高召兵,博士,研究員,博士生導師。
現任中國科學院上海藥物研究所副所長、課題組長、神經藥理學研究國際科學家工作站執行主任。
基本介紹
- 中文名:高召兵
- 國籍:中國
- 畢業院校:泰山醫學院(學士)、同濟醫學院(碩士)、中國科學院上海藥物研究所(博士)
- 現任職務:中國科學院上海藥物研究所副所長
人物經歷,教育經歷,工作經歷,學術任職,職務任免,研究方向,主要成就,專利成果,所獲榮譽,科研活動,科研項目,參與會議,代表論文,
人物經歷
教育經歷
1997年畢業於泰山醫學院臨床醫學專業,2003年於同濟醫學院神經生物學系畢業並獲得碩士學位,同年考入中科院上海藥物所,開展天然產物對離子通道調製的研究工作,2006年獲得神經藥理學博士學位,旋即赴美國約翰霍普金斯大學神經科學系從事博士後研究工作,主要開展離子通道新型調製劑的發現和分子調控機制研究。
工作經歷
2010-04~2013-10, 中科院上海藥物所, 副研究員
2013-10~2020-08, 中科院上海藥物研究所, 研究員
2020-08~, 中科院上海藥物研究所, 副所長
學術任職
中國藥理學會 理事
上海市藥學會藥理專委會副主任委員
職務任免
2022年10月28日,免去高召兵同志上海藥物研究所副所長職務。
研究方向
離子通道藥理學:圍繞與神經系統重大疾病有關的離子通道為中心,建立離子通道藥物研發平台,推進離子通道新機制、新功能研究,發現新型離子通道,發展新型調製劑,開發靶向離子通道的抗癲癇新藥。
主要成就
1.建立了系統完備的離子通道藥物發現平台,開展心臟安全性評價工作,發現系列新型離子通道小分子調節劑,作為主要發明人的兩個靶向離子通道的新藥進入臨床研究。
2.靶向KCNQ通道癲癇藥物的新機制和新藥發現取得顯著進展:證明抗癲癇藥物的亞型選擇性與細胞膜磷脂的水平密切相關,並揭示膜磷脂調控離子通道的分子機制;確定通道電壓門控電荷通路是抗癲癇藥物的新位點;通過移植通道電壓感受區,實現小分子敏感性在鉀通道中的移植;一個抗癲癇候選藥物正在進行系統性臨床前研究。
3.新型離子通道發現:證明程式性壞死蛋白MLKL形成通透鎂離子的新型離子通道,這是我國學者發現的首個人源離子通道;發現並確證首個乙酸通道,打破了認為乙酸由轉運體運輸的傳統學說。
專利成果
( 1 ) 苯溴馬隆在製備電壓門控鉀離子通道KCNQ激動劑中的套用, 2015, 第 1 作者, 專利號: 2015100336398.9
( 2 ) 一類新穎的KCNQ鉀通道激動劑的製備方法和用途 , 2014, 第 3 作者, 專利號: 201410175315.X
( 3 ) 六氯酚作為新型電壓門控鉀離子通道激動劑 , 2012, 第 2 作者, 專利號: 201210283106.8
( 4 ) N,N-二取代哌嗪類衍生物及其製備方法、藥物組合物和用途, 2010, 第 5 作者, 專利號: 200610023677.2
所獲榮譽
美國心臟學會博士後Fellowship,2007
2018年8月3日,根據《國家傑出青年科學基金項目管理辦法》的有關規定,國家自然科學基金委員會將2018年度國家傑出青年科學基金建議資助項目申請人名單予以公布,高召兵在名單之中。
科研活動
科研項目
( 1 ) KCNQ鉀離子通道成藥性功能確證及其新型激動劑設計, 負責人, 國家任務, 2010-01--2013-12
( 2 ) 利用納米操作機器人研究膜脂構成對細胞機械特性及鉀通道反應性的影響, 負責人, 研究所自選, 2011-01--2011-12
( 3 ) KCNQ鉀離子通道作為治療難治性癲癇靶點的驗證及候選活性化合物研發, 負責人, 地方任務, 2013-01--2016-12
( 4 ) 離子通道與膜轉運蛋白的的結構和新生物功能研究, 參與, 國家任務, 2012-01--2017-12
( 5 ) 新型抗癲癇藥物先導化合物 CF312 的結構最佳化及候選藥物的發現, 負責人, 國家任務, 2013-01--2016-12
( 6 ) 以鉀離子通道為靶點的神經系統疾病藥物研發, 參與, 國家任務, 2014-01--2016-12
( 7 ) 靶向離子通道電壓感受區治療神經興奮性升高疾病, 負責人, 國家任務, 2013-01--2016-12
( 8 ) 靶向離子通道電壓感受區治療神經興奮性升高疾病, 負責人, 國家任務, 2014-10--2017-09
( 9 ) 抗癲癇候選新藥HN37的臨床前開發, 負責人, 研究所自選, 2015-08--2016-12
( 10 ) 膜蛋白配體發現和新的生物學功能研究, 負責人, 國家任務, 2013-01--2017-08
參與會議
(1)Grafting voltage sensitivity in potassium channels 第61屆生物物理年會 2017-02-12
(2)Activation of Peripheral KCNQ Channels Relieves Gout Pain 亞洲疼痛年會 2015-11-10
(3)Development of antiepilepsy drug candidates targeting ion channels. 中以神經科學研討會 2015-04-06
(4)PIP2 alters pharmacological selectivity for epilepsy-causing KCNQ channels by dynamically interacting with voltage sensor elements Pingzheng Zhou 2014-08-02
(5)PIP2 alters pharmacological selectivity of epilepsy-causing KCNQ channels Pingzheng Zhou 2014-03-13
(6)The gating charge pathway of an epilepsy-associated potassium channel accommodates chemical ligands Ping Li 2013-07-02
(7)PIP2 alters pharmacological selectivity for epilepsy-causing KCNQ channels Pingzheng Zhou 2013-06-02
(8)Molecular structural basis of TRPA1 channel rectification 第九屆全國鈣信號和細胞功能研討會 Xia Wan 2012-07-16
(9)Chemical activation of voltage-gated potassium channels 中國神經科學會第九屆全國學術會議 Zhaobing Gao, Min Li 2011-07-29
(10)Chemical activation of voltage-gated potassium channels Zhaobing Gao, Min Li 2011-07-24
代表論文
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.