Regulation of Cell Fate during Kidney Development and Disease

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SUMMARY The overall goal of this “Pediatric Center of Excellence in Nephrology” is to provide a coordinated, interdisciplinary approach to study the development of the kidney vasculature during embryonic, fetal and postnatal life. The main theme of this Research Center is “Regulation of Cell Fate during Kidney Development and Disease.” Broadly, the proposed research deals with fundamental questions of clinical relevance in Pediatric Nephrology such as the understanding of the proper development, and the structural and functional maintenance of the kidney vasculature 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 when homeostasis is threatened in early life. Project 1 will investigate the role of renin cell progenitors in the development and pathology of the kidney arterioles (R. Ariel Gomez and Maria Luisa Sequeira Lopez). Project 2 will define how the TGFb/FGF2 axis controls the fate of renin and vascular smooth muscle cells under conditions that threaten homeostasis in infancy (Patricio Ray, Agnes Swiatecka-Urban and Jennifer Charlton). Pilot and Feasibility projects within the general theme of the Center will be solicited at a national level from universities at large, the ASPN, the ASN and adult nephrology programs with the objective to add new talent to the investigation of renal diseases in children. This will be done in coordination with the other 2 PCENs to avoid overlap and guarantee the best outcome for each project. A cutting- edge Core in Single Cell Epigenomics, Transcriptomics and Bioinformatics (Nathan Sheffield, Silvia Medrano) will add scientific and technical expertise to individual laboratories within and outside the Center. The Center will be supported by an Administrative Core which will allocate and distribute resources to Center participants, implement the Opportunity Pool Program with procedures for soliciting and selecting candidates for Pilot and Feasibility Awards, maintain a Center Website and an Enrichment / Educational program to provide resources for 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, diverse 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 diseases and hypertension.