肿瘤微环境对肿瘤发生发展极为重要，是肿瘤精准治疗的重要研究方向。申请人近年来集中研究了肿瘤微环境的调控机制，发现泛素化修饰在肿瘤细胞与微环境中起重要作用。原创性学术成果：1）发现动态泛素化修饰是外界营养调控mTORC1信号通路的重要机制：阐明了营养匮乏导致RagA的多泛素化修饰是调控mTORC1的重要分子刹车，揭示了SUMO化调控AKT1活化以及泛素化调控c-Myc蛋白稳定性的多重机制；2）发现了泛素依赖及非依赖的蛋白降解调控炎症关键通路的新机制；3）揭示泛素依赖的KLF2降解对血管新生的关键作用。自获得优青以来，以通讯作者在Mol Cell、Cell Res、Cell Rep、Cancer Res、Oncogene等国际学术期刊发表论文9篇，平均影响因子8.5。全部论文被Nature、Cell等引用890余次。申请人先后获得教育部“新世纪人才”、上海市“曙光学者”等称号。

Tumor microenvironment is essential for tumorigenesis and cancer development. Identification of the underlying mechanism of tumor microenvironment is one the most important field for precise cancer treatment. In the past years, the applicant has been focused on the regulation of tumor microenvironment by ubiquitination signal. His study indicated that the dynamic ubiquitination and deubiquitination functions as important molecular codes to regulate the tumor microenvironment and cancer cells. These findings have significant impact on the understanding of tumor microenvironment and development of novel therapeutic strategies. The applicant’s major contributions includes: 1) identified that the dynamic ubiquitination of RagA negatively regulates the mTORC1 pathway mediated by cellular nutrition and found RNF152 is a specific E3 ligase for RagA; clarified that the critical role of AKT SUMOylation in cancer cell proliferation and identified multiple regulatory mechanisms for c-Myc ubiquitination in tumorigenesis; 2) found the important role of ubiquitination in inflammation; 3) uncovered that angiogenesis is regulated by FBW7 mediated KLF2 degradation. Since he got the support of National Science Funds for Excellent Young Scholars, he has published 9 research articles as corresponding author in high profile journals, such as Molecular Cell, Cell Res, Cell Rep，Cancer Res, and Oncogene etc. The average impact factor of these papers is 8.5. All his publications have been cited for around 890 times by others in the past years. His lab will continue to study the regulatory mechanism of tumor microenvironment by ubiquitination.