STRUCTURE/FUNCTION STUDY OF A PROSTAGLANDIN TRANSPORTER

布伦达·陈博士在西奈山医学院获得医学博士学位， 是蒙特菲奥里医疗中心的内科住院医生， 他是阿尔伯特·爱因斯坦医学院的肾病学研究员 1993年。在过去的两年里，她投入了超过80%的时间， 在赞助商的实验室，对一种病毒的分子机制进行基础研究 新型前列腺素(PG)转运蛋白(“PGT”) 陈冯富珍近期的职业目标是将至少75%的时间 在未来五年内开展基础研究，以促进 她在膜运输和分子方面的技术和概念技能 生物学。强化培训计划将包括1)正式评估 咨询委员会；2)参与广泛的爱因斯坦科学研究 社区，包括膜运输中的群体；3)密切监督 在赞助商的实验室里；4)保护她75%的研究时间。Dr。 陈冯富珍的长期职业目标是让自己成为一个独立的 肾脏有机阴离子膜转运领域的研究人员 一个学术肾脏科。 赞助商的实验室研究了两个相关的有机阴离子转运体。“PGT”， 一种PG转运蛋白在肾乳头中强烈表达，转运PGE2， PGF2α和血栓素B2，并似乎介导PG代谢 通行证。表示在S3笔刷边框中的“OATP”主要是运输 结合类固醇。陈博士描述了PGT的几种机制 使用非洲爪哇卵母细胞表达系统进行运输。最近，她 已经开始使用定点突变来解决PGT的拓扑结构， 结合部位和带电残基。申请者的主要目标是 明确前列腺素T的结构-功能关系，以理解 特别是PG的转运机制，以及有机阴离子的转运 总体而言。 这项建议的具体目的是：1)识别膜 用表位标记和N-糖基化扫描研究PGT的拓扑结构 诱变；2)鉴定底物结合部位和 半胱氨酸诱变和氨基酸修饰的易位途径 试剂。这一结果可能会产生广泛而重要的影响 为肾脏病，并将使更好的一般了解有机 负离子传输。

Dr. Brenda Chan received her M.D. from the Mount Sinai School of Medicine, was an Internal Medicine resident at Montefiore Medical Center, and has been a Nephrology Fellow at the Albert Einstein College of Medicine since 1993. For the past two years she has devoted greater than 80% of her time, in the sponsor's lab, to basic research on the molecular mechanisms of a novel prostaglandin (PG) transporter ("PGT"). Dr. Chan's immediate career goals are to devote at least 75% of her time over the next five years to bench research so as to foster development of her technical and conceptual skills in membrane transport and molecular biology. An intense training program will include 1) formal evaluation by an Advisory Committee; 2) involvement in the broad Einstein scientific community, including the group in membrane transport; 3) close supervision in the Sponsor's lab; 4) protection of 75% of her time for research. Dr. Chan's long-term career goals are to establish herself as an independent investigator in the area of renal organic anion membrane transport within an academic nephrology division. The Sponsor's lab studies two related organic anion transporters. "PGT", a PG transporter expressed strongly in the renal papilla, transports PGE2, PGF2alpha, and thromboxane B2, and appears to mediate PG metabolic clearance. "OATP", expressed in the S3 brush border, transports primarily conjugated steroids. Dr. Chan has characterized several mechanisms of PGT transport using the Xenopus oocyte expression system. More recently she has used site-directed mutagenesis to begin to address PGT's topology, binding site, and charged residues. The applicant's broad aims are to define the structure-function relationships of PGT so as to understand mechanisms of PG transport in particular, and of organic anion transport in general. The Specific aims of this proposal are: 1) To identify the membrane topology of PGT by epitope tagging and N-glycosylation scanning mutagenesis; 2) To characterize the substrate binding site and translocation pathway using cysteine mutagenesis and amino acid modifying reagents. The results will likely have broad and important implications for nephrology, and will allow a better general understanding of organic anion transport.