Mechanisms of Bladder Urothelium-Nervous System Interactions in Health and Disease

描述（由申请人提供）：华盛顿大学奥布莱恩泌尿外科中心的首要目标是汇集优秀的跨学科研究团队，应用和分享他们个人独特的专业知识和才能，以解决良性泌尿系统疾病常见问题的机制基础。这些症状包括膀胱疼痛综合征、膀胱过度活动、排尿功能障碍和类似的膀胱症状，包括由尿路感染和其他损伤或影响尿路上皮的情况引起的牵涉性疼痛。将这些研究小组纳入协同U54合作中心的主题是他们在定义尿路上皮和神经系统之间关系方面的共同兴趣，重点关注细胞损伤对尿路上皮的多重影响以及这如何导致疼痛的感知。有三个项目将解决膀胱损伤和疼痛反应的不同但重叠的方面。项目1 （Mysorekar）将研究炎症信号、雌激素和衰老在小鼠尿路上皮损伤和膀胱感觉中的作用；项目2 （Jain）将重点研究小鼠模型和患者膀胱神经支配和损伤中GFL-Ret信号的分子机制和遗传学；项目3 （Gereau和Andriole）将在小鼠中使用光遗传学来绘制与膀胱损伤和治疗相关的感觉神经元，并对神经递质受体阻滞剂减轻相关患者疼痛的有效性进行临床研究。这些研究项目将由临床前模型核心（Mysorekar和Gereau）和人类研究核心（Jain和Lai）提供支持。行政核心（Andriole和Miner）将监督中心的运作和教育充实计划，该计划旨在为本科生提供进行泌尿学研究的机会，并主持演讲者向华盛顿大学泌尿学社区介绍最新的研究成果。机会池资金将支持试点和可行性研究，并将促进其他niddk支持站点的泌尿学研究人员使用储存的人类标本和临床信息。

DESCRIPTION (provided by applicant): The overarching goal of the Washington University O'Brien Urology Center is to bring together an interdisciplinary team of outstanding investigators to apply and share their individual unique expertise and talents to address the mechanistic bases for common problems in benign urological diseases. These include bladder pain syndrome, overactive bladder, voiding dysfunction, and similar bladder symptoms, including referred pain, that result from urinary tract infections and other injuries or conditions that affet the urothelium. The themes that justify bringing these research groups under the umbrella of a synergistic U54 Cooperative Center are their shared interests in defining relationships between the urothelium and the nervous system, with focus on multiple effects of cellular injury to the urothelium and how this results in the perception of pain. There are three projects that will address different but overlapping aspects of bladder injury and pain responses. Project 1 (Mysorekar) will examine the involvement of inflammatory signals, estrogen, and aging in urothelial injury and bladder sensation in mice; Project 2 (Jain) will focus on the molecular mechanisms and genetics of GFL-Ret signaling in bladder innervation and injury in mouse models and in patients; and Project 3 (Gereau and Andriole) will use optogenetics in mice to map sensory neurons relevant to bladder injury and therapy and perform a clinical study of the effectiveness of a neurotransmitter receptor blocker to attenuate pain in relevant patients. These research projects will be supported by a Preclinical Models Core (Mysorekar and Gereau) and a Human Studies Core (Jain and Lai). The Administrative Core (Andriole and Miner) will oversee the operations of the Center and the Educational Enrichment Program, which is designed to provide undergraduates with the opportunity to perform research in urology and to host speakers for informing the urology communities at WashU of the latest research findings. Opportunity Pool funds will support Pilot & Feasibility studies and will foster the use of banked human specimens and clinical information by urology researchers at other NIDDK-supported sites.