MI-CURE Research Project

MI-CURE研究项目

基本信息

批准号：
10491230
负责人：
Sara Roccabianca
金额：
$ 12.03万
依托单位：
WILLIAM BEAUMONT HOSPITAL RESEARCH INST
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-22 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10491230
关键词：
Address Adult Affect Alzheimer&apos s Disease Animal Model Applications Grants Attention Benign Biological Bladder Bladder Diseases Bladder Dysfunction Cells Cellular biology Clinical Collaborations Communication Data Education Elasticity Elements Esthesia Event Extracellular Matrix Feeling Fibrosis Fostering Future Goals Health High School Student Histology Hypertrophy Image Immunofluorescence Immunologic Impairment Individual Institution Intervention Knowledge Lead Link Lower urinary tract Measurement Mechanics Medical Students Mentors Methods Michigan Muscle Muscle Cells Muscle Tonus Nerve Neuraxis Organ Overactive Bladder Physicians Physiological Physiology Quality of life Research Research Personnel Research Project Grants Rodent Model Role Scientist Sensory Signal Transduction Smooth Muscle Smooth Muscle Myocytes Speed Stress Structure System Talents Techniques Testing Tissues Training Universities Urine Urogenital Diseases Urologic Diseases Urology afferent nerve cell type clinical care data infrastructure diabetic education research experimental study improved innovation intravesical mathematical model mechanical properties non-diabetic novel novel therapeutics post stroke pressure programs recruit soft tissue statistics urologic

项目摘要

ABSTRACT Bladder dysfunction is the costliest lower urinary tract disorder and one of the top three negative effectors on quality-of-life after stroke and Alzheimer’s Disease. Despite decades of research, the mechanisms by which bladder fullness is sensed are still unknown. A major barrier to developing and testing novel therapies for bladder dysfunction is our lack of understanding the mechanism of how bladder fullness is sensed. Understanding these mechanisms is fundamental to develop improved therpautics and interventions to maintain and improve bladder function. The overall goal of this project is to understand the basis of pressure sensing and its linkage to afferent nerve activation during bladder filling. We propose the novel overarching concept that: (1) localized bladder wall contractions drive afferent outflow through changes in wall tension; and (2) without sufficient stiffness in the extracellular matrix, these changes in wall tension cannot occur. In essence, we propose that it is the changes in wall tension – not the transient contraction itself – that drive afferent outflow during filling. Thus, any change in wall compliance would have significant effects on the sensation of bladder fullness. This concept focuses solely on the mechanical properties of the bladder, without speculation as to the role(s) of different cell types involved in the signaling itself. By first understanding how bladder wall compliance alters sensation, we can then delve deeper into the mechanisms by which compliance is changed, thereby improving our working knowledge of bladder dysfunction. The specific aims are: 1) Determine the composition and mechanical properties of both the decellularized extracellular matrix and the intact urinary bladder; and 2) Elucidate the relationship between bladder wall stiffness, bladder fullness, and sensory outflow to the CNS. To address this significant knowledge gap, we have assembled an interdisciplinary team of experts in physiology, cell biology, neurourology, statistics, and clinical urology and have recruited a promising new investigator to benign genitourinary disease, Dr. Sara Roccabianca. Dr. Roccabianca has unique expertise in soft biological tissue mechanical characterization, microstructural quantification, and mathematical modeling of soft tissues. This assembled team from Beaumont Health and Michigan State University, located in close proximity to each other, form the Michigan Interdisciplinary Center for Urologic Research and Education (MI-CURE). In addition to the strong benign urology research program using innovatice and cutting-edge approaches, MI-CURE has an exciting Educational Enrichment Program to train and mentor all levels of adult learners, from high school students to medical students, to help expand and enhance benign urology research. MI-CURE is co-directed by the established scientist-physician team of Drs. Lamb and Chancellor, with clear communication and coordination plans in place. Together, MI-CURE will foster successful collaborations, education initiaives, and innovative research.

抽象的膀胱功能障碍是最昂贵的下尿路疾病，也是三大负面疾病之一尽管经过数十年的研究，中风和阿尔茨海默病后生活质量的影响因素。感知膀胱充盈的机制仍不清楚，这是发育和发育的主要障碍。测试膀胱功能障碍的新疗法是我们缺乏对膀胱功能障碍机制的了解如何感知膀胱充盈度是改善膀胱充盈度的基础。该项目的总体目标是维持和改善膀胱功能的治疗和干预措施。了解压力传感的基础及其与膀胱充盈过程中传入神经激活的联系。我们提出了一个新颖的总体概念：（1）局部膀胱壁收缩驱动传入神经通过改变壁张力而流出；(2) 细胞外基质没有足够的硬度，这些本质上，我们认为壁张力不会发生变化，而不是壁张力的变化。短暂的收缩本身——在充盈过程中驱动传入流出，因此，壁的任何变化。顺应性会对膀胱充盈感产生显着影响。这个概念仅关注于膀胱充盈感。膀胱的机械特性，而不推测不同细胞类型的作用通过首先了解膀胱壁顺应性如何改变感觉，我们可以然后更深入地研究合规性改变的机制，从而改善我们的工作了解膀胱功能障碍的具体目标是： 1) 确定其成分和机械结构。脱细胞细胞外基质和完整膀胱的特性；2) 阐明膀胱壁硬度、膀胱充盈度和中枢神经系统感觉流出之间的关系。为了解决这一重大知识差距，我们组建了一个跨学科专家团队在生理学、细胞生物学、神经泌尿学、统计学和临床泌尿学领域，并招募了一批有前途的新人 Sara Roccabianca 博士是良性泌尿生殖系统疾病的研究者，拥有独特的专业知识。软生物组织机械表征、微观结构量化和数学该团队来自博蒙特健康中心和密歇根州立大学，彼此靠近，形成密歇根泌尿科跨学科中心研究和教育（MI-CURE）除了使用强大的良性泌尿学研究计划。 MI-CURE 采用创新和前沿的方法，拥有令人兴奋的教育强化计划培训和指导从高中生到医学生的各个级别的成人学习者，以帮助扩展并加强良性泌尿外科研究。 MI-CURE 由已建立的科学家-医生团队共同指导。兰姆博士和校长一起制定了明确的沟通和协调计划， MI-CURE 将促进成功的合作、教育举措和创新研究。