Principal Investigator
Center for Neurological and Psychiatric Research and Drug Discovery (CNPRDD);Ion Channel Research Platform
Personal Homepage
CONTACT
liyang@simm.ac.cn
+86-021-50803107
201203
555 Zuchongzhi Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai, P.R.China
Dr. Yang Li was graduated with his PhD degree from SIMM and received his postdoctoral training at University of Texas Health Science Center (San Antonio) and UT Southwestern Medical Center at Dallas, where he served also as Assistant Investigator for 1 year. From September 2009, he was recruited to SIMM as PI. His research interests include new targets, new drugs, and pharmacological mechanisms for mental illness, such as, depression, anxiety disorder, and Parkinson's disease. Build up screening service for targets as monoamine receptors (DA, 5-HT,NE), ion channels (hERG, KCNQ, K2P, CFTR). Dr. Li has published more than 40 papers in academic journals such as Cell, Nature Communications and PNAS. He serves as the Deputy Secretary-General of the Chinese Neuropsychiatric Pharmacology Society, Associate editor of Frontiers in Physiology.
Education:
1988.09 - 1992.06 Shandong University, Department of Biology, undergraduate
1996.09 - 1999.06 East China Normal University, Masters
1999.09 - 2002.06 Shanghai Institute of Materia Medica, Ph.D.
Work Experience:
2009.09-Present Professor, SIMM
1.Structure and function of ion channels.
2.Pharmacological mechanisms of mental illness and new drug discovery.
Structure, function and pharmacology of ion channels. By combining the crystal structure and single channel electrophysiological methods, we clarify the competitive permeability and conductance mechanism of MthK potassium channel; discover new drug targets of MthK potassium channel; explore the anion-selective mechanism of mechano-sensitive channel; elucidate the regulation mechanism of KCNQ potassium channels by PIP2; characterize the novel calcium channel at the endoplasmic reticulum.
Pharmacology of neuropsychiatric diseases. We established the receptor binding assay and behavioral tests to screen for compounds designed for the treatment of anti-depression, anxiety, schizophrenia diseases. We carried out mechanism research of interaction between dopamine receptors and ion channels. Probed by the compounds from Chinese medicine, fumarate (THP), L-stepholidine (l-SPD), timosaponin and its structural derivatives, we conducted preliminary exploration on the neural pathways and cellular mechanisms relating to mental illness, such as depression, anxiety, and schizophrenia.
Full Publication List
Selected Publications
1.Zhang S, Liu Y, Zhang B, et al. Molecular insights into the human CLC-7/Ostm1 transporter. Science Advances. 2020;6(33):eabb4747. Published 2020 Aug 12. doi:10.1126/sciadv.abb4747
2.X. Xu, X. Xu, Y. Hao, X. Zhu, J. Lu, X. Ouyang, Y. Lu, X. Huang, Y. Li, J. Wang, X. Shen, Antispasmodic Drug Drofenine as an Inhibitor of Kv2.1 Channel Ameliorates Peripheral Neuropathy in Diabetic Mice, iScience 23(10) (2020) 101617.
3. Y. Ma, Q. Luo, J. Fu, Y. Che, F. Guo, L. Mei, Q. Zhang, Y. Li, H. Yang, Discovery of an Inhibitor for the TREK-1 Channel Targeting an Intermediate Transition State of Channel Gating, J Med Chem 63(19) (2020) 10972-10983.
4.Chai H, Cheng X, Zhou B, Zhao L, Lin X, Huang D, et al. Structure-Based Discovery of a Subtype-Selective Inhibitor Targeting a Transient Receptor Potential Vanilloid Channel. Journal of Medicinal Chemistry. 2019;62(3):1373-84.
5.Gao, S., D. Wang, H. Chai, J. Xu, T. Li, Y. Niu, X. Chen, F. Qiu, Y. Li, H. Li and L. Chen (2019). "Unusual ent-Labdane Diterpenoid Dimers and their Selective Activation of TRPV Channels." J Org Chem 84(21): 13595-13603.
6.Li, Q., B. Zhang, H. Cao, W. Liu, F. Guo, F. Shen, B. Ye, H. Liu, Y. Li and Z. Liu (2020). "Oxytocin Exerts Antidepressant-like effect by potentiating dopaminergic synaptic transmission in the mPFC." Neuropharmacology 162: 107836.
7.Shen FY, Song YC, Guo F, Xu ZD, Li Q, Zhang B, et al. Cognitive Impairment and Endoplasmic Reticulum Stress Induced by Repeated Short-Term Sevoflurane Exposure in Early Life of Rats. Front Psychiatry. 2018;9:332.
8.Y. Song, B. Zhang, F. Guo, M. Yang, Y. Li, Z.Q. Liu, Identification of Intracellular beta-Barrel Residues Involved in Ion Selectivity in the Mechanosensitive Channel of Thermoanaerobacter tengcongensis. Frontiers in physiology 8 (2017) 832.
9.J. Yu, B. Zhang, Y. Zhang, C.Q. Xu, W. Zhuo, J. Ge, J. Li, N. Gao, Y. Li, M. Yang, A binding-block ion selective mechanism revealed by a Na/K selective channel. Protein & cell. 2017. Sep 18. doi: 10.1007/s13238-017-0465-8.
10.Q. Luo, L. Chen, X. Cheng, Y. Ma, X. Li, B. Zhang, L. Li, S. Zhang, F. Guo, Y. Li, H. Yang, An allosteric ligand-binding site in the extracellular cap of K2P channels, Nature Communications 8(1) (2017) 378.
11.B. Zhang, F. Guo, Y. Ma, Y. Song, R. Lin, F.-Y. Shen, G.-Z. Jin, Y. Li, Z.-Q. Liu, Activation of D1R/PKA/mTOR signaling cascade in medial prefrontal cortex underlying the antidepressant effects of l-SPD, Scientific Reports 7(1) (2017) 3809.
12.Wang QC, Zheng Q, Tan H, Zhang B, Li X, Yang Y, et al. TMCO1 Is an ER Ca(2+) Load-Activated Ca(2+) Channel. Cell 2016;165:1454-66.
13.Zhou TT, Quan LL, Chen LP, Du T, Sun KX, Zhang JC, et al. SP6616 as a new Kv2.1 channel inhibitor efficiently promotes beta-cell survival involving both PKC/Erk1/2 and CaM/PI3K/Akt signaling pathways. Cell death & disease 2016;7:e2216.
14.Guo F, Zhang B, Fu Z, Ma Y, Gao Y, Shen F, et al. The rapid antidepressant and anxiolytic-like effects of YY-21 involve enhancement of excitatory synaptic transmission via activation of mTOR signaling in the mPFC. European neuropsychopharmacology 2016;26:1087-98.
15.Zhang Q, Guo F, Fu ZW, Zhang B, Huang CG, Li Y. Timosaponin derivative YY-23 acts as a n8on-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice. Acta pharmacologica Sinica 2016;37:166-76.
16.Wang JJ, Li Y. KCNQ potassium channels in sensory system and neural circuits. Acta pharmacologica Sinica 2016;37:25-33.
17.Chen L, Zhang Q, Qiu Y, Li Z, Chen Z, Jiang H, et al. Migration of PIP2 lipids on voltage-gated potassium channel surface influences channel deactivation. Scientific reports 2015;5:15079. (IF = 5.2)
18.Ye D, Li Y, Zhang X, Guo F, Geng L, Zhang Q, et al. TREK1 channel blockade induces an antidepressant-like response synergizing with 5-HT1A receptor signaling. European neuropsychopharmacology 2015;25:2426-36. (IF = 4.5)
19. Guo F, Zhang Q, Zhang B, Fu Z, Wu B, Huang C,. Li Y. Burst-firing patterns in the prefrontal cortex underlying the neuronal mechanisms of depression probed by antidepressants. The European journal of neuroscience 2014; 40 (10): 3538-47. (IF=3.9)
20.Geng LY, Ye DQ, Shi YY, Xu Z, Pu MJ, Li ZY, et al. Influence of genetic polymorphisms involved in the hypothalamic-pituitary-adrenal axis and their interactions with environmental factors on antidepressant response. CNS neuroscience & therapeutics. 2014;20(3):237-43.
21. Zhang X, Wang J, Feng Y, Ge J, Li W, Sun W, et al. Structure and molecular mechanism of an anion-selective mechanosensitive channel of small conductance. PNAS 2012;109:18180-5. (IF = 9.5)
22. Derebe MG, Zeng W, Li Y, Alam A, Jiang Y. Structural studies of ion permeation and Ca2+ blockage of a bacterial channel mimicking the cyclic nucleotide-gated channel pore. PNAS. 2011; 108(2):592-7. (IF = 9.5)
23. Sheng Ye, Yang Li & Youxing Jiang. Novel insights into K+ selectivity from high-resolution structures of an open K+ channel pore. Nature structural & molecular biology 2010, Vol.17, 1019-1023 (IF = 13.3)
24.Ning Shi, Weizong Zeng, Sheng Ye, Yang Li* and Youxing Jiang*. Crucial Points within the Pore as Determinants of K+ Channel Conductance and Gating. JOURNAL OF MOLECULAR BIOLOGY, 411(1), pp 27-35, 2011/8/5. (IF = 4.5)
25.Derebe MG, Zeng W, Li Y, Alam A, Jiang Y. Structural studies of ion permeation and Ca2+ blockage of a bacterial channel mimicking the cyclic nucleotide-gated channel pore. PANS. 2011 Jan 11;108(2):592-7.
26.Li Y, Berke I, Chen L, Jiang Y. Gating and inward rectifying properties of the MthK K+ channel with and without the gaing ring. J. Gen. Physiol. 2007 Feb;129(2):109-20.
27.Ye S, Li Y, Chen L, Jiang Y. Crystal Structures of a Ligand-free MthK Gating Ring: Insights into the Ligand Gating Mechanism of K+ Channels. Cell. 2006 Sep 21; 126(6): 1161-1173
28.Gamper N, Zaika O, Li Y, Martin P, Hernandez CC, Perez MR, Wang AY, Jaffe DB, Shapiro MS. Oxidative modification of M-type K(+) channels as a mechanism of cytoprotective neuronal silencing. EMBO J. 2006 Oct 18;25(20):4996-5004.
29.Li Y, Gamper N, Hilgemann DW, Shapiro MS. Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate.J. Neurosci. 2005 Oct 26;25(43):9825-35.
30.Gamper N, Li Y, Shapiro MS. Structural requirements for differential sensitivity of KCNQ K+ channels to modulation by Ca2+/calmodulin. Mol Biol Cell. 2005 Aug;16(8):3538-51.
31. Li Y, Langlais P, Gamper N, Liu F, Shapiro MS. Dual phosphorylations underlie modulation of unitary KCNQ K+ channels by Src tyrosine kinase. J. Biol. Chem. 2004 Oct 29;279(44):45399-407.
32.Li Y, Gamper N, Shapiro MS. Single-channel analysis of KCNQ K+ channels reveals the mechanism of augmentation by a cysteine-modifying reagent. J. Neurosci. 2004 Jun 2;24(22):5079-90.
33.Liu, H.; Li, Y.; Song, M.; Tan, X.; Cheng, F.; Zheng, S.; Shen, J.; Luo, X.; Ji, R.; Yue, J.; Hu, G.; Jiang, H.; Chen, K. Structure-based discovery of potassium channel blockers from natural products: virtual screening and electrophysiological assay testing. Chem. Biol. 2003, 10, 1103-1113.
34. Liu H, Gao ZB, Yao Z, Zheng S, Li Y, Zhu W, Tan X, Luo X, Shen J, Chen K, Hu GY, Jiang H. Discovering potassium channel blockers from synthetic compound database by using structure-based virtual screening in conjunction with electrophysiological assay. J. Med .Chem. 2007 Jan 11;50(1):83-93.
35. Yang Li, Guo-Yuan Hu. Huperzine A, a nootropic agent, inhibits fast transient potassium current in rat dissociated hippocampal neurons. Neuroscience Letters 324(20 02) 25–28
36. Yang Li, Guo-Yuan Hu Huperzine A inhibits the sustained potassium current in rat dissociated hippocampal neurons. Neuroscience Letters 329 (2002) 153–156
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