Developmental Center for Human Urinary Bladder Myogenic Mechanisms by Ion Channels in Health and Disease

摘要 本P20项目的目标是建立人膀胱肌源性发育中心 离子通道在健康和疾病中的作用机制(DC-HUB)侧重于平滑肌离子的作用 膀胱过度活动(OAB)的病因和相关的逼尿肌过度活动(DO)的渠道。DC-Hub中心将 总部设在田纳西大学健康科学中心(UTHSC)，并涉及药学院 和医学。拟议的研究将受益于 UTHSC校区。UTHSC拥有许多成熟的生物医学研究人员和优秀的泌尿科医生 一队。格奥尔基·V·佩特科夫博士，一位在生物化学方面接受过多学科培训的知名研究员， 生理学、药理学、电生理学和泌尿学研究将担任DC-Hub中心主任 和首席调查员。我们离子通道研究战略计划的一个主要优势使我们处于 基础泌尿学研究的前沿是我们与一批令人印象深刻的 临床科学家，包括11名教职员工和15名MD泌尿外科住院医生。罗伯特·维克，医学博士，老牌医生 UTHSC临床泌尿科医生，将协调泌尿外科团队的努力。这次合作将得到埃里克的支持 Rovner医学博士，国际知名的OAB泌尿学专家和他在医学中心的临床团队 南卡罗来纳大学(MUSC)，由7名教职员工和15名MD泌尿科住院医生组成。电压- 门控性钾离子(KV)通道和瞬时受体电位(Trp)通道在尿液中表达 膀胱。我们的中心假设是KV和Trp通道是膀胱生理的关键调节因子， 因此，它们的表达、功能或调控的变化可能导致DO/OAB。我们的团队可以定期 利用供体膀胱标本研究人类KV和Trp通道功能及相关基础 科学发现与患者的临床资料。我们将使用没有OAB的患者的膀胱组织 临床病史(对照)和OAB或尿动力学证实的DO(特发性或神经源性)AS 以及实验动物，包括DO的模型。这些在DC内进行的新的良性泌尿学研究- Hub中心将为未来建立乔治·M·奥布莱恩泌尿外科研究中心提供肥沃的土壤 加州大学洛杉矶分校的课程。DC-HUB中心将对改善医疗保健产生重大影响，潜力巨大 更好地了解OAB的病因，并提供新的治疗方法来帮助OAB的大量人群 病人。鉴于OAB/DO的流行和对新疗法的需求，这项研究具有非常重要的意义。DC- Hub Center还将建立和维护一个针对高级高中的教育充实计划 学校、本科生、专业药剂学博士和医学生，进一步促进了对 泌尿科研究界。

ABSTRACT The goal of this P20 project is to establish the Developmental Center for Human Urinary Bladder Myogenic Mechanisms by Ion Channels in Health and Disease (DC-HUB) focused on the role of smooth muscle ion channels in overactive bladder (OAB) etiology and related detrusor overactivity (DO). The DC-HUB Center will be based at the University of Tennessee Health Science Center (UTHSC) and involves the Colleges of Pharmacy and Medicine. The proposed studies will benefit from the robust clinical and basic science environments of the UTHSC campus. UTHSC has many established biomedical sciences investigators and an excellent urology team. Georgi V. Petkov, PhD, an established investigator with multidisciplinary training in biochemistry, physiology, pharmacology, electrophysiology, and urological research will serve as the DC-HUB Center Director and Principal Investigator. A major strength of our strategic program on ion channel research that puts us at the forefront of basic urological research is our conduct of this research in collaboration with an impressive cadre of clinical scientists including 11 faculty members and 15 MD urology residents. Robert Wake, MD, an established UTHSC clinical urologist, will coordinate the urology team effort. The collaboration will be supported by Eric Rovner, MD, an internationally renowned OAB urology expert and his clinical team based at the Medical University of South Carolina (MUSC), consisting of 7 faculty members and 15 MD urology residents. Voltage- gated potassium ion (KV) channels and transient receptor potential (TRP) channels are expressed in the urinary bladder. Our central hypothesis is that KV and TRP channels are key regulators of urinary bladder physiology, and therefore, changes in their expression, function, or regulation may lead to DO/OAB. Our team can regularly make use of donor bladder specimens to study KV and TRP channel function in humans and correlate basic science findings with patient clinical profiles. We will use bladder tissues both from patients without an OAB clinical history (controls) and from subjects with OAB or urodynamically proven DO (idiopathic or neurogenic) as well as experimental animals, including models of DO. These novel benign urology investigations within the DC- HUB Center will provide fertile ground for future establishment of a George M. O’Brien Urology Research Center Program at UTHSC. The DC-HUB Center will have a major impact on improving healthcare with strong potential to better understand OAB etiology and provide novel therapeutic approaches to help a large population of OAB patients. Given OAB/DO prevalence and the need for new therapies, this research is highly significant. The DC- HUB Center will also establish and maintain an Educational Enrichment Program targeting advanced high school, undergraduate, professional doctor of pharmacy, and medical students, further facilitating outreach to the urology research community.