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 #
1P50DK096373-01
Application #
8368309
Study Section
Special Emphasis Panel (ZDK1-GRB-G (M3))
Program Officer
Moxey-Mims, Marva M
Project Start
2012-09-21
Project End
2017-08-31
Budget Start
2012-09-21
Budget End
2013-08-31
Support Year
1
Fiscal Year
2012
Total Cost
$909,599
Indirect Cost
$248,875
Name
University of Virginia
Department
Pediatrics
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
El-Dahr, Samir; Hilliard, Sylvia; Aboudehen, Karam et al. (2014) The MDM2-p53 pathway: multiple roles in kidney development. Pediatr Nephrol 29:621-7
Galarreta, Carolina I; Grantham, Jared J; Forbes, Michael S et al. (2014) Tubular obstruction leads to progressive proximal tubular injury and atubular glomeruli in polycystic kidney disease. Am J Pathol 184:1957-66
McLaughlin, Nathan; Wang, Fenglin; Saifudeen, Zubaida et al. (2014) In situ histone landscape of nephrogenesis. Epigenetics 9:222-35
Chevalier, Robert L; Forbes, Michael S; Galarreta, Carolina I et al. (2014) Responses of proximal tubular cells to injury in congenital renal disease: fight or flight. Pediatr Nephrol 29:537-41