申请人一直从事结构药理学这一新兴学科的研究，主要研究对象为G蛋白偶联受体 (GPCR) 。GPCR是已知的最大跨膜受体家族，与多种重大疾病的发生、发展密切相关。在过去的几年时间里，申请人已经成功解析了与心血管疾病相关的嘌呤能受体P2Y12R、P2Y1R以及与艾滋病和自身免疫性疾病相关的趋化因子受体CCR5等多种受体与药物复合物的三维结构。这些研究揭示了许多独特的药物-受体作用方式，为靶向相关受体药物研发中遇到的问题提供了合理的解释，并为后续的药物筛选与优化提供重要的结构基础。申请人计划继续深入结构药理学研究，解析受体-配体、受体-信号分子复合物的三维结构，以进一步了解受体-药物相互作用以及药物的作用机理，辅助药效更高、毒副作用更低的药物开发。

My research is focused on structural pharmacology, which is the intersection of pharmacology with structural biology guides the rational design of therapeutics. Our main research target is G protein-coupled receptor (GPCR), the largest protein superfamily within human genome. It comprises over 800 receptors and ~400 of these receptors are involved in the development of important human diseases. Thus these receptors are the most important drug targets. Previously, we have solved the crystal structures of human purinergic receptor P2Y12R and P2Y1R which are involved in cardiovascular diseases, as well as the crystal structure of chemokine receptor CCR5, which is involved in the infectious of HIV and autoimmune diseases. These structures reveal many unique receptor-drug interactions that are not observed in previous GPCR structures, and answer many long standing ambiguous during drug development targeting on these receptors. In addition, our research will be of great help to the development of better drugs. Based on our previous results, we are planning to solve the structure of purinergic receptors in complex with other drugs to further understand the detailed receptor-drug interaction. We also plan to solve the structure of other GPCRs involving in the important diseases. By achieving these successes, we will provide essential insights for the regulation mechanisms of GPCRs in human diseases and benefit the future development of improved drug candidates.