Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

Dr. ZHANG Naixia graduated from Beijing Medical University in 1998, and got a Bachelor’s degree with the major in medicinal chemistry. In the same year, Dr. ZHANG got admitted into the PhD training program at Shanghai Institute of Organic Chemistry, and got the PhD degree in 2003. In May of 2004, Dr. ZHANG joined Dr. Kylie Walters’ lab in the Department of Biochemistry, Molecular Biology, and Biophysics at the University of Minnesota as a postdoctoral fellow, and was then promoted to research assistant professor in 2008. In October of 2010, Dr. ZHANG Naixia joined Shanghai Institute of Materia Medica, Chinese Academy of Sciences as a principal investigator. Dr. ZHANG’s major research interests focus on NMR studies of protein-ligand (protein, DNA, small molecule etc.) interactions, and have made excellent achievements in quite a few of research projects. Up to now, Dr. ZHANG Naixia has published more than 100 research articles.

Education Experience：

1994.09 - 1998.07, Bachelor degree, Medicinal Chemistry, Beijing Medical University

1998.09 - 2003.07, PhD degree, Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences

Work Experience：

2004.05 - 2008.06, Postdoctoral Fellow, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA

2008.06 - 2010.02, Research Assistant Professor, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA

2010.10 - up to now, Research Professor & Principal Investigator, Analytical Research Center for Organic and Biological Molecules & Institutional Center for Shared Technologies and Facilities of SIMM, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

Research Directions

1.NMR studies of protein-protein interactions;

2.NMR studies of drug target (protein)-small molecule interactions.

Grants & Research Projects

1.National Natural Science Foundation of China, Discovery of agonists targeting deubiquitinating enzyme USP7 and exploration of their working mechanisms, Project leader, 2025.01-2028.12

2.National Natural Science Foundation of China, Structure and function studies of human co-chaperone Aha1, Project leader, 2022.01-2025.12

3.National Natural Science Foundation of China, Discovery of novel type of anti-cancer inhibitors targeting USP28 catalytic domain and their working mechanism elucidation, Project leader, 2020.01-2023.12

4.National Natural Science Foundation of China, Discovery of novel anti-cancer inhibitors targeting Hsp90 middle domain and their working mechanism elucidation, Project leader, 2018.01-2021.12

5.National Natural Science Foundation of China, ATP-dependent conformational changes of Hsp90 and drug discovery, Project leader, 2013.01-2016.12

Achievements

1.Molecular mechanism studies of substrate capture process of ubiquitin-proteasome protein degradation pathway;

2.Functional regulatory mechanism analysis and chemical intervention studies of deubiquitinating enzymes such as USP28, USP25, and USP7 etc.;

3.Mechanistic analysis and chemical intervention studies of the Hsp90-Aha1 system;

4.Mechanistic studies of interactions between intrinsically disordered proteins and active compounds;

5.An NMR-based research platform for studying protein-ligand interactions;

6.An NMR-based technical platform for qualitative and quantitative analysis of compounds.

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Social Titles

1.Committee Member of Biological Magnetic Resonance Academic Subgroup, Biophysical Society of China;

2.Executive Council Member of the Magnetic Resonance Technology Alliance, Chinese Academy of Sciences;

3.Committee Member of the Protein Data Bank China Advisory Committee;

4.Editorial Board Member of Scientific Reports and Magnetic Resonance Letters.

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Awards & Honors

1.2008, Paul D. Boyer-James B. Peter Award, University of Minnesota

2.2023, Pudong District, Shanghai, Talented Engineer

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Publications

Selected Publications

1.Zhong, Y.#, Shi, L.#, Xu, Z.#, Gao, J., Ma, Q., Gao, T., Tang, J., Xiong, M., Xu, Y., Dai, H., Zhou, H., Zhang, N.*, Zhou, C.*, Benzbromarone interferes with the interaction between Hsp90 and Aha1 by interacting with both of them, Communications Biology, 8(1), 761, 2025.

2.Shi, L.#, Xu, Z.#, Chen, X., Meng, Q., Zhou, H., Xiong, B., Zhang, N.*, Sertraline and Astemizole enhance the deubiquitinase activity of USP7 by binding to its switching loop region, Journal of Medicinal Chemistry, 68(5), 5874-5890, 2025.

3.Zhou, C.#, Zhang, J.#, Luo, X.#, Lian, F., Zeng, Y., Zhang, Z., Zhang, H.*, Zhang, N.*, Sodium oligomannate electrostatically binds to Aβ and blocks its aggregation, Journal of Physical Chemistry B, 127(9), 1983-1994, 2023.

4.Xu, Z.#, Wang, H.#, Meng, Q., Ding, Y., Zhu, M., Zhou, H., Zhang, N.*, Shi, L.*, Otilonium Bromide acts as a selective USP28 inhibitor and exhibits cytotoxic activity against multiple human cancer cell lines, Biochemical Pharmacology, 215, 115746, 2023.

5.Tang, J., Hu, H., Zhou, C.*, Zhang, N.*, Human Aha1's N-terminal extension confers it holdase activity in vitro, Protein Science, 32(9), e4735, 2023.

6.Gao, J.#, Zhou, C.#, Zhong, Y.#, Shi, L., Luo, X., Su, H., Li, M., Xu, Y., Zhang, N.*, Zhou, H.*, Dipyridamole interacts with the N-terminal domain of HSP90 and antagonizes the function of the chaperone in multiple cancer cell lines, Biochemical Pharmacology, 207, 115376, 2023.

7.Zhu, M., Wang, H., Ding, Y., Yang, Y., Xu, Z., Shi, L.*, Zhang, N.*, Ribonucleotide reductase holoenzyme inhibitor COH29 interacts with deubiquitinase ubiquitin-specific protease 2 and downregulates its substrate protein cyclin D1, FASEB Journal, 36(5), e22329, 2022.

8.Wang, H., Meng, Q., Ding, Y., Xiong, M., Zhu, M., Yang, Y., Su, H., Gu, L., Xu, Y., Shi, L.*, Zhou, H.*, Zhang, N.*, USP28 and USP25 are downregulated by Vismodegib in vitro and in colorectal cancer cell lines, FEBS Journal, 288(4), 1325-1342, 2021.

9.Zhou, C.#, Zhang, C.#, Zhu, H.#, Liu, Z., Su, H., Zhang, X., Chen, T., Zhong, Y., Hu, H., Xiong, M., Zhou, H., Xu, Y.*, Zhang, A.*, Zhang, N.*, Allosteric regulation of Hsp90α's activity by small molecules targeting the middle domain of the chaperone, iScience, 23(2), 100857, 2020.

10.Yang, Y., Ding, Y., Zhou, C., Wen, Y., Zhang, N.*, Structural and functional studies of USP20 ZnF-UBP domain by NMR, Protein Science, 28(9), 1606-1619, 2019.

11.Yang, Y.#, Shi, L.#, Ding, Y., Shi, Y., Hu, H., Wen, Y.*, Zhang, N.*, Structural and functional investigations of the N-terminal ubiquitin binding region of Usp25, Biophysical Journal, 112(10), 2099-2108, 2017.

12.Yu, J.#, Chen, T.#, Zhou, C.#, Lian, F., Tang, X., Wen, Y., Shen, J., Xu, Y., Xiong, B.*, Zhang, N.*, NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds, Acta Pharmacologica Sinica, 37(7), 984-93, 2016.

13.Wen, Y.#, Shi, L.#, Ding, Y., Cui, R., He, W.T., Hu, H.*, Zhang, N.*, The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights, Biochemical Journal, 471(2), 155-65, 2015.

14.Zhang, N.#, Wang, Q.#, Ehlinger, A.#, Randles, L.#, Lary, J.W., Kang, Y., Haririnia, A., Storaska, A.J., Cole, J.L., Fushman, D., Walters, K.J.*, Structure of the S5a:K48-linked diubiquitin complex and its interactions with Rpn13, Molecular Cell, 35(3), 280-290, 2009.

15.Husnjak, K.#, Elsasser, S.#, Zhang, N.#, Chen, X., Randles, L., Shi, Y., Hofmann, K., Walters, K.J.*, Finley, D.*, Dikic, I.*, Proteasome subunit Rpn13 is a novel ubiquitin receptor, Nature, 453(7194), 481-488, 2008.

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