application) Yan Chun Li, Ph.D., received a Ph.D. degree in biochemistry from Kent State University. After postdoctoral training at MIT and Harvard Medical School, he joined the University of Chicago as an Assistant Professor of Medicine. Dr. Li's long-term career goal is to develop into a leading independent investigator in the field of vitamin D research, with a long-term objective of understanding the physiological functions of the vitamin D endocrine system. As Dr. Li has no formal physiology training, the proposed five-year career development plan will allow him to receive extensive training on general physiology of the vitamin D endocrine system and the pathophysiology of vitamin D deficiency, particularly, in the area of vitamin D regulation of mineral metabolism. The sponsor of the present application, Dr. Brasitus, is an international authority on vitamin D signaling in normal and tumor cells. The Research Advisory Board, formed by Drs. Brasitus, Sitrin, Favus and Graves, is a group of internationally renowned physician-scientists with extensive research experience and expertise in the field of vitamin D research, and will provide collaboration and advice in Dr. Li's ongoing research. Dr. Li's research plan is to study the regulation of renal excretion of calcium, sodium and body fluid by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], using the vitamin D receptor (VDR) null mouse model. Studies will be focused on renal calbindin-D9k (CaBP-D9k), the rate-limiting protein involved in transcellular calcium transport, and atrial natriuretic peptide (ANP), a heart-derived hormone that promotes sodium and water excretion.
The first aim i s to study the effect of VDR inactivation, 1,25(OH)2-vitamin D deficiency, and dietary calcium on the expression of renal CaBP-D9k and its role in calcium reabsorption.
The second aim i s to study the regulation of renal CaBP-D9k expression by 1,25(OH)2D3, as well as the modulation of 1,25(OH)2D3-induced CaBP-D9k expression by PTH or calcium, using VDR(+/+) and (-/-) primary renal tubule cell cultures. This in vitro culture system will also be used to analyze the CaBP-D9k gene promoter and identify the vitamin D response element. The third goal is to study the effect of VDR inactivation on ANP expression and sodium and body fluid balance, in order to test in vivo, the hypothesis that 1,25(OH)2D3 negatively regulates ANP expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK059327-05
Application #
6926960
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2001-08-01
Project End
2006-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
5
Fiscal Year
2005
Total Cost
$124,605
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Li, Yan Chun (2014) Discovery of vitamin D hormone as a negative regulator of the renin-angiotensin system. Clin Chem 60:561-2
Khare, Sharad; Mustafi, Reba; Cerda, Sonia et al. (2008) Ursodeoxycholic acid suppresses Cox-2 expression in colon cancer: roles of Ras, p38, and CCAAT/enhancer-binding protein. Nutr Cancer 60:389-400
Szeto, Frances L; Sun, Jun; Kong, Juan et al. (2007) Involvement of the vitamin D receptor in the regulation of NF-kappaB activity in fibroblasts. J Steroid Biochem Mol Biol 103:563-6
Zhang, Z; Yuan, W; Sun, L et al. (2007) 1,25-Dihydroxyvitamin D3 targeting of NF-kappaB suppresses high glucose-induced MCP-1 expression in mesangial cells. Kidney Int 72:193-201
Sun, Jun; Kong, Juan; Duan, Yingli et al. (2006) Increased NF-kappaB activity in fibroblasts lacking the vitamin D receptor. Am J Physiol Endocrinol Metab 291:E315-22
Kong, Juan; Grando, Sergei A; Li, Yan Chun (2006) Regulation of IL-1 family cytokines IL-1alpha, IL-1 receptor antagonist, and IL-18 by 1,25-dihydroxyvitamin D3 in primary keratinocytes. J Immunol 176:3780-7
Kong, Juan; Li, Yan Chun (2006) Molecular mechanism of 1,25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells. Am J Physiol Endocrinol Metab 290:E916-24
Xiang, Wei; Kong, Juan; Chen, Songcang et al. (2005) Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab 288:E125-32
Bolt, Merry J G; Cao, Li-Ping; Kong, Juan et al. (2005) Vitamin D receptor is required for dietary calcium-induced repression of calbindin-D9k expression in mice. J Nutr Biochem 16:286-90
Qiao, Guilin; Kong, Juan; Uskokovic, Milan et al. (2005) Analogs of 1alpha,25-dihydroxyvitamin D(3) as novel inhibitors of renin biosynthesis. J Steroid Biochem Mol Biol 96:59-66

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