Regulation of minerals and fluids excretion in vitamin D

描述（改编自应用程序） Yan Chun Li，Ph.D.，获得了博士学位肯特州立大学生物化学学位 大学在麻省理工学院和哈佛医学院接受博士后培训后， 加入芝加哥大学担任医学助理教授。 李博士的长期职业目标是发展成为一个领先的独立 维生素D研究领域的研究者，长期目标是 了解维生素D内分泌系统的生理功能。作为 李医生没有接受过正规的生理学训练，建议五年职业生涯 发展计划将使他接受广泛的培训， 维生素D内分泌系统的生理学和维生素D 维生素D缺乏，特别是在矿物质的维生素D调节方面 新陈代谢.本申请的申办者Brasitus博士是 维生素D信号在正常和肿瘤细胞的国际权威。的 研究咨询委员会，由博士组成。Brasitus，Sitrin，Favus和Graves， 一群国际知名的医学科学家， 在维生素D研究领域的研究经验和专业知识， 为李博士正在进行的研究提供合作和建议。 李博士的研究计划是研究肾脏排泄的调节， 钙，钠和体液的1，25-二羟维生素D3 [1，25（OH）2D 3]，使用 维生素D受体（VDR）缺失小鼠模型。研究将集中在肾脏 钙结合蛋白-D9 k（CaBP-D9 k），参与跨细胞 钙转运和心钠素（ANP），一种心脏源性 促进钠和水排泄的激素。第一个目标是研究 VDR失活、1，25（OH）2-维生素D缺乏和膳食钙的影响 对肾脏CaBP-D9 k表达的影响及其在钙重吸收中的作用。的 第二个目的是研究肾脏CaBP-D9 k表达的调节， 1，25（OH）2D 3以及1，25（OH）2D 3诱导的CaBP-D9 k的调节 通过PTH或钙表达，使用VDR（+/+）和（-/-）初级肾小管 细胞培养这种体外培养系统也将用于分析 CaBP-D9 k基因启动子并鉴定维生素D应答元件。第三 目的是研究VDR失活对ANP表达和钠离子浓度的影响。 和体液平衡，为了在体内测试，假设 1，25（OH）2D 3负性调节ANP表达。

DESCRIPTION (adapted from the 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 is 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 is 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.