李刚课题组长期致力于“基于化学标记的功能蛋白质组学研究”，主要研究方向包括：

1）开发邻近标记、化学交联质谱等蛋白质组学平台，进行蛋白蛋白相互作用研究，鉴定泛素连接酶以及去泛素化酶的作用底物，探索肿瘤治疗的泛素化修饰蛋白新靶点。

2）开发功能氨基酸（如组氨酸、精氨酸等）的全蛋白质组修饰方法，为无法成药蛋白寻找新的共价配体，并利用配体研究RNA结合蛋白的功能。

开发“小分子分子库”对“蛋白质组”的“分子库-对-分子库”筛选平台，以超高通量快速筛选蛋白酶（如激酶、水解酶、去泛素化酶等）的抑制剂分子，以及靶向功能氨基酸的共价配体。

近期代表性论:

Yansheng Zhai, Xinyu Zhang, Zijing Chen, Dingyuan Yan, Lin Zhu, Zhe Zhang, Xianghe Wang, Kailu Tian, Yan Huang, Xi Yang, Wen Sun, Dong Wang, Yu-Hsuan Tsai , Tuoping Luo, & Gang Li*, Global profiling of functional histidines in live cells using small molecule photosensitizer and chemical probe relay labeling, Nat. Chem. 2024, accepted.

Yansheng Zhai#, Xiaoyan Huang#, Keren Zhang, Yuchen Huang, Yanlong Jiang, Jingwei Cui, Zhe Zhang, Cookson Chiu, Weiye Zhong, Gang Li*, Spatiotemporal-resolved protein networks profiling with photoactivation dependent proximity labeling, Nat. Commun. 2022, 13, 4906.

Shaoshuai Xie, Gang Li*, A key to unlock ubiquitin ligase function, Nat. Chem. Biol. 2024, DOI : 10.1038/s41589-024-01591-8 (Invited News&Views).

Gang Li, Mark A. Eckert, Jae W. Chang, Jeffrey E. Montgomery, Agnieszka Chryplewicz, Ernest Lengyel, Raymond E. Moellering*, Ultrasensitive, multiplexed chemoproteomic profiling with soluble activity-dependent proximity ligation, Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 21493. 

Gang Li, Jeffrey E. Montgomery, Mark A. Eckert, Jae W. Chang, Sam M. Tienda, Ernest Lengyel, Raymond E. Moellering* , An activity-dependent proximity ligation platform for spatially resolved quantification of active enzymes in single cells, Nat. Commun. 2017, 8, 1775. 

Gang Li, Ying Liu, Yu Liu, Li Chen, Siyu Wu, Yang Liu, Xiaoyu Li*, Photoaffinity labeling of small-molecule-binding proteins by DNA-templated chemistry, Angew. Chem. Int. Ed. 2013, 52, 9544. 

Gang Li#, Wenlu Zheng#, Zitian Chen#, Yu Zhou, Yu Liu, Junrui Yang, Yanyi Huang, Xiaoyu Li* , Design,