Understanding the Cellular Pathways of Nuclear Receptor Activation

药物治疗的成功关键取决于特异性，即在靶部位刺激治疗反应，并避免在其他（潜在毒性）部位活动。该项目旨在探索药物与细胞质中结合蛋白的相互作用如何诱导核转运和核受体的组织特异性激活-核受体是主要的药物靶点。该项目打算采用分子、结构和细胞生物学方法来绘制药物结合蛋白与受体的相互作用，并确定这些复合物的结构如何决定受体的激活。这些数据可以为设计药物提供路线图，使其与正确组织中的正确蛋白质相互作用，从而显著提高药物的特异性。

The success of drug treatment depends critically on specificity, i.e., stimulation of a therapeutic response at a target site, and avoidance of activity at other (potentially toxic) locations. This project aims to explore how drug interactions with binding proteins in the cytosol can induce nuclear transport and tissue specific activation of nuclear receptors - a major drug target. The project intends to employ molecular, structural and cell biology approaches to map drug-binding protein-receptor interactions and to determine how the structure of these complexes dictates receptor activation. The data could provide a roadmap to design drugs that interact with the right protein in the right tissue and in doing so dramatically enhance drug specificity.