The overall objective of this """"""""Research Center of Excellence in Pediatric Nephrology and Urology"""""""" is to provide a coordinated, interdisciplinary, and multi-institutional approach to study the development of the kidney during embryonic, fetal and postnatal life. The main theme of this Research Center is """"""""Structural and Functional Development of the Kidney: 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, sodium homeostasis, and blood pressure regulation, health and disease. The experimental approaches range from examination of embryological, molecular, and cellular biological mechanisms to integrative physiological studies of renal function during development. Project 1 will investigate the regulation of renin cell identity. Project 2 will study the role of G protein - coupled receptor - kinase gene variants in the pathogenesis of hypertension. Project 3 will investigate the development of tubular polarity during normal and pathological states. Project 4 will define the intercellular signaling in obstructive uropathy. Two pilot projects will add new talent and strength to the Center. Pilot 1 deals with dopamine receptor associated proteins and hypertension. Pilot 2 addresses the role of beta-adrenergic receptor variants in genetic hypertension. The Research Center will be supported by two core facilities: administrative and education. The accomplishments during the previous funding period provide assurance that this Research Center has the necessary manpower, focus, commitment, and institutional support to accomplish the proposed goals. It is anticipated that the Center of Excellence will build on the achievements of the past five years and 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 #
2P50DK052612-06
Application #
6468247
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (J1))
Program Officer
Moxey-Mims, Marva M
Project Start
1997-09-01
Project End
2007-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
6
Fiscal Year
2002
Total Cost
$1,109,777
Indirect Cost
Name
University of Virginia
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Gomez, R Ariel; Belyea, Brian; Medrano, Silvia et al. (2014) Fate and plasticity of renin precursors in development and disease. Pediatr Nephrol 29:721-6
Jose, Pedro A; Soares-da-Silva, Patricio; Eisner, Gilbert M et al. (2010) Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation. Biochim Biophys Acta 1802:1259-67
Lysiak, Jeffrey J; Kirby, Jennifer L; Tremblay, Jacques J et al. (2009) Hypoxia-inducible factor-1alpha is constitutively expressed in murine Leydig cells and regulates 3beta-hydroxysteroid dehydrogenase type 1 promoter activity. J Androl 30:146-56
Reinking, Benjamin E; Wedemeyer, Elesa W; Weiss, Robert M et al. (2009) Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways. Cardiovasc Diabetol 8:43
Hinze, Claas H; Suzuki, Michiko; Klein-Gitelman, Marisa et al. (2009) Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity. Arthritis Rheum 60:2772-81
Zeng, Chunyu; Asico, Laureano D; Yu, Changqing et al. (2008) Renal D3 dopamine receptor stimulation induces natriuresis by endothelin B receptor interactions. Kidney Int 74:750-9
Li, Hewang; Li, Hui-Fang; Felder, Robin A et al. (2008) Rab4 and Rab11 coordinately regulate the recycling of angiotensin II type I receptor as demonstrated by fluorescence resonance energy transfer microscopy. J Biomed Opt 13:031206
Zeng, Chunyu; Armando, Ines; Luo, Yingjin et al. (2008) Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice. Am J Physiol Heart Circ Physiol 294:H551-69
Pentz, Ellen Steward; Lopez, Maria Luisa S Sequeira; Cordaillat, Magali et al. (2008) Identity of the renin cell is mediated by cAMP and chromatin remodeling: an in vitro model for studying cell recruitment and plasticity. Am J Physiol Heart Circ Physiol 294:H699-707
Gildea, John J; Wang, Xiaoli; Jose, Pedro A et al. (2008) Differential D1 and D5 receptor regulation and degradation of the angiotensin type 1 receptor. Hypertension 51:360-6

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