Our group focuses on developing novel approaches to reverse epigenetic and transcriptional abnormalities for cancer therapy by combining a variety of biological and chemical strategies. Specifically, we are interested in the following areas:

1. What are the molecular mechanisms by which dysregulated epigenetic modulators or transcription factors drive tumor progression?

2. How can we develop therapeutic agents (e.g., small molecules, mRNA-based and immune cell-based therapy) to target abnormal epigenetic modifications or transcriptional programs in cancer cells?

3. How can we identify biomarkers to personalize epigenetic therapies for cancer patients?

Patents

PCT/CN2023/073678

CN118360251A

CN117618571A

CN117045801A

CN105560219B

CN105078983A

CN2024111905044

2019, AACR-Scholar in Training Award

1.  Kong X^#, Chen J^#, Xie W^#, Brown S, Cai Y, Wu K, Fan D, Nie Y, Yegnasubramanian S, Tiedemann R, Tao Y, Yen R, Topper MJ, Easwaran H, Rothbart SB*, Xia L*, Baylin SB*, Defining UHRF1 Domains That Support Maintenance of Human Colon Cancer DNA Methylation and Oncogenic Properties, Cancer Cell. 2019;35(4):633-648

2.  Chang Y^#, Guo H^#, Li X^#, Zong L, Wei J, Li Z, Luo C, Yang X, Fang H, Kong X*, Hou X*, Development of a First-in-Class DNMT1/HDAC Inhibitor with Improved Therapeutic Potential and Potentiated Antitumor Immunity, J Med Chem. 2024; 67(18):16480-16504.

3.  Zhang H^#, Xu D^#, Huang H^#, Jiang H, Hu L, Liu L, Sun G, Gao J, Li Y, Xia C, Chen S, Zhou H, Kong X*, Wang M*, Luo C*, Discovery of a Covalent Inhibitor Selectively Targeting the Autophosphorylation Site of c-Src Kinase, ACS Chem Biol. 2024;19(4):999-1010.

4.  Li P, Xia C, Kong X*, Zhang J*, Enhancing nicotinamide N-methyltransferase bisubstrate inhibitor activity through 7-deazaadenosine and linker modifications, Bioorg Chem. 2024;143:106963.

5.  Zhu C, Liu J, Ni Y, Chen W, Rong W, Zhang X, Guo C, Kong X*, Tang S*, Synthesis of STM2457, a selective small-molecule inhibitor of METTL3, Tetrahedron Lett. 2024; 141, 155077

6.  Li E, Wang K, Zhang B, Guo S , Xiao S , Pan Q , Wang X , Chen W , Wu Y , Xu H, Kong X*, Luo C, Chen S*, Liu B*, Design, synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties, J Enzyme Inhib Med Chem. 2022;37(1):1537-55

7.  Kong X^#, Liu J^#, Li L, Yue L, Zhang L, Jiang H, Xie X*, Luo C*, Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition, Nucleic Acids Res. 2015;43(9):4381-92

8.  Kong X^#, Chen L^#, Jiao L, Jiang X, Lian F, Lu J, Zhu K, Du D, Liu J, Ding H, Zhang N, Shen J, Zheng M, Chen K, Liu X, Jiang H, Luo C*. Astemizole arrests the proliferation of cancer cells by disrupting the EZH2-EED interaction of polycomb repressive complex 2, J Med Chem. 2014;57(22):9512-21

9.  Ye F^#, Kong X^#, Zhang H, Liu Y, Shao Z, Jin J, Cai Y, Zhang R, Li L, Zhang YW, Liu YC, Zhang C, Xie W, Yu K, Ding H, Zhao K, Chen S*, Jiang H, Baylin SB*, Luo C*. Biochemical Studies and Molecular Dynamic Simulations Reveal the Molecular Basis of Conformational Changes in DNA Methyltransferase-1, ACS Chem Biol. 2018;13(3):772-781