The long-term goal of the project is to establish the physiological roles of two related transport proteins, MATE1 and MATE2-K, in the renal secretion of drugs from the human body. This goal will be approached by determining (1) the unique substrate selectivities of these two transporters, (2) where each is expressed along the length of the human renal proximal tubule, and (3) their relative influence on drug transport in primary cultures of human renal proximal tubule cells. These experiments will entail use of methods of cell culture, heterologous protein expression, kinetic analysis of membrane transport, QSAR modeling of transport protein selectivity, immunuhistochemistry, and RNAi knockdown of native protein expression in primary human renal cells. Acquiring these techniques, and the trainining associated with their use in the study of renal transport physiology, will help propel me forward to a career of biomedical research in the area of renal physiology and pharmacology of drug handling. The results of this study will assist in the development of a preditive model of substrate/inhibitor interaction with drug transporters in the human kidney. This information may help eliminate or reduce unwanted drug- drug interactions.
