Bladder Blood Flow and Vascular Contractility Regulate Bladder Function

 描述（由申请人提供）：本提案描述了一个5年的计划，在下尿路生理学的学术生涯的发展。候选人具有平滑肌生理学背景，并在Stephanie Watts和William杰克逊博士（密歇根州立大学）的指导下完成了药理学和毒理学博士培训。然后，他来到佛蒙特大学作为博士后研究员，开始走向独立的研究生涯的道路。现在，他结合了他在平滑肌生理学和血管药理学方面的优势，提出了一项新的建议，研究膀胱血流与糖尿病膀胱功能障碍的关系。近一半的糖尿病患者会出现下尿路症状（LUTS），这会显著降低他们的生活质量。虽然有充分的证据表明，膀胱血流受损与下尿路症状有关，但我们对膀胱血流调节及其对膀胱功能的影响的理解存在根本性的差距。 这个项目的目标是了解膀胱血管系统的独特特性如何调节膀胱功能。此外，该项目将研究血流量减少是否会导致糖尿病膀胱功能障碍，特别关注调节膀胱小动脉血管张力的信号机制。这个假设驱动的研究项目将使申请人能够发展最先进的体外和体内生理学方法的技能，包括电生理学、离体血管的直径和膜电位测量以及体内尿动力学测量，这将提供前所未有的细节糖尿病期间膀胱的血管功能。结果可能会 重新构建LUTS治疗，以包括血管和神经治疗干预。佛蒙特大学（UVM）以其在平滑肌生物学方面的实力而享誉国际，在血管和膀胱生理学方面拥有独特的专业知识。Mark纳尔逊博士将指导候选人的科学发展纳尔逊博士是血管生物学和膀胱生理学领域公认的领导者，并培养了许多博士后研究员和研究生，其中许多人现在是独立的研究人员。为了加强候选人的培训，该计划招募了一个指导委员会的专业知识，包括博士约瑟夫布雷登，乔治韦尔曼，玛格丽特维扎德和马克普兰特。Brayden博士开创了血管平滑肌膜电位研究的技术。Wellman博士增加了K+通道功能和电生理学方面的专业知识。Vizzard博士带来了膀胱研究和体内有意识膀胱测压的丰富经验。Plante博士是一位成功的临床泌尿科医生，对转化科学和研究有着独到的见解。这种研究环境最大限度地提高了候选人建立科学利基的潜力，从而可以构建学术生涯。该项目将促进候选人的持续技术、智力和专业培训，并将协助候选人在学术研究机构建立独立的研究实验室。

 DESCRIPTION (provided by applicant): This proposal describes a 5-year program for the development of an academic career in lower urinary tract physiology. The Candidate has a background in smooth muscle physiology, and completed doctoral training in Pharmacology and Toxicology under the mentorship of Drs. Stephanie Watts and William Jackson (Michigan State University). He then came to the University of Vermont as a Postdoctoral Fellow to begin a path toward an independent research career. He now combines his strengths in smooth muscle physiology and vascular pharmacology to create a novel proposal investigating bladder blood flow as it relates to bladder dysfunction in diabetes. Nearly half of all diabetic patients experience lower urinary tract symptoms (LUTS), which significantly reduce their quality of life. Although ample evidence links impaired bladder blood flow to LUTS, a fundamental gap exists in our understanding of bladder blood flow regulation and its effects on bladder function. The goals of this project are to understand how the unique properties of the urinary bladder vasculature regulate bladder function. Furthermore, this project will investigate if decreased blood flow leads to bladder dysfunction in diabetes, with a specific focus on signaling mechanisms that regulate vessel tone in bladder arterioles. This hypothesis-driven research project will allow the applicant to develop skills in state-of- the art in vitro and in vivo physioogy methods, including electrophysiology, diameter and membrane potential measurements in isolated blood vessels, and in vivo urodynamic measurements, that will provide unprecedented detail into vascular function in the urinary bladder during diabetes. The results could potentially re-frame LUTS treatment to include both vascular and neurological therapeutic interventions. The University of Vermont (UVM) is internationally recognized for its strength in smooth muscle biology, with unique expertise in both vascular and urinary bladder physiology. Mark Nelson, Ph.D. will mentor the Candidate's scientific development. Dr. Nelson is a recognized leader in the field of vascular biology and bladder physiology and has trained numerous postdoctoral fellows and graduate students, many of whom are now established independent investigators. To enhance the Candidate's training, the program enlists the expertise of a mentoring committee, including Drs. Joseph Brayden, George Wellman, Margaret Vizzard and Mark Plante. Dr. Brayden pioneered techniques for the study of vascular smooth muscle membrane potential. Dr. Wellman adds expertise in K+ channel function and electrophysiology. Dr. Vizzard brings substantial experience with bladder research and in vivo conscious cystometry. Dr. Plante is a successful clinical urologist with perspectives on translational science and research. This research environment maximizes the potential for the Candidate to establish a scientific niche from which an academic career can be constructed. This project will facilitate continued technical, intellectual, and professional training of the Candidate, and will assist the Candidate in the establishment of an independent research laboratory at an academic research institution.