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

描述（由申请人提供）：该“儿科肾脏学卓越中心”的总体目标是提供一种协调的、跨学科的和跨机构的方法来研究胚胎、胎儿和出生后肾脏的发育。该研究中心的主题是“肾脏发育和疾病：年轻人和成年人的细胞命运和疾病前兆”。“从广义上讲，拟议的研究涉及儿科肾病临床相关的基本问题，例如对健康和疾病中肾脏形态发生和稳态的理解。实验方法包括检查控制细胞命运、可塑性和身份的表观遗传机制，以及肾损伤和修复过程中发生的表型转化的细胞信号。项目1将研究RBP-J在肾血管系统谱系关系中的作用（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将研究经典Wnt对肾组织命运和功能的调节（Jing Yu，UVA）。项目4将阐明无小管肾小球形成的细胞机制，这是一种广泛的肾脏疾病中肾单位丢失的普遍和未被认识的途径（Robert Chevalier，UVA）。该计划的总主题内的试点和可行性项目（PFP）将从大学和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的示例包括：Pilot 1解决了p53介导的Wnt/β连环蛋白信号传导调节在新生肾单位形成中的作用（Zubaida Saifuidine，Tulane），Pilot 2解决了Jagged 1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发资源，实施征求和选择PFP候选人的程序，维护一个中心网站和一个充实/教育计划，为支持研究生提供资源，开发存储库数据，举办讲习班，研讨会和专题讨论会，以加强肾脏发育和疾病的研究。这个肾脏病卓越儿科中心拥有必要的专业知识，人力，重点，承诺和机构支持，以实现拟议的目标。预计该卓越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：通过儿科肾脏病学卓越中心促进的研究和科学交流所获得的知识进步将增加科学认识，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.