Home CAS Center for Excellence
  
  
  

Faculty

Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
 
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
 
Principal Investigators
 
Wang Sheng
Ph.D., Professor
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese
Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China
Email: wangsheng@sibcb.ac.cn

Research Areas
Functional and Structural Pharmacology of Membrane Protein

Research Interests

We combine structural biology and chemical biology to better understand how dopamine and serotonin mediated signaling that controls reward, pleasure, mood, cognition and consciousness.

Our laboratory has two major research focuses:
 
1.    Structural pharmacology of dopamine and serotonin receptors
Dopamine and serotonin receptors are implicated in many neurological processes, including mood, pleasure, cognition, memory and learning. Thus, dopamine and serotonin receptors are common neurologic drug targets; such as, antipsychotics are often dopamine and serotonin receptors antagonists. Previously, we identified unexpectedly deep penetration of antipsychotic into D2 dopamine receptor, D4 dopamine receptor selective binding pocket and hallucinogen LSD¨s psychoactive potency. We aim to continue to understand how serotonin and dopamine receptors recognize extracellular cues and translate this chemical information into distinct conformations responsible for signaling.

2.    Structure Based Drug Design
In collaboration with computational and medicinal chemistry groups, we are trying to leverage mechanistic insights from our structural and molecular studies to generate novel tool compounds targeting dopamine or serotonin receptor. As part of a highly collaborative effort, we previously identified a selective D4 dopamine receptor partial agonist using computational docking and structure-guided optimization. We aim to continue to leverage our structural and biophysical insights to identify novel probes large computational screening campaigns, that are then rapidly improved and customized towards desired pharmacology using medicinal chemistry. We anticipate that these probes will both serve as tools to interrogate signaling and as therapeutic leads in themselves.

Selected Publications

  1. S . Wang$, T. Che, A. Levit, B. K. Shoichet, D. Wacker$, B. L. Roth.$, Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone. Nature, (doi:10.1038/nature25758) ($corresponding author).
  2. S. Wang*,$, D. Wacker*,$, A. Levit*, T. Che, R. Betz, J. D. McCorvy, A. J. Venkatakrishnan, X.P. Huang, R. Dror, B. K. Shoichet$, B. L. Roth$, High Resolution Structures of the D4 Dopamine Receptor Template the Discovery of Novel Specific Agonists. Science, 358, 381-386 (2017) ($corresponding author, * co-first author).
  3. D. Wacker*, S. Wang*, J. D. McCorvy*, R. Betz, A. J. Venkatakrishnan, A. Levit, Z. Schools, D. E. Nichols, B. K. Shoichet, R. Dror, B. L. Roth, Crystal structure of an LSD bound human serotonin receptor. Cell, 168, 377-389 (2017) (Cover Story) (*co-first author).
  4. S. Wang*, J. Yin*, D. Chen, F. Nie, X. Song, C. Fei, H. Miao, C. Jing, W. Ma, L. Wang, S. Xie, C. Li, R. Zeng, W. Pan, X. Hao, L. Li, Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction. Nature Chem. Biol., 9, 579-585 (2013) (*co-first author).
  5. T. Che, S. Majumdar, S. A. Zaidi, C. Kormos, J. D. McCorvy, S. Wang, R. Uprety, E. Vardy, B. E. Krumm, G. W. Han, M. Lee, E. Pardon, J. Steyaert, X. Huang, G. W. Pasternak, I. F.Carroll, R. C. Stevens, V. Cherezov, V. Katritch, D. Wacker1, Bryan L. Roth, Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor. Cell, 172, 55-67 (2018).
  6. X. P. Huang, J. Karpiak, W. K. Kroeze, H. Zhu, X. Chen, S. S. Moy, K. A. Saddoris, V. D. Nikolova, M. S. Farrell, S. Wang, T. J. Mangano, D. A. Deshpande, A. Jiang, R. B. Penn, J. Jin, B. H. Koller, T. Kenakin, B. K. Shoichet, B. L. Roth, Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65. Nature, 527, 477-483 (2015).
  7. X. Song, S. Wang, L. Li, New insights into the regulation of Axin function in canonical Wnt signaling pathway. Protein & cell, 5, 186-193 (2014).
  8. J. Shen, X. Sheng, Z. Chang, Q. Wu, S. Wang, Z. Xuan, D. Li, Y. Wu, Y. Shang, X. Kong, L. Yu, L. Li, K. Ruan, H. Hu, Y. Huang, L. Hui, D. Xie, F. Wang, R. Hu, Iron metabolism regulates p53 signaling through direct heme-p53 interaction and modulation of p53 localization, stability, and function. Cell reports, 7, 180-193 (2014).
  9. Z. Li, F. Nie, S. Wang, L. Li, Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation. Proc. Natl. Acad. Sci. USA, 108, 3116-3123 (2011).
  10. W. Wang, H. Liu, S. Wang, X. Hao, L. Li, A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/beta- catenin signaling and colon cancer cell tumorigenesis. Cell research, 21, 730-740 (2011).

Education Background & Academic Experience

2018-present: Principle investigator, Shanghai Institute of Biochemistry and Cell Biology, SIBS, CAS
2013-2018: Postdoctoral researcher, National Institute of Mental Health, Psychoactive Drug Screening Program, US
2013-2018: Postdoctoral researcher, University of North Carolina at Chapel Hill, Department of Pharmacology, US
2007-2013: Graduate student (PhD), Shanghai Institute of Biochemistry and Cell Biology, CAS
2004-2007: undergraduate student, College of Life Sciences, Wuhan University
2003-2007: undergraduate student, College of Food Science & Technology, Huazhong Agricultural University

 

Copyright © 2017-2020 Shanghai Institute of Biochemistry and Cell Biology, CAS. All rights reserved