Kidney development Cell fate and precursors of disease in the young and adult

描述(由申请人提供)：这个“儿科肾脏学卓越中心”的总体目标是提供一个协调的、跨学科的、跨机构的方法来研究肾脏在胚胎、胎儿和出生后的发育。该研究中心的主题是“肾脏发育和疾病：青少年和成人的细胞命运和疾病的前兆”。广泛地说，拟议的研究涉及儿童肾脏病临床相关的基本问题，例如了解肾脏的形态发生和在健康和疾病中的动态平衡。实验方法包括检查控制细胞命运、可塑性和特性的表观遗传机制，以及在肾脏损伤和修复过程中发生的表型转化的细胞信号。项目1将调查RBP-J在肾脏血管系统血统关系中的作用(Ariel Gomez，UVA)。项目2将研究肾单位祖细胞更新和命运的表观遗传机制(Samir El-Dahr，Tulane)。项目3将研究规范的Wnt对肾间质命运和功能的调节(于静，UVA)。项目4将阐明肾小管小球形成的细胞机制，这是一种普遍存在的、在广泛的肾脏疾病中肾单位丢失的未被认识的途径(Robert Chvalier，UVA)。该计划总主题内的试点和可行性项目(PFP)将向普通大学和ASPN征求意见，目的是为儿童肾脏疾病的研究增加新的人才。PFP的例子包括：Pilot 1解决了P53介导的Wnt/pcatenin信号在新生肾单位形成中的作用(Zubaida Saifudeen，Tulane)，Pilot 2解决了Jagged1在肾血管发育中的作用(Brian Belyea，UVA)。该中心将得到一个行政核心的支持，该行政核心将向中心参与者分配和分配资源，执行招募和挑选私营部门合作伙伴候选人的程序，维护一个中心网站和一个充实/教育方案，为支持研究学生、开发资料库数据、讲习班、研讨会和专题讨论会提供资源，以加强肾脏发展和疾病方面的研究。这个儿科肾病学卓越中心拥有必要的专业知识、人力、专注、承诺和机构支持，以实现拟议的目标。预计英才中心将改善对患有肾脏和泌尿系统疾病的婴儿和儿童的管理。 相关性：通过该儿科肾脏病卓越中心促进的研究和科学交流，在知识方面取得的进展将增加科学认识，从而改善对患有肾脏和泌尿系统疾病的婴儿和儿童的管理。

DESCRIPTION (provided by applicant): The overall objective of this "Center of Excellence in Pediatric Nephrology" is to provide a coordinated, interdisciplinary, and inter-institutional approach to study the development of the kidney during embryonic, fetal and postnatal life. The main theme of this Research Center is "Kidney Development and Disease: Cell Fate and Precursors of Disease in the Young and Adult." Broadly, the proposed research deals with fundamental questions of clinical relevance in Pediatric Nephrology such as the understanding of kidney morphogenesis and homeostasis in health and disease. The experimental approaches range from examination of epigenetic mechanisms that control cell fate, plasticity, and identity and the cellular signals underlying the phenotypic transformation that occurs during kidney injury and repair. Project 1 will investigate the role of RBP-J in lineage relationships in the kidney vasculature (Ariel Gomez, UVA). Project 2 will examine the epigenetic mechanisms of nephron progenitor cell renewal and fate (Samir El-Dahr, Tulane). Project 3 will investigate canonical Wnt regulation of renal interstitium fate and function (Jing Yu, UVA). Project 4 will elucidate the cellular mechanisms underlying the formation of atubular glomeruli, a pervasive and under-recognized pathway for nephron loss in a broad spectrum of renal disorders (Robert Chevalier, UVA). Pilot and feasibility projects (PFP) within the general theme of the program will be solicited from the Universities at large and the ASPN with the objective to add new talent to the investigation of renal diseases in children. Examples of PFPs include: Pilot 1 addresses the role of p53-mediated regulation of Wnt/pcatenin signaling in nascent nephron formation (Zubaida Saifudeen, Tulane), Pilot 2 addresses the role of Jagged 1 in kidney vascular development (Brian Belyea, UVA). The Center will be supported by an Administrative Core which will allocate and distribute resources to Center participants, implement the procedures for soliciting and selecting candidates for the PFP, maintain a Center website and an Enrichment/Educational program to provide resources for the support of research students, the development of repository data, workshops, seminars and symposia to enhance research in kidney development and disease. This Pediatric Center of Excellence in Nephrology has the necessary expertise, manpower, focus, commitment, and institutional support to accomplish the proposed goals. It is anticipated that the Center of Excellence will lead to improved management of infants and children with renal and urological diseases. RELEVANCE: The advances in knowledge obtained through the research and scientific exchange fostered by this Center of Excellence in Pediatric Nephrology will add to the scientific understanding that will lead to improved management of infants and children with renal and urological diseases.