申请人一直致力于心血管疾病分子机制研究，在心肌细胞死亡的信号转导、微小RNA与心肌损伤、心肌梗死的发病机理等方面取得系列成果。主要成绩如下：1、发现miR-499调控心肌细胞凋亡的分子机制；2、发现miRNA氧化修饰在心肌损伤中的作用机制；3、揭示了心肌细胞程序性坏死调控机制；4、揭示了药物诱导的心肌毒性损伤中的分子机制。发表SCI论文20篇，其中以第一作者或通讯作者在Nature medicine、Circulation research、molecular cell等杂志上发表论文8篇，累计影响因子82，他引338次。拟在前期工作基础上进一步研究心肌内源性保护蛋白—Parkin在心肌细胞程序性坏死、线粒体自噬及心肌损伤中的作用机制，揭示关键调控因子及信号通路。本项研究对于丰富和完善心脏分子、细胞生物学研究具有重要的理论意义，同时将为探讨心肌梗死、心衰等心脏疾病的预防、治疗开辟新的方向。

My main scientific focus has been on molecular mechanism of cardiovascular diseases. Specifically, I have demonstrated the signaling transduction in cardiomyocytes death, miRNA in cardiac disease and the molecular mechanisms regulating myocardial infarction. The scope of my scientific works covers four interwinded programs: (1) miR-499, a muscle-specific miRNA, participates in cardioprotection through inhibiting cardiomyocytes apoptosis by targeting calcineurin and Drp1. (2) I first discovered oxidative modification of miRNA and demonstrated the regulating mechanism of oxidative modified-miRNA during cardiac injury. (3) The molecular mechanism of programmed necrosis. (4) Apoptosis in drug-induced cardiotoxicity. During the past 10 years, I published 20 papers in SCI journal of biological chemistry, among those are 8 first author or corresponding author in journal such as Nature Medicine, Molecular Cell, Circulation Research with an accumulative IF more than 80. The citation of my publications reaches XXX. In addition, I applied 2 national patents. In my future study, I propose to systematically study the the functional role and molecular mechanism of Parkin in cardiomyocytes programmed necrosis, mitophagy and cardiac injury. As a powerful cardiac protective factor, Parkin may be an important therapeutic target of heart diseases. This project not only can add incremental knowledge for cardiac molecular and cellular mechanisms but also may provide effective therapy for myocardial infarction and heart failure.