Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

Dr. Zhaobing Gao graduated with his Ph.D degree from Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, and received his postdoctoral training at the University of Johns Hopkins. Now he is a professor and principle investigator of SIMM, and he also serves as deputy director of the institute and the director of Center for Neurological and Psychiatric Research and Drug Discovery. Dr. Zhaobing Gao’s research mainly focuses on ion channels involved in the neuronal hyeperexcitiblity disorders such as epilepsy and neuropathic pain. He established a systematic drug development platform and a drug safety evaluation platform on ion channels, which have provided technical services and supports for domestic drug research and development. He identified and reported two type of novel ion channels, MLKL and Satp_Ck. He has made significant progress in the discovery of new modulation mechanisms and new modulators targeting pharmacologically important channels for epilepsy and pain. As the major inventors, two anti-epilepsy drug candidates targeting ion channels are undergoing clinical studies.

Education:

2006.10 - 2010.03 Postdoctoral Research Fellow in pharmacology in Johns Hopkins University

2003.09 - 2006 .06 Ph.D, Shanghai Institute of Materia Medica, Chinese Academy of Sciences

2000.09 - 2003 .06 M.S, Tongji Medical College of Huazhong University of Science and Technology

1992.09 - 1997 .06 B.S, Taishan Medical College

Work Experience:

2013.09-Present Professor, Shanghai Institute of Materia Medica

2010.04 - 2013 .08 Associate Professor, Shanghai Institute of Materia Medica

Research Directions

The main research interests are ion channel pharmacology and drug discovery and development. Ion channels are an important class of therapeutic drug targets. The group mainly focuses on ion channels involved in neuronal disorders, including identification of novel functions and new modulation mechanism of ion channels, discovery of novel ion channel modulators and subsequent drug development.

Grants & Research Projects

1.The National Science Fund of Distinguished Young Scholars, Pharmacology on Ion Channels, Project Leader, 2019.01-2023.12

2.The National Natural Science Foundation of China, Identification of KCNQ4 channel as a drug target for treatment of visceral pain, Project Leader, 2018.01-2021.12

3.The Joint NSFC-ISF Research Program, Targeting the voltage sensor of ion channels: novel tools to explore channel gating and cure hyperexcitability disorders, 2014.10-2017.09

4.973, Ministry of Science and Technology, (MOST), China, Discovery of novel modulators and novel functions of membrane proteins, Project Leader, 2013.01-2017.08

5.The Science and Technology Major Project on “Key New Drug Creation and Manufacturing Program”, drug candidate CF312 targeting KCNQ potassium channels, Project Leader, 2012.01-2015.12

6.The National Natural Science Foundation of China, Investigation of drug ability of KCNQ potassium channels and identification of novel modulators, Project Leader, 2010.01-2013.12

Achievements

1.A whole set of drug development platform and drug safety evaluation platform for ion channels, which own the capabilities including high throughput screening, molecular mechanism investigation and in vivo animal experiments, were established. The platforms have provided technical services and supports for drug research and development in more than 100 units across the country. Based on the platforms, a series of novel ion channel modulators have been discovered. As the major inventors, two anti-epilepsy drug candidates targeting ion channels entered clinical studies.

2.Significant progress has been made in the discovery of new modulation mechanisms and new modulators targeting potassium and sodium channels for epilepsy. The critical roles of intracellular second messenger and membrane phospholipids in the plasticity of drug subtype selectivity and the dynamic interaction mechanism between the channels and the membrane phospholipids were revealed. The research showed that the gating charge pathway of potassium channels (KCNQ) was a new therapeutic drug target for epilepsy, and the activation of peripheral KCNQ channels alone could effectively relieve intense gout pain and neuropathic pain.

3.Two novel ion channels were identified and reported for the first time. The first one is the magnesium-permeable channel MLKL and the second one is the acetate channel Satp_Ck, which could be used as potential new drug targets for human diseases in the future.

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Social Titles

1.Chinese Society of Pharmacology, Council member

2.Shanghai Pharmacological Society, Council member

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Awards & Honors

2019.12 National candidate for the New Century Talents Project

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Pubilcations

Full Publication List

Selected Publications

1.Zhang, X.C., Yin, X.Z., Zhang, J.J., Li, A.N., Gong, H., Luo, Q.M., Zhang, H.Y. *, Gao, Z.B.*, Jiang, H.L.*, 2019. High-resolution mapping of brain vasculature and itsimpairment in the hippocampus of Alzheimer’s disease mice. National Science Review. doi: 10.1093/nsr/nwz124.

2.Qiu, B., Xia, B.Q., Zhou, Q.T., Lu, Y., He, M.M., Hasegawa, K., Ma, Z.B., Zhang, F.Y., Gu, L.C., Mao, Q.L., Wang, F., Zhao, S.W., Gao, Z.B.*, Liao, J.*, 2018. Succinate-acetate permease from Citrobacter koseri is an anion channel that unidirectionally translocates acetate. Cell Research. 28:644–654.

3.Ding, Q., Fang, S., Chen, X.Q., Wang, Y.X., Li, J., Tian, F.Y., Xu, X., Attali, B., Xie, X., Gao, Z.B.*, 2017.TRPA1 channel mediates organophosphate-induced delayed neuropathy. Cell Discov. doi: 10.1038/celldisc.2017.24.

4.Xia, B.Q., Fang S., Chen, X.Q., Hu, H.，Chen, P.Y., Wang, H.Y.*，Gao, Z.B.*, 2016. MLKL forms cation channels. Cell Research. 26: 1-12.

5.Lan, X., Fan, C.Y., Ji, W., Tian, F.Y., Xu, T.*, Gao, Z.B.*, 2016. Grafting voltage and pharmacological sensitivity in potassium channels. Cell Res. doi: 10.1038/cr.2016.57

6.Zheng, Y.M., Xu, H.Y., Zhan, L., Zhou, X.D., Chen, X.Q., Gao, Z.B.*, 2015. Activation of peripheral KCNQ channels relieves gout pain. Pain. 156(6):1025-1035.

7.Zhou, P.Z., Zhang, Y.M., Xu, H.Y., Chen, F., Chen, X.Q., Li, X., Pi, X.P., Nan, F.J.*, Gao, Z.B.*，2015. P-Retigabine: a N-propargyled Retigabine with Improved Brain Distribution and Enhanced Antiepileptic Activity. Mol Pharmacol. 87(1): 31-38.

8.Zhang, Q.S., Zhou, P.Z., Chen, Z.X., Li, M., Jiang, H.L., Gao, Z.B.*, Yang, H.Y.*, 2013. Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating. Proc Natl Acad Sci U S A. 110(50): 20093-20098.

9.Li, P., Chen, Z.X., Xu, H.Y., Sun, H.F., Li, H., Liu, H., Yang, H.Y.*, Gao, Z.B.*, Jiang, H.L.*, Li, M., 2013. The gating charge pathway of an epilepsy-associated potassium channel accommodates chemical ligands. Cell Research. 23 (9): 1106-1118.

10.Zhou, P.Z., Yu, H.B., Gu, M., Nan, F.J., Gao, Z.B.*, Li, M.*, 2013. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels. Proc Natl Acad Sci U S A. 110(21): 8726-8731.

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