• Chemical proteomics and epigenetics
• Regulation and function of histone modifications
• Chemical biology approaches to identify epigenetic ‘readers’, ‘erasers’ and ‘writers’
• Protein target identification of small molecules (i.e., drug target I.D.) and mapping drug binding sites.

• B.Sc. in Chemistry, Fudan University (1999-2003)
• Ph.D. in Organic and Bioorganic Chemistry, The University of Hong Kong, with Prof. Dan Yang (2003-2008)
• Postdoctoral Fellow in Chemical Biology, The Rockefeller University, New York, USA, with Professor Tarun M. Kapoor (2008-2011)

• Professor, Department of Chemistry, HKU (From 2020 to present)
• Professor (by courtesy), School of Biological Science, HKU (From 2021 to present)

My lab is at the interface of chemistry and biology, with a focus on developing chemical biology approaches to study epigenetics. Epigenetics is an emerging field that explores the combined effects of genetics and the environment on our health. It plays a crucial role in understanding various human diseases, including cancer and developmental abnormalities. The development of epigenetic therapies is at the forefront of drug discovery. However, there is still much to learn about the complex mechanisms through which epigenetics regulates cellular processes. One area of interest is the influence of histone proteins, which package our genetic material (DNA) and are believed to impact a wide range of epigenetic processes. Histones can undergo chemical modifications through the addition of small chemical groups. These modifications create a chromatin modification landscape, both locally and globally, which is thought to form a "code" known as the histone code. This code plays a crucial role in regulating various DNA-associated processes, including gene expression. However, for many of these modifications, we do not know how they are put on (‘written’) or taken off (‘erased’) from histones, and how they are ‘translated’ for signaling downstream cellular processes. To fill this knowledge gap, Prof. Li’s research aims at deciphering histone code using chemical biology approaches by combining chemistry, biochemistry, biophysics, cell biology and state-of-the-art mass spectrometry technology.

Over the past decade, our lab has identified novel "readers", "writers" and "erasers" of the histone code that were previously unknown to be involved in epigenetic regulation through histone modifications. This research has shed light on the biological roles of specific histone modifications and their implications in normal physiology and disease pathogenesis.

Through our future studies, we aim to unravel the mechanisms that govern the interpretation of the histone code. We hope to shed light on the intricate interplay between histone modifications and various cellular processes. This endeavor will contribute to a better understanding of the complex regulatory mechanisms that govern gene expression and other essential biological processes.

1. J. Lin, Y. Wu, G. Tian, D. Yu, E. Yang, W. H. Lam, Z. Liu, Y. Jing, S. Dang, X. Bao, J. W. H. Wong, Y. Zhai, X. D. Li, “Menin "reads" H3K79me2 mark in a nucleosomal context”, Science, 2023, 379, 717-723.

2. Z. Liu, Y. Wu, K. C. J. Kwan, X. Cheng, X. Li, Y. Jing, X. D. Li, “Development of multifunctional synthetic nucleosomes to interrogate chromatin-mediated protein interactions”, Sci Adv., 2023, 9, eade5186.

3. X.-M. Li, S. Huang, X. D. Li, “Photo-ANA enables profiling of host-bacteria protein interactions during infection”, Nat. Chem. Biol., 2023, 19, 614.

4. J. Lin, X. Bao, X. D. Li, “A tri-functional amino acid enables mapping of binding sites for posttranslational-modification-mediated protein-protein interactions”, Mol. Cell, 2021, 81, 2669-2681.e9.

5. 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.

6. X. Bao, Z. Liu, W. Zhang, K. Gladysz, Y. M. E. Fung, G. Tian, Y. Xiong, J. W. H. Wong, K. W. Y. Yuen, X. D. Li, “Glutarylation of histone H4 lysine 91 regulates chromatin dynamics”, Mol. Cell, 2019, 76, 660-675.e9.

7. 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.

8. 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 π-π-π stacking”, Nat. Chem. Biol., 2018, 14, 1140-1149.

9. T. Yang, X.-M. Li, X. Bao, Y. M. E. Fung, X. D. Li, “Photo-lysine captures proteins that bind lysine posttranslational modifications”, Nat. Chem. Biol., 2016, 12, 70-72.

10. 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, e02999.

1. Areas of Excellence Scheme (AoE), $HKD 49,689,000, PC (since 2021), Chemical biology approach to molecular medicine, 2017-2025.
2. Collaborative Research Fund (CRF), $HKD 8,550,000, PC, Development of Chemical Probes for YEATS2 and Their Uses in Mechanistic and Pharmacological Studies, 2023-2026.
3. Collaborative Research Fund (CRF), $HKD 7,508,902, PC, Integrative chemical biology approaches to decipher histone marks on H3K79, 2020-2023.
4. Collaborative Research Fund (CRF), $HKD 5,820,261, PC, Regulation and Function of Novel Histone Modifications, 2016-2019.
5. General Research Fund (GRF), $HKD 877,079, PI, Development of Genetically Encoded Chemical Probes for YEATS Domains, 2023-2026.
6. General Research Fund (GRF), $HKD 799,000, PI, Development of Chemical Proteomic Approaches to Interrogate the Interplay of Histone and DNA Methylation Marks, 2022-2025.
7. General Research Fund (GRF), $HKD 1,170,20, PI, Developing bioorthogonal and photo-cross-linkable amino acids for identification of cell-type-specific protein-protein interactions in physiological context, 2021-2023.
8. General Research Fund (GRF), $HKD 1,150,080, PI, Chemical tools for identification and interrogation of ‘readers’ of histone crotonylation, 2018-2021.
9. General Research Fund (GRF), $HKD 1,069,178, PI, The regulation of chromatin structure and dynamics by histone glutarylation, 2017-2020.
10. National Natural Science Foundation of China (NSFC), $HKD 1,540,795, PI, NSFC Excellent Young Scientist Fund (Hong Kong and Macau)(国家优秀青年科学基金项目（港澳）), 2020-2022.
11. National Natural Science Foundation of China (NSFC), $HKD 906,120, PI, Examining the influences of histone succinylation on nucleosome/chromatin structure and dynamics and identification of readers of histone succinylation(组蛋白琥珀酰化对核小体和染色质动态结构影响的表征及其阅读器的鉴定), 2018-2020.
12. National Natural Science Foundation of China (NSFC), $HKD 816,400, PI, Chemical proteomics approach to examine histone arginine methylation (发展化学蛋白组学方法以研究组蛋白精氨酸甲基化，面上项目), 2016-2019.

• Outstanding Researcher Award 2023/24, The University of Hong Kong (2024)
• Tetrahedron Young Investigator Award for Bioorganic and Medicinal Chemistry (2023)
• Member of the Hong Kong Young Academy of Sciences (YASHK) (2021)
• NSFC Excellent Young Scientists Award (Hong Kong and Macau), China (2019)
• CAPA Distinguished Faculty Award from Chinese-American Chemistry & Chemical Biology Professors Association (CAPA), USA (2018)
• The Distinguished Lectureship Award from The Chemical Society of Japan (2018)
• Outstanding Young Researcher Award 2015/16, The University of Hong Kong (2016)
• Early Career Award from the Hong Kong Research Grant Council (RGC) (2013)

• Dr. Gaofei TIAN (Postdoctoral Researcher)
• Dr. Siyue HUANG (Postdoctoral Researcher)
• Dr. Guixin PENG (Postdoctoral Researcher)
• Dr. Yinqiao WU (Postdoctoral Researcher)
• Dr. Sha LIU (Postdoctoral Researcher)
• Dr. Daqi YU (Postdoctoral Researcher)
• Ka Chun KWAN, Jonathan (Graduate Student)
• Derui LI (Graduate Student)
• Xiang LI (Graduate Student)
• Wanzhang ZHANG (Graduate Student)
• Min XU (Graduate Student)
• Xin MAO (Graduate Student)
• Siqin YU (Graduate Student)
• Yuzhen DING (Graduate Student)
• Shuai LV (Graduate Student)
• Xinyu DONG (Graduate Student)
• Zelin ZHOU (Graduate Student)