The Analytical Core (Core B) will be organized to provide high quality, reproducible, low cost, automated high-throughput robotic analytical services to the four projects as well as the Animal Core (Core C). The core will be managed and staffed with experts who have demonstrated an ability to develop, engineer, and implement the assays necessary to support the proposed activities of the Analytical Core. The Analytical core will be organized around 4 major services/specific aims.
Specific Aim 1 : To provide high quality, reproducible automated assays to support Projects 1-3 and the Animal Core.
Specific Aim 2 : To provide genotyping services for projects #1 and #2. We will test for the presence of SNPs in GRK4, angiotensin converting enzyme (ACE l/D), aldosterone synthase, angiotensinogen, and ATIR using our previously published method {Bengra, 2002, 12446468} with a data reducfion method (Moore, Pub Med ID 12108579). Additional SNPs will be added as needs arise.
Specific Aim 3 : To provide cultured human renal proximal tubule cells for projects #1and #3 using a novel patent pending 3D cell culture method. We will also use our method to isolate individual renal proximal tubular cells (RPTCs) from fresh specimens of human urine in order to provide greater genetic diversity for studying human physiology, to correlate in vitro cellular responses to in vivo responses in the same patients as studied in Project 2.
Specific Aim 4 : To provide cellular imaging services to support projects #1 and #3. In addition, in support of project #2, we will perform human kidney slice culture and subsequent confocal analysis of DIR and DSR localization.

Public Health Relevance

Core B will develop and use novel analytical techniques to support the needs of the PPG, and to conduct its own hypothesis driven research. Undoubtedly, Core B will also publish its novel analytical developments in the form of patents and original publications.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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University of Virginia
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Diao, Zhenyu; Asico, Laureano D; Villar, Van Anthony M et al. (2017) Increased renal oxidative stress in salt-sensitive human GRK4?486V transgenic mice. Free Radic Biol Med 106:80-90
Yatabe, Midori Sasaki; Iwahori, Toshiyuki; Watanabe, Ami et al. (2017) Urinary Sodium-to-Potassium Ratio Tracks the Changes in Salt Intake during an Experimental Feeding Study Using Standardized Low-Salt and High-Salt Meals among Healthy Japanese Volunteers. Nutrients 9:
Konkalmatt, Prasad R; Asico, Laureano D; Zhang, Yanrong et al. (2016) Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure. JCI Insight 1:
Jose, Pedro A (2016) Gastrorenal communication: sniffing and tasting. Exp Physiol 101:457-8
Wang, Zheng; Zeng, Chunyu; Villar, Van Anthony M et al. (2016) Human GRK4?142V Variant Promotes Angiotensin II Type I Receptor-Mediated Hypertension via Renal Histone Deacetylase Type 1 Inhibition. Hypertension 67:325-34
Carey, Robert M (2016) Resistant Hypertension: Mineralocorticoid Receptor Antagonist or Renal Denervation? Hypertension 67:278-80
Jose, Pedro A; Yang, Zhiwei; Zeng, Chunyu et al. (2016) The importance of the gastrorenal axis in the control of body sodium homeostasis. Exp Physiol 101:465-70
Jose, Pedro A; Felder, Robin A; Yang, Zhiwei et al. (2016) Gastrorenal Axis. Hypertension 67:1056-63
Sanada, H; Yoneda, M; Yatabe, J et al. (2016) Common variants of the G protein-coupled receptor type 4 are associated with human essential hypertension and predict the blood pressure response to angiotensin receptor blockade. Pharmacogenomics J 16:3-9
Yu, Changqing; Chen, Jianghua; Guan, Weiwei et al. (2015) Activation of the D4 dopamine receptor attenuates proliferation and migration of vascular smooth muscle cells through downregulation of AT1a receptor expression. Hypertens Res 38:588-96

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