Multidrug and Toxin Extrusion's (MATE) role in renal organic cation secretion

项目描述（由申请人提供）：该项目的长期目标是建立两种相关转运蛋白MATE1和MATE2-K在人体药物的肾脏分泌中的生理作用。这一目标将通过确定(1)这两种转运蛋白独特的底物选择性，(2)每一种转运蛋白沿着人肾近端小管的长度表达，以及(3)它们在人肾近端小管细胞原代培养中对药物转运的相对影响来实现。这些实验将需要使用细胞培养、异种蛋白表达、膜转运动力学分析、转运蛋白选择性的QSAR建模、免疫组织化学和RNAi敲除人原代肾细胞中天然蛋白表达的方法。掌握这些技术，以及在肾脏转运生理学研究中使用这些技术的相关培训，将有助于推动我在肾脏生理学和药物处理药理学领域从事生物医学研究。这项研究的结果将有助于开发底物/抑制剂与人类肾脏中药物转运体相互作用的预测模型。这些信息可能有助于消除或减少不必要的药物相互作用。

DESCRIPTION (provided by applicant): 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.