申请人主要从事蛋白质泛素化及降解异常调控肿瘤发生发展及药物反应的分子机制研究。近五年主要学术成绩包括：1）发现HACE1介导的胞内泛素化信号，调控自噬依赖的蛋白质降解并抑制肿瘤的机制；2）阐明铁过载加速p53降解促进肿瘤发生以及降铁化疗药物通过阻止p53蛋白降解而选择性抑制肿瘤的分子机制，有利于指导肿瘤个性化治疗；3）建立和应用原创性的研究蛋白质降解组学的工具，探讨化疗药物Bortezomib作用机制和肿瘤对其产生耐药性的分子基础，为发展药物联用方案克服肿瘤耐药性提供新思路。在Cancer Cell、Cell Reports、Cell Research等杂志发表独立或共同通讯作者研究论文7篇,获Science Signaling等专评;获国际专利授权1项，申请2项，现已进入PCT。博士后期间从事蛋白质泛素信号基础研究。在Nature等发表论文5篇，获广泛专评。今后拟继续深入开展相关研究。

Deregulated proteostasis (protein homeostasis), caused by perturbed ubiquitin signaling and proteolysis, is a main feature and leading cause of pathogenesis and development of human tumors. Changes in proteostasis also critically underlie tumor response to drug treatment. My research has mainly focused on ubiquitin (Ub) signaling and regulated proteolysis, two major aspects of proteostasis that are closely associated with tumorigenesis and tumor response to chemotherapy. Since my own lab was started about five years ago, we have made the following major discoveries or progress: 1) E3 Ub ligase HACE1,whose gene is often mutated or silenced in human tumors, ubiquitylates autophagy receptor OPTN to activate autophagy and suppress tumor; 2)mechanistic understanding of how iron overload accelerates p53 degradation and iron deprivation only suppresses tumor of wild-type p53 signaling，which would significantly help achievepersonalized therapy; 3)the molecular basis underlying tumor response to chemotherapeutic drug and proteasome inhibitor Bortezomib, by developing and applying a systems biology tool (ProTA) to quantitatively profile human protein degradome. As the solo- or co-corresponding author, we have totally published 7 papers in top scientific journals such as Cancer Cell, Cell Reports, Cell Research, etc., which were selected as Editor’s highlights or subjects for special comments. Currently, we are holding three patents, one internationally approved and two in pending. This is preceded by my postdoctoral study on the fundamental aspects of Ub signaling, which had resulted in 5 major publications, including one as research article in Nature, that have attracted wide attentions from the scientific community. In the next years to come, we are to proceed in the current course for deeper mechanistic understanding and more translational research to help achieve precision therapy for tumor patients.