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姓名:
高召兵
性别:
职称:
副院长
学历:
博士
电话:
 
传真:
 
电子邮件:
zbgao@simm.ac.cn
个人主页:
 
通信地址:
烟台市高新区滨海东路198号

 

 

 

 

 

 

 

 

  个人简介

 

高召兵,博士,研究员,博士生导师。1997年毕业于泰山医学院临床医学专业,2003年于同济医学院神经生物学系毕业并获得硕士学位,同年考入中科院上海药物所,开展天然产物对离子通道调制的研究工作,2006年获得神经药理学博士学位,旋即赴美国约翰霍普金斯大学神经科学系从事博士后研究工作,主要开展离子通道新型调制剂的发现和分子调控机制研究。2010年回国工作以来,主要开展与神经系统疾病相关的离子通道药理学研究和药物发现。

 

  工作经历

 

2013.09 至今

中科院上海药物所,研究员

2010.04-2013.08

中科院上海药物所,副研究员

2006.10-2010.03

美国约翰霍普金斯大学神经科学系/离子通道中心,博士后

 

  研究方向

 

离子通道药理学:围绕与神经系统重大疾病有关的离子通道为中心,建立离子通道药物研发平台,推进离子通道新机制、新功能研究,发现新型离子通道,发展新型调制剂,开发靶向离子通道的抗癫痫新药。

 

  科研项目

 

承担包括973、国家重大新药创制候选新药、自然基金中外合作、自然基金面上项目等多项科研项目。

 

  科研成果

 

1.建立了系统完备的离子通道药物发现平台,开展心脏安全性评价工作,发现系列新型离子通道小分子调节剂,作为主要发明人的两个靶向离子通道的新药进入临床研究。

2.靶向KCNQ通道癫痫药物的新机制和新药发现取得显著进展:证明抗癫痫药物的亚型选择性与细胞膜磷脂的水平密切相关,并揭示膜磷脂调控离子通道的分子机制;确定通道电压门控电荷通路是抗癫痫药物的新位点;通过移植通道电压感受区,实现小分子敏感性在钾通道中的移植;一个抗癫痫候选药物正在进行系统性临床前研究。

3.新型离子通道发现:证明程序性坏死蛋白MLKL形成通透镁离子的新型离子通道,这是我国学者发现的首个人源离子通道;发现并确证首个乙酸通道,打破了认为乙酸由转运体运输的传统学说。

 

  代表论著

 

1. Xiaochuan Zhang, Xianzhen Yin, Jingjing Zhang, Anan Li, Hui Gong, Qingming Luo, Haiyan Zhang, Zhaobing Gao*. Hualiang Jiang*,High-resolution mapping of brain vasculature and its impairment in the hippocampus of Alzheimer's disease mice.National Science Review, Volume 6, Issue 6, November 2019, Pages 1223–1238, https://doi.org/10.1093/nsr/nwz124.

    2. Li YF, Zheng YM, Yu Y, Gan Y, Gao ZB*. Inhibitory effects of lappaconitine on the neuronal isoforms of voltage-gated sodium channels. Acta Pharmacol Sin. 2018 Jul 10. doi: 10.1038/s41401-018-0067-x. Epub 2018 Jul 10.

    3. Qiu B, Xia B, Zhou Q, Lu Y, He M, Hasegawa K, Ma Z, Zhang F, Gu L, Mao Q, Wang F, Zhao S, Gao Z*, Liao J*. Succinate-acetate permease from Citrobacter koseri is an anion channel that unidirectionally translocates acetate. Cell Res. 2018 Jun;28(6):644-654. doi:10.1038/s41422-018-0032-8. Epub 2018 Mar 27.

    4. Bai F, Pi X, Li P, Zhou P, Yang H, Wang X, Li M, Gao Z*, Jiang H*..A Statistical Thermodynamic Model for Ligands Interacting With Ion Channels: Theoretical Model and Experimental Validation of the KCNQ2 Channel. Front Pharmacol. 2018 Mar 9;9:150. doi: 10.3389/fphar.2018.00150. eCollection 2018.

    5. Luo Y, Wang A, Liu M, Lei T, Zhang X, Gao Z, Jiang H, Gong H, Yuan J.Label-free brainwide visualization of senile plaque using cryo-micro-optical sectioning tomography.Opt Lett. 2017 Nov 1;42(21):4247-4250. doi: 10.1364/OL.42.004247.

    6. Zheng YM, Wang WF, Li YF, Yu Y*, Gao ZB*. Enhancing inactivation rather than reducing activation of Nav1.7 channels by a clinically effective analgesic CNV1014802.Acta Pharmacol Sin. 2017 Nov 2. doi: 10.1038/aps.2017.151.

    7. Ding Q, Fang S, Chen X, Wang Y, Li J, Tian F, Xu X, Attali B, Xie X, Gao Z*. TRPA1 channel mediates organophosphate-induced delayed neuropathy. Cell Discov. 2017 Aug 1;3:17024. doi: 10.1038/celldisc.2017.24. eCollection 2017.

    8. Xi Lan, Chunyan Fan#, Wei Ji, Fuyun Tian, Tao Xu*, Zhaobing Gao*. Grafting voltage and pharmacological sensitivity in potassium channels. Cell research, 2016 Aug;26(8):935-45.

    9. Bingqing Xia, Sui Fang, Xueqin Chen, Hong Hu, Peiyuan Chen, Huayi Wang*,Zhaobing Gao*. MLKL forms cation channels. Cell research, 2016 May;26(5):517-28.

    10. Attali B#*, Gao ZB#*. Ion channels research in the post-genomic era. Acta Pharmacol Sin. 2016 Jan;37(1):1-3. doi: 10.1038/aps.2015.144. No abstract available.

    11. Li JL, Gao ZB*, Zhao WM*.Identification and Evaluation of Antiepileptic Activity of C21 Steroidal Glycosides from the Roots of Cynanchum wilfordii. J Nat Prod. 2016 Jan 22;79(1):89-97. doi: 10.1021/acs.jnatprod.5b00766. Epub 2015 Dec 30.

    12. Yue JF, Qiao GH, Liu N, Nan FJ*, Gao ZB*. Novel KCNQ2 channel activators discovered using fluorescence-based and automated patch-clamp-based high-throughput screening techniques. Acta Pharmacol Sin. 2016 Jan;37(1):105-10. doi: 10.1038/aps.2015.142.

    13. Zheng Y, Xu H, Zhan L, Zhou X, Chen X, Gao Z*. Activation of peripheral KCNQ channels relieves gout pain. Pain. 2015 Jun;156(6):1025-35. doi: 10.1097/j.pain.0000000000000122.

    14. P Zhou, Y Zhang, H Xu, F Chen, X Chen, X Li, X Pi, L Wang, L Zhan, F Nan*,Zhaobing Gao*. P-Retigabine: a N-propargyled Retigabine with Improved Brain Distribution and Enhanced Antiepileptic Activity. Mol Pharmacol. 2015 January 87:31–38

    15. Fu J, Gao Z, Shen B, Zhu MX*.Canonical transient receptor potential 4 and its small molecule modulators.Sci China Life Sci. 2015 Jan;58(1):39-47. doi: 10.1007/s11427-014-4772-5. Epub 2014 Dec 5.

    16. Ji X, Xia C, Wang J, Su M, Zhang L, Dong T, Li Z, Wan X, Li J, Li J*, Zhao L, Gao Z, Jiang H*, Liu H*.Design, synthesis and biological evaluation of 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors, Eur J Med Chem. 2014 Oct 30;86:242-56.

    17. P Li, X Chen, Q Zhang, Y Zheng, H Jiang, H Yang*, Zhaobing Gao*. The Human Ether-A-Go-Go-Related Gene Activator NS1643 Enhances Epilepsy-Associated KCNQ Channels. J Pharmacol Exp Ther. 2014;351(3):596-604.

    18. Xia Wan, Yungang Lu, Xueqin Chen, Jian Xiong, Yuanda Zhou, Ping Li, Min Li, Michael X.Zhu*, Zhaobing Gao*, Bimodal voltage dependence of TRPA1: mutations of a key pore helix residue reveal strong intrinsic voltage-dependent inactivation. Pflugers Arch. 2014;466(7):1273-87.

    19. Hu HN, Zhou PZ, Chen F, Li M, Nan FJ*, Gao ZB*, Discovery of a retigabine derivative that inhibits KCNQ2 potassium channels, Acta Pharmacol Sin. 2013 Oct;34(10):1359-66.

    20. Pingzheng Zhou, Haibo Yu, Min Gu, Fa-jun Nan, Zhaobing Gao*, Min Li*,PIP2 alters pharmacological selectivity for epilepsy-causing KCNQ channels ,PNAS, 2013 ;110(21):8726-31.

    21. Qiansen Zhang, Pingzheng Zhou, Zhuxi Chen, Min Li, Hualiang Jiang, Zhaobing Gao*, Huaiyu Yang*, Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating. PNAS 2013;110(50):20093-8.

    22. Ping Li, Zhuxi Chen, Haiyan Xu, Haifeng Sun, Hao Li, Hong Liu, Huaiyu Yang*,Zhaobing Gao*, Hualiang Jiang*, and Min Li, The gating charge pathway of an epilepsy-associated potassium channel accommodates chemical ligands, Cell Research, 2013; 23(9):1106-18.

    23. Yao XG, Chen F, Li P, Quan L, Chen J*, Yu L, Ding H, Li C, Chen L, Gao Z, Wan P, Hu L*, Jiang H, Shen X*, Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models, J Ethnopharmacol. 2013 Oct 28;150(1):285-97.

    24. Ping Li, Jin Zhu, Qingya Kong, Baifeng Jiang, Xia Wan, Jinfeng Yue, Min Li, Hualiang Jiang,Jian Li* and Zhaobing Gao*, The ethylene bis-dithiocarbamate fungicide Mancozeb activates voltage-gated KCNQ2 potassium channel. Toxicology Letters, 2013;219 (3):211-7.

    25. Yueming Zheng, Xuejing Zhu,Pingzheng Zhou, Xi Lan, Haiyan Xu, Min Li*,Zhaobing Gao*, Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants. PLoS One. 2012;7(12):e51820. doi: 10.1371/journal.pone.0051820.

    26. Yuanxiang Wang,Jing Ai,Jinfeng Yue,Xia Peng,bYinchun Ji,Ailing Zhao,Xin,Gao,Ying Wang,Yi Chen,Gang Liu, Zhaobing Gao*, Meiyu Geng* and Ao Zhang*,Further SAR studies on 3,5-diamino-7-trifluoromethylquinolines as highly potent tyrosine kinase c-Met inhibitors:efforts to correct hERG inhibition, Med. Chem. Commun., 2012;1423(3):1423-1427.

    27. Liu HB, Zhang H, Li P, Gao ZB, Yue JM*,Chukrasones A and B: potential Kv1.2 potassium channel blockers with new skeletons from Chukrasia tabularis, Org Lett. 2012 Sep 7;14(17):4438.

    28. Li P, Sun HF, Zhou PZ, Ma CY, Hu GY, Jiang HL, Li M, Liu H*, Gao ZB*,Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG channel and three neuronal potassium channels, Acta Pharmacol Sin. 2012 Jun;33(6):728-36.

    29. Du XN, Zhang X, Qi JL, An HL, Li JW, Wan YM, Fu Y, Gao HX, Gao ZB*, Zhan Y, Zhang HL*,Characteristics and molecular basis of celecoxib modulation on K(v)7 potassium channels, Br J Pharmacol. 2011 Nov;164(6):1722-37.

    30. Zhou PZ, Babcock J, Liu LQ, Li M*, Gao ZB*,.Activation of human ether-a-go-go related gene (hERG) potassium channels by small molecules, Acta Pharmacol Sin. 2011 Jun;32(6):781-8.

 

  社会任职

 

中国药理学会 理事

上海市药学会药理专委会副主任委员

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