I am interested in studying mechanisms of macromolecular machines that play fundamental roles in cell fate determination by multi-disciplinary approaches. Most proteins form a network of interactions with other proteins and many are components of large complexes in vivo. We focus on those which play fundamental roles within the cell and aim to establish fundamental principles underlying the assembly of multi-protein complexes, define their structures, gain insight into their mechanisms using cryo-electron microscopy and x-ray crystallography. In the past, we have been successfully applied this hybrid approach to various macromolecular machines including proteasome, E3 ubiquitin ligase and DNA replication complex. We are now implementing these technologies to investigating fundamental mechanism of cell fate determination. We are also developing cutting-edge methodologies that can faithfully image the native cellular environment at high-resolution, aiming to reveal a complete structural description of the cell's native molecular landscape at certain stage.
Research Areas
Biochemistry & Molecular biology
Structural biology
Genetics
Education
2008-2012 The Institute of Cancer Research/Ph.D
2002-2006 Tsinghua University/B.S
Experience
2018-present Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences/Principal Investigator
2016-2018 UCB Pharma/Senior Scientist
2013-2016 The Clare Hall Laboratories, the Francis Crick Institute/Post-doctoral Research Fellow
2012-2013 The Institute of Cancer Research/Post-doctoral Scientist
Publications
1. Dong, S. #, Li, H. #, Wang, M. #, Rasheed, N. #, Zou, B., Gao, X., Guan, J., Li, W., Zhang, J., Wang, C., Zhou, N., Shi, X., Li, M., Zhou, M., Huang, J., Li, H., Zhang, Y., Wong, K.H., Zhang, X., Chao, W.C.H.*, and He, J*. Structural basis of nucleosome deacetylation and DNA linker tightening by Rpd3S histone deacetylase complex. Cell Res 33, 790-801. (2023)
2. Zhang, X. #, Li, Z. #, Zhang, Y. #, Liu, Y. #, Wang, J., Liu, B., Chen, Q., Wang, Q., Fu, L., Wang, P., Zhong, X., Jin, L., Yan, Q., Chen, L., He, J.*, Zhao, J. *, and Xiong, X*. Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes. Life Sci Alliance 6. (2023)
3. Yu, H. #, Liu, B. #, Zhang, Y. #, Gao, X. #, Wang, Q. #, Xiang, H. #, Peng, X. #, Xie, C. #, Wang, Y. #, Hu, P., Shi, J., Shi, Q., Zheng, P., Feng, C., Tang, G., Liu, X., Guo, L., Lin, X., Li, J., Liu, C., Huang, Y., Yang, N., Chen, Q., Li, Z., Su, M., Yan, Q., Pei, R., Chen, X., Liu, L., Hu, F., Liang, D., Ke, B., Ke, C. *, Li, F. *, He, J. *, Wang, M.*, Chen, L.*, Xiong, X.*, and Tang, X*. Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants. Nat Commun 14, 1058. (2023)
4. Tang, L. #, Dong, S. #, Rasheed, N. #, Wu, H.W. #, Zhou, N. #, Li, H., Wang, M., Zheng, J.*, He, J.*, and Chao, W.C.H*. Vibrio parahaemolyticus prey targeting requires autoproteolysis-triggered dimerization of the type VI secretion system effector RhsP. Cell Rep 41, 111732. (2022)
5. He, P. #, Liu, B. #, Gao, X. #, Yan, Q. #, Pei, R. #, Sun, J., Chen, Q., Hou, R., Li, Z., Zhang, Y., Zhao, J., Sun, H., Feng, B., Wang, Q., Yi, H., Hu, P., Li, P., Zhang, Y., Chen, Z., Niu, X., Zhong, X., Jin, L., Liu, X., Qu, K., Ciazynska, K.A., Carter, A.P., Briggs, J.A.G., Chen, J., Liu, J., Chen, X.*, He, J.*, Chen, L.*, and Xiong, X*. SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope. Nat Microbiol 7, 1635-1649. (2022)
6. Chen, M. #, He, Y. #, Liu, D., Tian, L., Xu, P., Liu, X., Pan, Y., Dong, S., He, J. *, and Zhang, Y*. Structure Insights Into Photosystem I Octamer From Cyanobacteria. Front Microbiol 13, 876122. (2022)
7. Chen, M. #, Liu, X., He, Y., Li, N., He, J.*, and Zhang, Y*. Diversity Among Cyanobacterial Photosystem I Oligomers. Front Microbiol 12, 781826. (2021)
8. Frigola, J. #, He, J. #, Kinkelin, K., Pye, V.E., Renault, L., Douglas, M.E., Remus, D., Cherepanov, P. *, Costa, A. *, and Diffley, J.F.X*. Cdt1 stabilizes an open MCM ring for helicase loading. Nat Commun 8, 15720. (2017)
9. He, J. #, Chao, W.C. #, Zhang, Z., Yang, J., Cronin, N., and Barford, D*. Insights into degron recognition by APC/C coactivators from the structure of an Acm1-Cdh1 complex. Mol Cell 50, 649-660. (2013)
10. He, J. #, Kulkarni, K., da Fonseca, P.C., Krutauz, D., Glickman, M.H., Barford, D.*, and Morris, E.P*. The structure of the 26S proteasome subunit Rpn2 reveals its PC repeat domain as a closed toroid of two concentric alpha-helical rings. Structure 20, 513-521. (2012)
11. Zhang, C. #, Li, L., He, J., Chen, C., and Su, D*. Nonstructural protein 7 and 8 complexes of SARS-CoV-2. Protein Sci 30, 873-881. (2021)
12. Zhang, C. #, Chen, Y., Li, L., Yang, Y., He, J., Chen, C. *, and Su, D*. Structural basis for the multimerization of nonstructural protein nsp9 from SARS-CoV-2. Mol Biomed 1, 5. (2020)
13. da Fonseca, P.C. #, He, J., and Morris, E.P*. Molecular model of the human 26S proteasome. Mol Cell 46, 54-66. (2012)
14. Wang, X. et al. A potent human monoclonal antibody with pan-neutralizing activities directly dislocates S trimer of SARS-CoV-2 through binding both up and down forms of RBD. Signal Transduct Target Ther 7, 114. (2022)
15. Qu, K. #, Chen, Q., Ciazynska, K.A., Liu, B., Zhang, X., Wang, J., He, Y., Guan, J., He, J., Liu, T., Zhang, X., Carter, A.P., Xiong, X.*, and Briggs, J.A.G*. Engineered disulfide reveals structural dynamics of locked SARS-CoV-2 spike. PLoS Pathog 18, e1010583. (2022)
16.Zhang, X.#, Xin, J.#, Wang, Z.#, Wu, W., Liu, Y., Min, Z., Xin, Y., Liu, B., He, J., Zhang, X., and Xu, X*. Structural basis of a bi-functional malonyl-CoA reductase (MCR) from the photosynthetic green non-sulfur bacterium Roseiflexus castenholzii. mBio14, e0323322. (2023)
Students
已指导学生
邹彬倩 硕士研究生 085238-生物工程
现指导学生
张家乐 博士研究生 071010-生物化学与分子生物学
董淑琦 博士研究生 071010-生物化学与分子生物学
赵河豫 博士研究生 071010-生物化学与分子生物学
苏小凤 硕士研究生 086000-生物与医药
罗窍鸿 硕士研究生 086000-生物与医药
Honors & Distinctions
2020 Huangpu Talent Program, Guangzhou City
2018 High-Level Talent Program, Chinese Academy of Sciences
2013 Chairman’s Prize for Best PhD, the Institute of Cancer Research
2012 Government Award for outstanding students abroad