Research Interests

• Chromatin structure and the associated gene activity are directed by many different chromatin regulators that are involved in chromatin modifications. The coordinated functions of chromatin regulators allow the dynamic regulation of gene activity states in diverse physiological processes. More and more chromatin regulators have been implicated in human disease pathogenesis. Thus, studying the structural basis for chromatin regulation not only helps understand the molecular mechanisms underlying the epigenetic regulation of gene activity, but also reveals the structural alterations of chromatin regulators in human disease and favors the development of therapeutic strategies. We’re interested in elucidating the structural basis of histone and DNA modifications at the level of nucleosome and chromatin, and uncovering the crosstalk mechanisms among the nucleosome modifications, by using the combinational structural methodology, such as X-ray Crystallography, Cryo-EM Single Particle Analysis, and Nuclear Magnetic Resonance. Our studies help understand how the chromatin structure is epigenetically regulated and how the malfunctions of the chromatin regulators are involved in the pathogenesis of human diseases. Our research also reveals potential drug targets for therapy development.

Education and Work Experience

• 2000-2004 B.S. in Biotechnology, Shandong University, Jinan, China

• 2004-2009 Ph.D. in Biology, Tsinghua University, Beijing, China

• 2009-2014 Postdoctoral Research Associate, Department of Biological Chemistry, University of Michigan, Howard Hughes Medical Institute, Ann Arbor, MI, USA

• 2014-2017 Professor, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

• 2017 till now Professor, Shanghai Institute of Precision Medicine, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Selected Publications

1. Xue, H., Yao, T., Cao, M., Zhu, G., Li, Y., Yuan, G., Chen, Y., Lei, M. & Huang, J. Structural basis of nucleosome recognition and modification by MLL methyltransferases. Nature 573, 445-449 (2019)

2. Yao, T., Jing, W., Hu, Z., Tan, M., Cao, M., Wang, Q., Li, Y., Yuan, G., Lei, M. & Huang, J. Structural basis of the crosstalk between histone H2B monoubiquitination and H3 lysine 79 methylation on nucleosome. Cell Res. 29, 330-333 (2019)

3. Wang, K., Yin, C., Du, X., Chen, S., Wang, J., Zhang, L., Wang, L., Yu, Y., Chi, B., Shi, M., Wang, C., Reed, R., Zhou, Y., Huang, J. & Cheng, H. A U2-snRNP–independent role of SF3b in promoting mRNA export. Proc. Natl. Acad. Sci. 116, 7837–7846 (2019)

4. Wang, X., Kang, J.-Y., Wei, L., Yang, X., Sun, H., Yang, S., Lu, L., Yan, M., Bai, M., Chen, Y., Long, J., Li, N., Li, D., Huang, J., Lei, M., Shao, Z., Yuan, W., Zuo, E., Lu, K., et al. PHF7 is a novel histone H2A E3 ligase prior to histone-to-protamine exchange during spermiogenesis. Development (2019). doi:10.1242/dev.175547

5. Xie, X., Hu, H., Tong, X., Li, L., Liu, X., Chen, M., Yuan, H., Xie, X., Li, Q., Zhang, Y., Ouyang, H., Wei, M., Huang, J., Liu, P., Gan, W., Liu, Y., Xie, A., Kuai, X., Chirn, G. W., et al. The mTOR–S6K pathway links growth signalling to DNA damage response by targeting RNF168. Nat. Cell Biol. 20, 320-331 (2018).

6. Li M, Gou H, Tripathi B, Huang J, Jiang S, Dubois W, Waybright T, Lei M, Shi J, Zhou M, Huang J. An Apela RNA-containing negative feedback loop regulates p53-mediated apoptosis in embryonic stem cells. Cell Stem Cell 16, 669-83 (2015)

7. Huang J, Brown A, Wu J, Xue J, Bley C, Rand D, Wu L, Zhang R, Chen J, Lei M. Structural basis for protein-RNA recognition in telomerase. Nat Struct Mol Biol 21, 507-12 (2014).

8. Zhou H, Liu L, Huang J, Bernard D, Karatas H, Navarro A, Lei M, Wang S. Structure-based design of high-affinity macrocyclic peptidomimetics to block the Menin-Mixed Lineage Leukemia 1 (MLL1) protein-protein interaction. J Med Chem 56, 1113-23 (2013)

9. Huang J, Wan B, Wu L, Yang Y, Dou Y, Lei M. Structural insight into the regulation of MOF in the male-specific lethal complex and the non-specific lethal complex. Cell Res. 6, 1078-81 (2012)

10. Huang J, Gurung B, Wan B, Matkar S, Veniaminova NA, Wan K, Merchant JL, Hua X, Lei M. The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature 482, 542-6 (2012)

11. Thiel AT, Huang J, Lei M, Hua X. Menin as a hub controlling mixed lineage leukemia. Bioessays 34, 771-80 (2012)

12. Zeng Z, Min B, Huang J, Hong K, Yang Y, Collins K, Lei M. Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA. Proc Natl Acad Sci U S A 108, 20357-61 (2011)