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

稳态和再生过程中尿路上皮分化和细胞类型规范的转录调控

• 批准号: 10297546
• 负责人: CATHY Lee MENDELSOHN
• 金额: $ 23.51万
• 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 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10297546
• 关键词: ATAC-seq; Acute; Address; Adipose tissue; Agonist; Bacteria; Basal Cell; Benign; Biology; Biomedical Research; Blood; Cell Differentiation process; Cells; Chad; Chemistry; Chronic; Clinical Research; Collaborations; Communities; Control Locus; Data; Disease; Down-Regulation; Duct (organ) structure; Education and Outreach; Enterobacteria phage P1 Cre recombinase; Epithelial; Event; Functional disorder; Funding; Genes; Genetic; Genetic Transcription; Genome; Goals; Heme; Heme Iron; Herpesviridae; Homeostasis; Human; Immune; In Situ; Incontinence; Infection; Inflammation; Injury; Intestines; Invaded; Iron; Kidney; Lead; Ligands; Liver; Lower urinary tract; Malignant neoplasm of urinary bladder; Maryland; Medical Students; Metabolic; Mission; Modeling; Mus; Muscle; Mutation; Natural regeneration; Notch Signaling Pathway; Nuclear Receptors; Nutrient; Obstruction; Organoids; Outcome; PPAR gamma; Pathogenesis; Pathway interactions; Patients; Pelvic floor structure; Placenta; Population; Proteins; Ptosis; Regulation; Research; Research Personnel; Research Project Grants; Retinoids; Role; Scientist; Shapes; Signal Pathway; Signal Transduction; Squamous Differentiation; Stretching; Students; Testing; Tissues; Toxin; Training; Transcriptional Regulation; Universities; Up-Regulation; Urinary Microbiome; Urogenital Diseases; Urology; Urothelial Cell; Urothelium; VP 16; Water; Wisconsin; Work; bladder pain; cell type; experience; genetic testing; genome wide association study; insight; insulin sensitizing drugs; iron metabolism; lipid biosynthesis; macrophage; member; microbial genomics; microbiome; mutant; notch protein; preclinical study; prevent; programs; receptor; repaired; response; response to injury; rosiglitazone; stem cells; summer program; symposium; transcriptome sequencing; undergraduate student; urinary; urogenital tract; urologic

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.

项目2：项目总结/摘要 哥伦比亚大学的使命乔治M。奥布莱恩泌尿科合作研究中心是 促进对良性泌尿生殖系统疾病/紊乱的了解。该中心由一个 行政（管理）核心，微生物基因组学生物医学研究核心，和三个研究项目 包括临床前和临床研究。我们的研究重点包括：（1）宿主基因组与 尿微生物组;（2）稳态和修复过程中尿路上皮分化的转录调控 以及（3）尿化学和尿路上皮铁代谢（“铁血红素”）的调节如何影响尿路感染的发生。 机器”）是尿路上皮对UTI反应的组成部分。我们预计，拟议的研究将 为良性泌尿系统高度相关疾病的发病机制提供了新的见解， 将基因检测引入泌尿科实践，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，以及营养铁在形成UT结果中的作用 我们将进行一项新的GWAS分析，以寻找导致LUTD的突变，包括 尿失禁，梗阻和盆底脱垂，我们将分析患者的尿微生物组 下尿路功能障碍（LUTD），我们建议确定的途径，程序尿路上皮细胞类型 其可用于治疗与疾病相关的良性尿路上皮异常。最重要的目标 该中心是利用泌尿外科界的专业知识和经验，以增加我们的范围， 研究，并帮助指导我们将解决的问题。我们已经直接整合了 P20/U 54社区以及良性泌尿外科社区的临床医生和科学家。合作研究 我们的项目包括英迪拉Mysorekar（P20），在UTI和尿路上皮生物学专家谁将与博士。 Mendelsohn和Barasch博士，Chad Vezina（威斯康星州U 54）以及来自 良性泌尿外科群体，（洛里伯德，格里阿波达卡，道格斯特兰德）。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（马里兰州大学）。我们 我们也高度重视教育和推广：我们的暑期课程已经培训了73名学生，因为我们的 中心已成立，包括本科生，四年级医学生和泌尿外科住院医师。我们 我已经向普通蒂博士（洛约拉大学）和凯瑟琳·布朗斯坦博士（哈佛）提供了机会池资金 大学）。我们在2019年10月举办了一个非常成功的研讨会“UTI的问题： 泌尿生殖道微生物组及其免疫防御”汇集了十几位专家， 泌尿外科社区的成员