Molecular and neuro-inflammatory biology of aging bladder in normal and disease states

正常和疾病状态下老化膀胱的分子和神经炎症生物学

• 批准号: 9789177
• 负责人: Indira U Mysorekar
• 金额: $ 30.07万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789177
• 关键词: Affect; Age; Aging; Area; Automobile Driving; Basic Science; Benign; Biology; Biology of Aging; Bladder; Bladder Diseases; Bladder mucosa; Chronic; Clinical; Collaborations; Collection; Communities; Cystitis; Cystoscopy; Discipline; Discipline of obstetrics; Disease; Disease model; Educational Activities; Ensure; Fellowship; Female; Fostering; Foundations; Functional disorder; Future; Goals; Grant; Gynecology; Health; High School Student; Human; Immune System Diseases; Immunologics; Immunology; Individual; Infection; Infective cystitis; Inflammation; Infrastructure; Institution; Interdisciplinary Study; Kidney; Knowledge; Laboratories; Link; Lower urinary tract; Lymphocyte; Lymphocytic Infiltrate; Medical Students; Medicine; Molecular; Mus; Neurobiology; Pain; Pathologist; Pathology; Patients; Pelvis; Physicians; Postmenopause; Process; Reconstructive Surgical Procedures; Recording of previous events; Recurrence; Research; Research Activity; Research Personnel; Research Project Grants; Resources; Sampling; Scientist; Specimen; Students; Submucosa; Talents; Testing; Training; Training Programs; Translational Research; Translations; United States National Institutes of Health; Universities; Urge Incontinence; Urinary tract infection; Urination; Urologic Diseases; Urology; Visit; Washington; Woman; Work; aged; base; design; experience; high school; human old age (65+); innovation; interdisciplinary approach; interest; knowledge base; lower urinary tract symptoms; medical schools; micturition urgency; mouse model; multidisciplinary; neuroinflammation; next generation; novel marker; pre-clinical; prevent; programs; recruit; repository; summer research; translational scientist; treatment optimization; treatment strategy; undergraduate student; university student; urologic

PROJECT SUMMARY Nearly 50% of post-menopausal women suffer from urinary tract infections (UTIs), and over 25% of post- menopausal women experience burdensome lower urinary tract symptoms (LUTS), including urinary urgency, incontinence, and painful urination. Given that nearly 1.5 billion people will be ≥65 years old worldwide by 2050, we must determine the pathophysiologic basis of these disorders so as to treat and prevent them. Solving this challenge will require an interdisciplinary approach. Thus, this is a proposal to establish an Interdisciplinary Research Center in Benign Urology focused on “Molecular and neuroinflammatory biology of aging bladder in normal and disease states”. The overarching, long-term goal of the Center is to catalyze the rapid translation of breakthroughs in our understanding of chronic inflammation in the aged bladder from the preclinical to the clinical setting. The Center will accomplish this by bringing together an interdisciplinary team of physicians and scientists with diverse areas of expertise to systematically investigate markers and mechanisms driving chronic inflammation and its effects in mouse models and in human patients. The team includes practicing urogynecologists and basic and translational scientists interested in infections, age-associated immune dysfunction, and neurobiology of the bladder. The scientific research project proposes that the culprit behind many recurrent UTI and LUTS cases is a chronic neuro-inflammatory process of the bladder mucosa that can present as cystitis cystica, characterized as aggregates of lymphocytes that appear raised on cystoscopy. The Project has three Aims to define the cellular, molecular, immunological, and neurobiological changes that accompany infection and chronic inflammation in the aged bladder in mice and humans. The Center will include an Administrative Core responsible for fostering synergistic collaborations, integrating with existing NIH- sponsored O'Brien Centers in Urological diseases and urology training programs, and overseeing an Educational Enrichment Program. This Program will arrange visits to Washington University by outside speakers to present seminars relevant to the goals of the Center. The Program will also initiate didactic and practical Summer Scholar Research Experiences in Urogynecology-relevant labs for high school, college, and medical students. Together, the research and educational activities supported by the Center will allow the Team to increase interest in urology research and make substantial inroads into understanding the pathophysiology of recurrent UTIs and LUTS.

项目摘要 近50%的绝经后妇女患有尿路感染（UTIs），超过25%的绝经后妇女患有尿路感染。 更年期女性会出现严重的下尿路症状（LUTS），包括尿急， 失禁和排尿疼痛。鉴于到2050年，全球将有近15亿人年满65岁， 我们必须确定这些疾病的病理生理基础，以便治疗和预防它们。解决这个 挑战将需要跨学科的方法。因此，这是一个建立跨学科的建议， 良性泌尿外科研究中心专注于“衰老膀胱的分子和神经炎症生物学 在正常和疾病状态下”。该中心的首要长期目标是促进快速翻译 我们对老年膀胱慢性炎症从临床前到临床的理解取得了突破 临床设置。该中心将通过汇集一个跨学科的医生团队来实现这一目标， 具有不同专业领域的科学家，系统地研究推动慢性 炎症及其在小鼠模型和人类患者中的作用。团队包括练习 泌尿妇科医生和基础和翻译科学家感兴趣的感染，年龄相关的免疫 以及膀胱的神经生物学。科学研究项目提出， 许多复发性UTI和LUTS病例是膀胱粘膜的慢性神经炎症过程， 表现为囊性膀胱炎，特征为膀胱镜检查时出现淋巴细胞聚集。的 项目有三个目标，以确定细胞，分子，免疫学和神经生物学的变化， 伴随感染和慢性炎症在小鼠和人类的老化膀胱。该中心将包括 一个负责促进协同合作的行政核心，与现有的NIH整合， 赞助奥布莱恩中心的泌尿疾病和泌尿外科培训计划，并监督教育 强化计划。本计划将安排校外演讲人访问华盛顿大学， 与中心目标相关的研讨会。该计划还将启动教学和实践的夏季学者 在泌尿妇科学相关实验室的研究经验，高中，大学和医学生。我们一起努力， 该中心支持的研究和教育活动将使该团队增加对泌尿外科的兴趣 研究并取得实质性进展，了解复发性UTI和LUTS的病理生理学。