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障碍，也是前三名负障碍之一中风和阿尔茨海默氏病后生活质量的效应子。尽管进行了数十年的研究，但膀胱饱满度的机制仍然未知。发展和测试膀胱功能障碍的新型疗法是我们缺乏了解的机制膀胱充满感。了解这些机制是发展的基础维持和改善膀胱功能的治疗和干预措施。该项目的总体目标是了解压力敏感性的基础及其与膀胱填充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出口通过壁张力的变化；（2）在细胞外基质中没有足够的刚度，这些壁张力的变化不会发生。本质上，我们建议这是墙壁张力的变化 - 不是瞬态合同本身 - 在填充过程中驱动传入的出口。那，墙壁上的任何变化合规性将对膀胱饱满感的感觉产生重大影响。这个概念仅关注关于膀胱的机械性能，没有猜测不同细胞类型的作用参与信号本身。首先了解膀胱壁的合规性如何改变感觉，我们可以然后更深入地研究更改合规性的机制，从而改善我们的工作膀胱功能障碍的知识。具体目的是：1）确定组成和机械脱细胞外基质和完整的尿道膀胱的特性； 2）阐明膀胱壁刚度，膀胱饱满度和感官流出到中枢神经系统之间的关系。为了解决这一重要的知识差距，我们组建了一个跨学科的专家团队在生理学，细胞生物学，神经学，统计和临床泌尿外科领域，并招募了有希望的新的良性泌尿生殖器疾病的研究者Sara Roccabianca博士。 Roccabianca博士具有独特的专业知识在软生物组织机械表征，微结构定量和数学中软组织的建模。这支来自博蒙特健康和密歇根州立大学的团队，位于密歇根州泌尿外科跨学科中心彼此近似研究与教育（MI-CURE）。除了强大的良性泌尿外科研究计划 Mi-Cure创新和尖端的方法，有一个令人兴奋的教育丰富计划从高中生到医学生，培训和心理所有级别的成人学习者，以帮助扩展并增强良性泌尿外科研究。 Mi-Cure由既定的科学家 - 医师团队共同指导博士。羔羊和总理，制定了明确的沟通和协调计划。一起， Mi-Cure将促进成功的合作，教育计划和创新研究。