Diversity Supplement_Folly Patterson

多样性补充资料_Folly Patterson

• 批准号: 10841930
• 负责人: Kyle D Allen
• 金额: $ 21.75万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10841930
• 关键词: Ablation; Address; Affect; Age; Aging; Arthralgia; Autophagocytosis; Award; Chronic; Complex; Degenerative polyarthritis; Development; Disease; Fostering; Goals; Helping to End Addiction Long-term; Human; Hypertension; Hypoxia; Immune system; Impairment; Individual; Joints; Knee joint; Knowledge; Link; Macrophage; Metabolic; Metabolism; Mission; Modeling; Obesity; Oxidative Stress; Pain; Parents; Pathology; Patients; Pattern; Perfusion; Rodent; Sensory; Severities; Symptoms; Techniques; Temporomandibular Joint; Tissues; Training Support; United States National Institutes of Health; Work; Workforce Development; career; comorbidity; disability; immunoregulation; improved; mitochondrial dysfunction; nerve supply; neural; novel therapeutics; nutrition; osteoarthritis pain; sex; training opportunity

Project Summary 1 Fostering a diverse scientific workforce in the US is a key component of the NIH’s mission. As 2 such, PA-21-107 and NOT-NS-20-107 provide opportunities to supplement HEAL Initiative parent 3 awards with additional support of individuals from diverse backgrounds, as defined in PA-21-107. 4 This supplement application serves to offer additional training support related to this NIH mission 5 to parent award, UC2AR082196. This parent award is part of the RE-JOIN Consortium, which 6 seeks to define the sensory innervation of different articular and peri-articular tissues with a focus 7 on the knee and temporomandibular joint (TMJ). With an improved understanding of how different 8 neural subtypes are distributed through the joint and how these subtypes change with age and 9 disease, new therapies can be developed to reduce the heavy burden of chronic joint pain. In 10 particular, our team focuses on defining pathology-pain relationships between shifting joint 11 innervation patterns and the development of symptomatic OA. Our parent award achieves this 12 goal by investigating how innervation patterns change in rodent osteoarthritis (OA) models with 13 increasing age and OA severity, if pathology-pain relationships exist between joint innervation 14 and the presentation of symptoms in human OA patients, and whether neural ablation techniques 15 targeted at specific neural subsets can be used to selectively alter joint innervation and treat joint 16 pain. This supplement application compliments the parent award by offering a unique career 17 development opportunity related to the NIH’s mission for scientific workforce development, while 18 also identifying potential relationships between joint metabolism and shifting joint innervation 19 patterns. Because many metabolites are neuroactive and/or immunomodulatory, it is likely that 20 local alterations in joint metabolism (related to aging, obesity, and other co-morbid conditions) will 21 affect joint innervation and the presentation of OA pain and disability. For example, joint 22 metabolism is known to change with age through increased mitochondrial dysfunction and 23 oxidative stress, abnormal autophagy, and the metabolic reprogramming of macrophages. 24 Similarly, hypertension alters joint vasculature, which results in impaired perfusion, hypoxia, and 25 reduced nutrition supply to the joint. These local shifts in joint metabolism could explain links 26 between these comorbidities and OA progression, which could coalesce around shifting joint 27 innervation patterns and the development of chronic OA pain and disability. As such, the work 28 proposed in this supplement will leverage the parent UC2 award to address this gap in knowledge, 29 while synergistically providing a unique training opportunity related to NIH’s mission to develop a 30 diverse scientific workforce in the US.

项目概要 1 在美国培养多元化的科学人才是 NIH 使命的重要组成部分。 2 个这样的 PA-21-107 和 NOT-NS-20-107 提供了补充 HEAL Initiative 家长的机会 3 个奖项，并得到来自不同背景的个人的额外支持（如 PA-21-107 中的定义）。 4 此补充应用程序旨在提供与此 NIH 任务相关的额外培训支持 5 家长奖，UC2AR082196 该家长奖是 RE-JOIN 联盟的一部分。 6 试图定义不同关节和关节周围组织的感觉神经支配，重点是 7 对膝关节和颞下颌关节 (TMJ) 有何不同有了更深入的了解。 8 种神经亚型分布在关节中，以及这些亚型如何随年龄和年龄而变化 9种疾病，可以开发新的疗法来减轻慢性关节疼痛的沉重负担。 10 特别是，我们的团队专注于定义移动关节之间的病理-疼痛关系 11 种神经支配模式和症状性 OA 的发展我们的家长奖实现了这一点。 通过研究啮齿类骨关节炎 (OA) 模型的神经支配模式如何变化来实现 12 个目标 13 如果关节神经支配之间存在病理-疼痛关系，年龄和 OA 严重程度都会增加 14 人类 OA 患者的症状表现，以及是否需要神经消融技术 15 针对特定神经子集可用于选择性改变关节神经支配并治疗关节 16 痛苦 该补充申请通过提供独特的职业来补充家长奖。 17 与 NIH 科学劳动力发展使命相关的发展机会，同时 18 还确定了关节代谢和关节神经支配变化之间的潜在关系 19 种模式由于许多代谢物具有神经活性和/或免疫调节作用，因此很可能是这样的。 关节代谢的 20 种局部改变（与衰老、肥胖和其他共病相关）将 21 影响关节神经支配以及 OA 疼痛和残疾的表现。 22 众所周知，新陈代谢会随着线粒体功能障碍的增加而发生变化， 23 氧化应激、异常自噬和巨噬细胞的代谢重编程。 24 同样，高血压会改变关节脉管系统，从而导致灌注受损、缺氧和 25 关节营养供应减少可以解释关节代谢的这些局部变化。 26 这些合并症与 OA 进展之间可能会围绕移位关节合并 27 神经支配模式与慢性 OA 疼痛和残疾的发展 因此，这项工作。 本补充中提出的 28 将利用母公司 UC2 奖项来解决这一知识差距， 29 同时协同提供与 NIH 的使命相关的独特培训机会，以开发 美国有 30 名多元化的科学工作者。