(1） Development of chemical proteomics approaches for the identification and characterization of protein-protein interactions mediated by histone and non-histone modifications 

(2) Development and biological activity evaluation of inhibitors targeting protein-protein interactions 

(3) Target identification of bioactive small molecules, peptides, and natural products

(4) Mapping the proteome-wide ligandability of drug-like fragments

The research of Dr. Xin Li focuses on the development of chemical tools and methods to resolve the biological significance of histone epigenetic modifications and explore new strategies to target abnormal histone modifications for disease treatment. His main academic achievements include: (1) the development and application of a universal chemical proteomics platform that enables the identification and functional characterization of crotonylation and other modifications-mediated interaction networks to elucidate their regulatory mechanisms and biological significance; the development of the first-in-class YEATS domain inhibitors with anticancer activity, providing a series of lead compounds for drug discovery campaigns targeting the YEATS domain; and the development of the first method to evaluate the activity of bromodomain inhibitors in living cells, facilitating the further development of bromodomain inhibitors. Dr. Li has published more than 20 papers in Nat. Chem. Biol., J. Am. Chem. Soc., Nat. Commun., Acc. Chem. Res., etc.

X. Li, X.-M. Li, Y. Jiang, Z. Liu, Y. Cui, K. Y. Fung, S. H. E. van der Beelen, G. Tian, L. Wan, X. Shi, C. D. Allis, H. Li, Y. Li*, X. D. Li*, Structure-guided development of YEATS domain inhibitors by targeting -- stacking. Nat. Chem. Biol., 2018, 14, 1140-1149.

X. Li, Y. Wu, G. Tian, Y. Jiang, Z. Liu, X. Meng, X. Bao, L. Feng, H. Sun, H. Deng, X. D. Li*, Chemical proteomic profiling of bromodomains enables the wide-spectrum evaluation of bromodomain inhibitors in living cells. J. Am. Chem. Soc., 2019, 141, 11497-11505.

X. Li, X. D. Li*, Integrative chemical biology approaches to deciphering the histone code: a problem-driven journey. Acc. Chem. Res., 2021, 54, 3734-3747.

X. Li*, S. Liu; X. Li, X. D. Li*, YEATS domains as novel epigenetic readers: structures, functions, and inhibitor development. ACS Chem. Biol., 2023, 18, 994-1013.

A. Zhu#, X. Li#, L. Bai#, G. Zhu, Y. Guo, J. Lin, Y. Cui, G. Tian, L. Zhang, J. Wang, X. D. Li*, L. Li*, Biomimetic -selective ribosylations enable two-step modular syntheses of biologically important ADP-ribosylated peptides. Nat. Commun., 2020, 11, 5600. (#equally contributed)

Y. Jiang, G. Chen, X.-M. Li, S. Liu, G. Tian, Y. Li*, X. Li*, H. Li*, X. D. Li*, Selective targeting of AF9 YEATS domain by cyclopeptide inhibitors with preorganized conformation. J. Am. Chem. Soc., 2020, 142, 21450-21459. 

Y. Zhou, L. Chen, J. Peng, L. Xie, L. Meng, Q. Li, J. Zhang, X. D. Li, X. Li*, X. Huang*, X. Li*, DNA-encoded dynamic chemical library and its applications in ligand discovery. J. Am. Chem. Soc., 2018, 140, 15859-15867.

S. Liu; X. Li, X. Li*, X. D. Li*, Recent advances in the development of peptide-based inhibitors targeting epigenetic readers of histone lysine acetylation and methylation marks. Curr. Opin. Chem. Biol., 2023, 75, 102334.

X. Bao#, Y. Wang#, X. Li#, X.-M. Li#, Z. Liu, T. Yang, C. F. Wong, J. Zhang, Q. Hao, X. D. Li*, Identification of ‘erasers’ for lysine crotonylated histone marks using a chemical proteomics approach. eLife, 2014, 3. (#equally contributed)

X. Li, X. D. Li*, Chemical proteomics approaches to examine novel histone posttranslational modifications. Curr. Opin. Chem. Biol., 2015, 24, 80-90.