Investigating the Genetic, Cellular, and Metabolic Events Important for Urothelial Homeostasis and Response to Urinary Tract Infection

研究对尿路上皮稳态和尿路感染反应重要的遗传、细胞和代谢事件

• 批准号: 9921173
• 负责人: JONATHAN M. BARASCH
• 金额: $ 120万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-24 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9921173
• 关键词: Address; Atmosphere; Benign; Biomedical Research; Bladder; Cell Differentiation process; Child; Childhood; Cities; Clinical; Collaborations; Communities; Consultations; Country; Data Set; Defect; Development; Disease; Education; Escherichia coli Infections; Event; Evolution; Fostering; Funding; Future; Genes; Genetic; Genitourinary system; Genome; Genomics; Health; Heme; Homeostasis; Host Defense Mechanism; Human; Immune; Infrastructure; Institution; Interdisciplinary Study; Intervention; Iron; Journals; Kidney; Knowledge; Lead; Medical; Medical center; Medicine; Metabolic; Metabolic Pathway; Methods; Microbial Genetics; Minority; Minority Outreach Program; Morbidity - disease rate; Mutagenesis; National Institute of Diabetes and Digestive and Kidney Diseases; Natural regeneration; Nature; New England; New York City; Organ; Pathogenesis; Pathway interactions; Pilot Projects; Population; Prevention; Publications; Reflux; Research; Research Design; Research Personnel; Research Project Grants; Resources; Role; SECTM1 gene; Science; Scientist; Series; Services; Shapes; Squamous Differentiation; Structural defect; Students; Training; Training Programs; Transcriptional Regulation; United States; Universities; Ureter; Urethra; Urinary Microbiome; Urinary tract; Urinary tract infection; Urogenital Diseases; Urology; Urothelial Cell; Urothelium; Woman; Work; base; biobank; career; cell type; clinical investigation; cohort; comparative genomics; data resource; data sharing; educational atmosphere; exome sequencing; experience; human model; innovation; interdisciplinary approach; interdisciplinary collaboration; men; microbial; microbiome analysis; mouse model; multidisciplinary; next generation; novel; outreach; prevent; programs; receptor; recruit; repaired; response; response to injury; risk variant; success; summer research; summer student; symposium; transcriptome sequencing; urinary; urinary tract obstruction; urologic

OVERALL: PROJECT SUMMARY/ABSTRACT The Columbia University George M. O’Brien Urology Cooperative Research Center brings together an experienced group of investigators with a long track record of productive collaboration to address the causes of the most common benign genitourinary disease, urinary tract infection (UTI). UTIs are prevalent in the United States with 13.3% of women, 2.3% of men and 3.4% of children requiring medical intervention due to E. coli infection of the urethra, bladder, ureter, and kidney. Since 2014, the Columbia O’Brien Research Center has investigated the origins of common developmental defects of the pediatric genitourinary system that cause urinary tract obstruction in human and mouse models. For the proposed renewal application, the Center will build upon these efforts and employ a multidisciplinary approach to address the genetic, cellular, and metabolic events that are important in maintaining urothelial homeostasis and that contribute to the body’s response to UTI. The Center consists of three Research Projects, a new Microbial Genomics Biomedical Core (MGBC), and an Administrative Core. Project 1 will determine the influence of the host genome and the urinary microbiome in UTI, as well as genitourinary structural defects in humans. Project 2 will use mouse models to investigate how the transcriptional regulation of urothelial differentiation differs between normal homeostasis and repair during UTI. Project 3 will elucidate how a novel metabolic pathway, the “heme machine”, regulates UTI in the bladder. The scientific aims for each of these projects are highly interconnected, and will require a dynamic exchange of knowledge, seamless data sharing, and multidisciplinary, collaborative efforts to achieve success. To achieve these aims, the three projects will be supported by the MGBC that will provide high-quality services for biobanking, extended bacterial culture, microbial genomics (microbiome analyses, comparative genomics, RNASeq), microbial genetics, and consultation for study design. Additionally, the Administrative Core will provide the supporting framework for the Projects and MGBC in addition to integrating and overseeing all of the Center’s activities including the Educational Enrichment Program and the Opportunity Pool Program. Over the past five years, the Center has placed a major emphasis on educating the next generation of clinician-scientists in urologic research, with annual retreats, seminar series, a summer student training program, and minority outreach programs. We have also successfully used the Opportunity Pool mechanism to interact with other NIDDK-funded centers and to attract new investigators to study important disorders in benign urology. Building on our experience from the last five years and leveraging the infrastructure of Columbia’s top-tier biomedical research institution, this proposed renewal will continue to foster multi- and interdisciplinary collaborations between basic, translational, and clinical researchers. The Center will also address questions related to the genetic, cellular, and metabolic events that lead to UTI, while providing opportunities for educational enrichment and engaging investigators from within urology and other fields to serve the larger urological research community.

总体：项目总结/摘要 哥伦比亚大学乔治M.奥布莱恩泌尿外科合作研究中心汇集了一个 一组经验丰富的调查人员，长期以来一直在进行富有成效的合作， 最常见的良性泌尿生殖系统疾病，尿路感染（UTI）。UTI在美国很普遍， 13.3%的妇女、2.3%的男子和3.4%的儿童因E.杆菌 尿道、膀胱、输尿管和肾脏的感染。自2014年以来，哥伦比亚奥布莱恩研究中心 调查了导致儿童泌尿生殖系统常见发育缺陷的起源， 人和小鼠模型中的尿路梗阻。对于建议的更新申请，中心将建立 在这些努力的基础上，采用多学科方法来解决遗传、细胞和代谢事件， 这是重要的维持尿路上皮稳态，并有助于身体的反应UTI。的 中心由三个研究项目组成，一个新的微生物基因组学生物医学核心（MGBC），和一个 行政核心。项目1将确定宿主基因组和尿液微生物组对感染的影响。 UTI，以及人类的泌尿生殖系统结构缺陷。项目2将使用小鼠模型来研究 在正常稳态和修复过程中，尿路上皮分化的转录调节不同， 尿路感染。项目3将阐明一种新的代谢途径，“血红素机”，如何调节膀胱尿路感染。 这些项目中每一个的科学目标都是高度相互关联的，需要动态地交流， 知识、无缝数据共享和多学科协作努力以取得成功。实现 为了实现这些目标，这三个项目将得到MGBC的支持，MGBC将为以下方面提供高质量的服务： 生物库，扩展细菌培养，微生物基因组学（微生物组分析，比较基因组学， RNASeq）、微生物遗传学和研究设计咨询。此外，行政核心将提供 项目和MGBC的支持框架，以及整合和监督中心的所有 活动包括教育充实计划和机会池计划。过去五 多年来，该中心一直把重点放在教育下一代的临床科学家在泌尿外科 研究，与年度务虚会，研讨会系列，暑期学生培训计划，和少数民族外展 程序.我们还成功地利用机会池机制与其他NIDDK资助的 中心，并吸引新的研究人员研究良性泌尿外科的重要疾病。充分发挥两国 过去五年的经验和利用哥伦比亚顶级生物医学研究的基础设施 机构，这一拟议的更新将继续促进基础， 翻译和临床研究人员。该中心还将解决与遗传、细胞和 导致UTI的代谢事件，同时提供教育丰富和参与的机会， 来自泌尿外科和其他领域的研究人员，为更大的泌尿外科研究社区服务。