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.

Public Health 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Specialized Center (P50)
Project #
5P50DK096373-03
Application #
8730636
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Moxey-Mims, Marva M
Project Start
2012-09-21
Project End
2017-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Virginia
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Gomez, R Ariel; Lopez, Maria Luisa S Sequeira (2017) Plasticity of Renin Cells in the Kidney Vasculature. Curr Hypertens Rep 19:14
Oka, Masafumi; Medrano, Silvia; Sequeira-L?pez, Maria Luisa S et al. (2017) Chronic Stimulation of Renin Cells Leads to Vascular Pathology. Hypertension 70:119-128
Chevalier, Robert L (2017) Evolutionary Nephrology. Kidney Int Rep 2:302-317
Song, Renfang; Lopez, Maria Luisa S Sequeira; Yosypiv, Ihor V (2017) Foxd1 is an upstream regulator of the renin-angiotensin system during metanephric kidney development. Pediatr Res 82:855-862
Gomez, R Ariel (2017) Fate of Renin Cells During Development and Disease. Hypertension 69:387-395
Hilliard, Sylvia A; El-Dahr, Samir S (2016) Epigenetics of Renal Development and Disease. Yale J Biol Med 89:565-573
Shinohara, Keisuke; Liu, Xuebo; Morgan, Donald A et al. (2016) Selective Deletion of the Brain-Specific Isoform of Renin Causes Neurogenic Hypertension. Hypertension 68:1385-1392
Sequeira-Lopez, Maria Luisa S; Torban, Elena (2016) New insights into precursors of renal endothelium. Kidney Int 90:244-246
Hu, Yan; Li, Minghong; Göthert, Joachim R et al. (2016) Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development. J Am Soc Nephrol 27:1984-95
Lu, Ko-Ting; Keen, Henry L; Weatherford, Eric T et al. (2016) Estrogen Receptor ? Is Required for Maintaining Baseline Renin Expression. Hypertension 67:992-9

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