛。

• DOI: 10.1101/2023.01.24.523981
• 发表时间: 2024
• 期刊: bioRxiv : the preprint server for biology
• 作者: O'Brien,Jennifer;Niehaus,Peter;Chang,Koping;Remark,Juliana;Barrett,Joy;Dasgupta,Abhishikta;Adenegan,Morayo;Salimian,Mohammad;Kevas,Yanni;Chandrasekaran,Krish;Kristian,Tibor;Chellappan,Rajeshwari;Rubin,Samuel;Kiemen,Ashley;Lu,C
• 通讯作者: Lu,C

MicroRNA (miR) 125b regulates cell growth and invasion in pediatric low grade glioma.

• DOI: 10.1038/s41598-018-30942-4
• 发表时间: 2018-08-21
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Yuan M;Da Silva ACAL;Arnold A;Okeke L;Ames H;Correa-Cerro LS;Vizcaino MA;Ho CY;Eberhart CG;Rodriguez FJ
• 通讯作者: Rodriguez FJ