Transcriptional regulation of urothelial differentiation and cell type specification during homeostasis and regeneration

项目2：项目摘要/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的使命是 促进对良性泌尿生殖系统疾病/疾病的认识。该中心由一个 管理(管理)核心，微生物基因组生物医学研究核心，以及三个研究项目 这包括临床前和临床研究。我们的重点包括：(1)宿主基因组和宿主基因组的交集 尿微生物组；(2)尿上皮细胞分化在动态平衡和修复过程中的转录调控 对尿路感染的反应；(3)尿液化学和尿路上皮铁代谢(“铁-血红素”)的调节 机器“)是尿路上皮对尿路感染反应的一个组成部分。我们预期拟议的研究将会 为与良性泌尿外科高度相关的疾病的发病机制提供新的见解，并促进 将基因检测引入泌尿外科实践，甚至提出新的治疗方法。我们将研究 宿主和入侵细菌之间的相互作用以及营养铁在UT结局中的作用 感染；我们将进行一项新的GWAS分析，以寻找导致LUTD的突变，包括 失禁、梗阻和盆底脱垂，我们将分析患者的尿菌群 下尿路功能障碍(LUTD)，我们建议确定编程尿路上皮细胞类型的途径 这可能用于治疗与疾病相关的良性尿路上皮异常。最重要的目标是 该中心旨在利用泌尿外科社区的专业知识和经验来扩大我们的 研究并帮助指导我们将解决的各种问题。我们已经直接整合了 P20/U54社区以及良性泌尿科社区的临床医生和科学家。共同调查员 我们的项目包括Indira Mysorekar(20岁)，泌尿系感染和尿路上皮生物学专家，她将与Dr。 Mendelsohn和Barasch博士，Chad Vezina(威斯康星州U54)以及来自 良性泌尿科社区，(Lori Birder，Gerry Apodaca，Doug Strand)。此外，我们还邀请了 外部专家加入我们的工作，例如，血红素生物学家伊克巴尔·哈姆扎(马里兰大学)。我们 也高度关注教育和外展：我们的暑期项目已经培训了73名学生，从我们的 中心现已建成，包括本科生、四年级医学生和泌尿外科住院医师。我们 已经向普通蒂博士(洛约拉大学)和凯瑟琳·布朗斯坦博士(哈佛大学)提供了机会池资金 大学)。我们在2019年10月举办了一次非常成功的研讨会：UTI的问题： 《泌尿生殖道微生物群及其免疫防御》汇聚十几位专家与&gt；138 泌尿外科社区的成员。

PROJECT 2: PROJECT SUMMARY/ABSTRACT The mission of the Columbia University George M. O’Brien Urology Cooperative Research Center is to advance the understanding of benign genitourinary diseases/disorders. The Center consists of an Administrative (Admin) Core, a Microbial Genomics Biomedical Research Core, and three Research Projects that include preclinical and clinical studies. Our focus includes: (1) the intersection of the host genome and the urinary microbiome; (2) the transcriptional regulation of urothelial differentiation during homeostasis and repair in response to UTI; and (3) how the regulation of urinary chemistry and urothelial iron metabolism (“iron-heme machine”) is a component of the urothelial response to UTI. We anticipate that the proposed studies will provide new insight into the pathogenesis of disorders of high relevance to benign urology and also facilitate introduction of genetic testing into the practice of Urology and even suggest new treatments. We will examine the interactions between host and invading bacteria, and the role of nutrient iron in shaping the outcome of UT infections; we will undertake a new GWAS analysis to search for mutations that lead to LUTD, including incontinence, obstruction and pelvic floor prolapse, we will analyze the urinary microbiome of patients with lower urinary tract disfunction (LUTD), and we propose to identify pathways that program urothelial cell types that may be used to treat benign urothelial abnormalities associated with disease. The most important goal of this center is to utilize the expertise and experience of the urological community to increase the scope of our studies and to help direct the kinds of questions we will address. We have directly integrated members of the P20/U54 community as well as clinicians and scientists in the benign urological community. Co-investigators on our projects include Indira Mysorekar (P20), an expert in UTI and urothelial biology who will work with Dr. Mendelsohn and Dr. Barasch, Chad Vezina (Wisconsin U54) and collaborating scientists and clinicians from the benign urological community, (Lori Birder, Gerry Apodaca, Doug Strand). In addition, we have invited outside experts to join our work, for example, the heme biologist, Iqbal Hamza (University of Maryland). We are also highly focused on education and outreach: Our summer program has trained 73 students since our center has been established, including undergraduates, fourth year medical students and urology residents. we have provided opportunity pool funds to Dr. Putonti (Loyola University) and Dr. Catherine Brownstein, (Harvard University). We held a Symposium in October of 2019 that was extremely successful "The problem of UTI: The microbiome of the Urogenital Tract and its immune Defense" bringing together a dozen experts with >138 members of the Urological community.