ZHUANG Youwen
Tel:( +86)-13764001814
Email: youwen_zhuang@sjtu.edu.cn
Biography:
Youwen Zhuang, Professor and Doctoral Supervisor at Shanghai Jiao Tong University School of Medicine. His research primarily focuses on elucidating the molecular pharmacological and signaling mechanisms of neurotransmitter GPCRs, along with rational drug design. The GPCRs of particular interest in his work include those crucial for the onset and progression of neuropsychiatric disorders such as Parkinson’s disease, schizophrenia, depression, and chronic pain. Professor Zhuang has published 19 papers in top-tier journals, including four papers in Cell, and others in Neuron, Nat Chem Biol, PNAS, Cell Res, etc. One of these Cell papers was selected as the cover story, and another was chosen as a featured article and ‘Best of Cell 2023’. His research has been supported by NSFC, National Key R&D Program, Science and Technology Commission of Shanghai Municipality, etc. He has been recognized by the Youth Talent Support Program of China Association for Science and Technology and the Youth Innovation Promotion Association of the Chinese Academy of Sciences. The awards and honors he achieved include MIT Technology Review Innovators Under 35 China, First Prize in Shanghai Natural Science Award, and the Sanofi Outstanding Young Scientist Award, etc.
Education:
2014 – 2020 Shanghai Institute of Materia Medica, CAS Ph. D.
2018 – 2019 Van Andel Institute, USA Visiting Scholar
2010 – 2014 Southwest University, China B.S.
Positions and Employment:
2024 – Now Shanghai Jiao Tong University PI/ Professor
2021– 2024 Shanghai Institute of Materia Medica, CAS Associate Professor
2020 – 2021 Shanghai Institute of Materia Medica, CAS Assistant Professor
Research Field:
G protein-coupled receptors (GPCRs) represent the largest superfamily of membrane proteins in humans and have emerged as the most successful drug targets to date. They play a pivotal role in various physiological processes, including sensory perception, neural signal transduction, and immune regulation. Neurotransmitter GPCRs are integral to the formation of neurotransmitter systems, and disruptions in their signaling and function are closely linked to the onset and progression of neuropsychiatric disorders such as schizophrenia and depression. Therefore, targeting neurotransmitter GPCRs in drug discovery and restoring the delicate balance of their functions and signaling pathways are essential for effectively treating these conditions. The research in Dr. Zhuang’s laboratory mainly focuses on the molecular understanding of the signaling and pharmacology of neurotransmitter GPCRs, and structure-based drug design. The GPCRs of particular interest in his work include those crucial for neuropsychiatric conditions, such as dopamine receptors, opioid receptors, and cannabinoid receptors.
Publications (# First author, * Corresponding author):
Zhuang, Y.#,*, Wang, Y.#, He, B.#, He, X.#, Zhou, X. E., Guo, S., Rao, Q., Yang, J., Liu, J., Zhou, Q., Wang, X., Liu, M., Jiang, X., Yang, D., Jiang, H., Shen, J., Melcher, K., Chen, H., Jiang, Y., Cheng, X., Wang, M.W.*, Xie, X.*, Xu, H.E. *. Molecular recognition of morphine and fentanyl by the human μ-opioid receptor.Cell, 185(23), 4361-4375(2022).(Featured article; Best of Cell, 2023)
Zhuang, Y.#, Xu, P.#, Mao, C.#, Wang, L.#, Krumm, B.#, Zhou, X. E.#, Huang, S., Liu, H., Cheng, X., Huang, X. P., Shen, D. D., Xu, T., Liu, Y. F., Wang, Y., Guo, J., Jiang, Y., Jiang, H., Melcher, K., Roth, B. L.*, Zhang, Y.*, Zhang, C.*, Xu, H.E. *. Structural insights into the human D1 and D2 dopamine receptor signaling complexes. Cell. 184(4), 931-942(2021). (Cover Story)
Wang, Y.#,Zhuang, Y.#, *, DiBerto, J. F.#, Zhou, X. E., Schmitz, G. P., Yuan, Q., Jain, M. K., Liu, W., Melcher, K., Jiang, Y., Roth, B. L.*, Xu, H.E. *. Structures of the entire human opioid receptor family.Cell, 186(2), 413-427(2023). (ESI Highly Cited)
Xing, C.#,Zhuang, Y.#, Xu, T. H.#, Feng, Z.#, Zhou, X. E., Chen, M., Wang, L., Meng, X., Xue, Y., Wang, J., Liu, H., McGuire, T. F., Zhao, G., Melcher, K., Zhang, C.*, Xu, H.E.*, Xie, X. Q*. Cryo-EM structure of the human cannabinoid receptor CB2-Gi signaling complex.Cell, 180(4), 645-654(2020).
Wang, Y. #, Liu, W. #, Xu, Y., He, X., Yuan, Q., Luo, P., Fan, W., Zhu, J., Zhang, X., Cheng, X., Jiang, Y., Xu, H.E. *, Zhuang, Y. *. Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins. Nat Chem Biol, 19(11), 1351-1360 (2023).
Fan,W. #, Xu,Y. #, He, X. #, Luo, P., Zhu, J.,Li, J., Wang, R., Yuan, Q., Wu, K., Hu, W.,Zhao, Y., Xu, S., Cheng, X., Wang, Y.*,Xu, H.E. *,Zhuang, Y.*. Molecular basis for the activation of PAF receptor by PAF. Cell Rep, 43(7), 114422 (2024).
Wang, Y., Xu, Y., Wang, Y., Zhang, J., Chen, L., He, X., Fan, W., Wu, K., Hu, W., Cheng, X.,Yang, G., Xu, H.E. *,Zhuang, Y.*,Sun, S.*. Selective ligand recognition and activation of somatostatin receptors SSTR1 and SSTR3. PNAS, 121(41), p.e2400298121 (2024).
Fan, L.,Zhuang, Y. #, Wu, H., Li, H., Xu, Y., Wang, Y., He, L., Wang, Shishan, Chen, Z., Cheng, J. *,Xu, H.E. *, Wang, Sheng*. Structural basis of psychedelic LSD recognition at dopamine D1 receptor. Neuron, 112(19), 3295-3310 (2024).
Zhuang, Y.#, Krumm, B.#, Zhang, H.#, Zhou, X. E., Wang, Y., Huang, X. P., Liu, Y., Cheng, X., Jiang, Y., Jiang, H., Zhang, C., Yi, W., Roth, B. L.*, Zhang, Y.*, Xu, H.E. *. Mechanism of dopamine binding and allosteric modulation of the human D1 dopamine receptor. Cell Res, 31(5), 593-596 (2021).
Zhuang, Y.#, Wang, L.#, Guo, J., Sun, D., Wang, Y., Liu, W., Xu, H.E. *. and Zhang, C. *. Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2.Nat Commun, 13, 1054 (2022).
Zhuang, Y.#, Liu, H.#, Zhou, X. E., Kumar Verma, R., de Waal, P. W., Jang, W., Xu, T. H., Wang, L., Meng, X., Zhao, G., Kang, Y., Melcher, K., Fan, H., Lambert, N. A., Xu, H.E.*, Zhang, C. *. Structure of formylpeptide receptor 2-Gi complex reveals insights into ligand recognition and signaling. Nat Commun, 11, 885(2020).
Liu, Q#, Yang, D#,Zhuang, Y.#, Croll, T. I., Cai, X., Dai, A., He, X., Duan, J., Yin, W., Ye, C., Zhou, F., Wu, B., Zhao, Q., Xu, H.E.*, Wang, M.W.*, Jiang, Y*. Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor.Nat Chem Biol, 17(12), 1238-1244 (2021).
Xu, P. #, Huang, S. #, Krumm, B.E. #,Zhuang, Y. #, Mao, C. #, Zhang, Y., Wang, Y., Huang, X.P., Liu, Y.F., He, X., Li, H., Yin, W., Jiang, Y., Zhang, Y. *, Roth, B.L. *, Xu, H.E. *. Structural genomics of the human dopamine receptor system.Cell Res, 33, 604-616(2023).(Featured article)
Wang, Y.#, Guo, S.#,Zhuang, Y.#, Yun, Y.#, Xu, P.#, He, X., Guo, J., Yin, W., Xu, H. E. *, Xie, X.*, Jiang, Y*. Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor.Nat Commun, 12, 5064 (2021).
Luo, P., Xin, W., Guo, S., Li, X., Zhang, Q., Xu, Y.,He, X., Wang Y., Fang, W., Yuan, Q., Wu, K., Hu, W.,Zhuang, Y., Xu, H.E.,Xie, X. Structural insights into the agonist activity of the nonpeptide modulator JR14a on C3aR.Cell Discov, 11(1), 7 (2025).
Duan, J.#, Shen, D.D.#, Zhou, X.E.#, Bi, P.#, Liu, Q.F., Tan, Y.X.,Zhuang, Y., Zhang, H. B., Xu, P. Y., Huang, S. J., Ma, S. S., He, X. H., Melcher, K., Zhang, Y. *, Xu, H.E. *, Jiang, Y *. Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy.Nat Commun, 11, 4121 (2020).
Shi, Y., Ma, H.,Zhuang, Y., Wang, X. X., Jiang, Y., Xu, H.E. C10ORF12 modulates PRC2 histone methyltransferase activity and H3K27me3 levels. Acta Pharmacol Sin, 40, 1457–1465 (2019).
Dutka, P., Mukherjee, S., Gao, X., Kang, Y., de Waal, P.W., Wang, L.,Zhuang, Y., Melcher, K., Zhang, C., Xu, H.E., Kossiakoff, A. A. Development of “Plug and Play” Fiducial Marks for Structural Studies of GPCR Signaling Complexes by Single-Particle Cryo-EM. Structure, 27, 1-13 (2019).
Shi, Y, Wang, X, Zhuang, Y., Jiang, Y., Melcher, K., Xu, H.E. Structure of the PRC2 complex and application to drug discovery.Acta Pharmacol Sin, 38 (7), 963-976(2017).
