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美国国立卫生研究院使命的关键组成部分。AS 这样，PA-21-107和NOT-NS-20-107提供了补充Hear Initiative Parent的机会 3根据PA-21-107的定义，在来自不同背景的个人的额外支持下获奖。 此补充申请用于提供与此NIH任务相关的额外培训支持 5授予家长奖，UC2AR082196。该家长奖是重新加入联盟的一部分，该联盟 6试图用焦点定义不同关节和关节周围组织的感觉神经支配。 7膝和颞下颌关节(TMJ)。通过更好地理解如何不同 8个神经亚型在关节中的分布以及这些亚型如何随年龄和 9疾病，可以开发新的治疗方法来减轻慢性关节疼痛的沉重负担。在……里面 10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神经支配模式与症状性骨性关节炎的发展。我们的家长奖做到了这一点 12通过研究啮齿动物骨关节炎(OA)模型中神经支配模式的变化来实现12目标 13年龄和骨性关节炎严重程度增加，如果关节神经支配之间存在病理-疼痛关系 14和人类骨性关节炎患者的症状表现，以及神经消融技术 针对特定神经亚群的15可以用于选择性地改变关节神经支配和治疗关节 16痛。这份补充申请通过提供一个独特的职业来赞扬家长奖 17与国家卫生研究院的科学劳动力发展任务有关的发展机会，而 18还确定了关节新陈代谢和关节神经移位之间的潜在关系 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 20关节新陈代谢的局部改变(与衰老、肥胖和其他共同疾病有关)将 21影响关节神经支配和骨性关节炎疼痛和残疾的表现。例如，关节 已知新陈代谢随着年龄的增长而改变，这是通过增加线粒体功能障碍和 23氧化应激、异常自噬和巨噬细胞的代谢重编程。 类似地，高血压改变关节血管系统，从而导致灌流受损、缺氧和 25减少了对关节的营养供应。关节新陈代谢的这些局部变化可以解释 26在这些并发症和OA进展之间，可能会围绕移位关节而结合 27神经支配模式与慢性骨性关节炎疼痛和残疾的发展。因此，这部作品 28本附录中提出的将利用母公司UC2奖来解决这一知识差距， 29同时协同提供一个独特的培训机会，与NIH制定 美国30名不同的科学工作者。

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.