Characterization of Aquaporin 2 Interacting Proteins

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18. GOALS FOR KIRSCHSTEIN-NRSA FELLOWSHIP TRAINING AND CAREER Lu, Hua, A. J. I NAME OF APPLICANT (Last, INSTITUTION Belling Medical University University of Massachusetts University of Massachusetts first, middle initial) MENTOR Dr. Zhao-Feng Lu, M.D. Dr. John Burand, Ph.D. Dr. John Burand, Ph.D INSTITUTION/COMPANY SUPERVISOR/EMPLOYER Univ. Massachus Dr. J. Burand Univ. Massachus Dr. J. Burand BIDMC, HMS Dr. V. Sukhatme NYUMC Dr. R. Raitch NYUMC Dr. M. Charap MGH, HMS Dr. D. Brown The research proposed in this application will be conducted during my three years of postdoctoral fellowship (July 2002-Jun 2005) at the Massachusetts General Hospital. Immediately after the research years, I am going to complete one year of clinical nephrology fellowship at the same institution. I have extensive training in virology and molecular biology. By joining Dr. Dennis Brown's laboratory, I am very confident that I will be exposed to an excellent scientific environment, where I will learn about the exciting field of renal physiology and pathophysiology. In particular, I will gain additional training in membrane biology/protein trafficking. I believe that this three years' fellowship training will provide me with solid scientific knowledge and extensive experiences to build a strong foundation for a career as an independent investigator. I also see this research fellowship as an integral part of my education, as my goal is to pursue a career in academic nephrology, where I could combine patient care, research and teaching. I _"-zo]_F,1;e]i 19. NAME AND DEGREE(S) Dennis Brown, PhD 20. POSITION/RANK Associate Chief, Renal Unit 21. RESEARCH INTERESTS/AREAS 22. DESCRIPTION Vasopressin (VP) is the major antidiuretic hormone involved in the regulation of water reabsorption by mammalian kidney. Intensive studies have established that VP functions by recruiting the AQP2 water channel from cytoplasmic vesicles to the plasma membrane of collecting duct principal cells. The impairment of VP-AQP2 signaling pathways results in diabetes insipidus as well as fluid retention seen in some heart failure patients. AQP2 is regulated through complex trafficking pathways. Our hypothesis is that regulated trafficking of AQP2 requires direct and indirect protein-protein interactions during intracellular translocation, exocytosis as well as endocytosis. The proposed studies are divided into three specific aims addressing identification and characterization of novel AQP2 interacting proteins as well as investigation of the functional significance of these novel protein interactions on AQP2 trafficking in vitro and in vivo. The proposed study will utilize multidisciplinary approaches (molecular biology, cell biology, biochemistry and immunocytochemistry) and powerful technology (yeast two hybrid screen, structural functional analysis, gene transfer) to identify and characterize novel protein- protein interactions and their biologic functions. These studies will provide important information of the poorly understood molecular mechanisms underlying AQP2 trafficking, and may ultimately lead to better therapies for patients with defective urinary concentration. PHS 416-1 (Rev. 06/02) Form Page 2 Kirschstein-NRSA Individual Fellowship Application NAMEOFAPPLICANT(Last,first, middle initial) Table of Contents ========================================Section End===========================================