Diversity Supplement_Folly Patterson

项目摘要 1在美国培养一支多元化的科学队伍是NIH使命的一个关键组成部分。作为 2这样，PA-21 - 107和NOT-NS-20 - 107提供了补充HEAL倡议母公司的机会 根据PA-21 - 107中的定义，3个奖项以及来自不同背景的个人的额外支持。 4本补充应用程序用于提供与NIH使命相关的额外培训支持 5父母奖，UC2AR082196。该家长奖是RE-JOIN联盟的一部分， 6旨在定义不同关节和关节周围组织的感觉神经支配， 7例发生在膝关节和颞下颌关节（TMJ）。更好地理解了 8种神经亚型通过关节分布，以及这些亚型如何随年龄变化， 9疾病，可以开发新的疗法来减轻慢性关节疼痛的沉重负担。在 特别是，我们的团队专注于定义关节移位之间的病理-疼痛关系。 11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 12目标通过研究神经支配模式如何在啮齿动物骨关节炎（OA）模型中变化， 13年龄和OA严重程度的增加，如果关节神经支配之间存在病理-疼痛关系， 14和人类OA患者的症状表现，以及神经消融技术 靶向特定神经亚群的药物可用于选择性地改变关节神经支配和治疗关节炎。 16疼痛。这个补充申请恭维父母奖提供了一个独特的职业生涯 17个发展机会与NIH的科学劳动力发展使命有关， 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， 20关节代谢的局部改变（与衰老、肥胖和其他共病状况相关）将 21影响关节神经支配和OA疼痛和残疾的表现。例如， 已知代谢通过增加线粒体功能障碍而随年龄变化， 23氧化应激、异常自噬和巨噬细胞的代谢重编程。 24类似地，高血压改变了关节血管系统，这导致灌注受损、缺氧， 25减少了关节的营养供应。这些关节代谢的局部变化可以解释 这些合并症和OA进展之间的差异为26，可能在关节移位周围合并 27神经支配模式和慢性OA疼痛和残疾的发展。因此，工作 本补充材料中提出的28项建议将利用母公司UC2奖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， 美国30个不同的科学工作者。

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.