您目前的位置:首页 > 教授

王克威

?

王克威,博士,博士生导师,北京大学药学院365bet体育游戏_365线上体育_365体育投注+ribo88教授,兼神经生物学教授,北京大学麦戈文脑研究所首席研究员,教育部长江学者、创新团队带头人。1988年毕业于北京大学医学部并获神经生理学博士学位。1988年至1993年在剑桥大学作为博士后从事离子通道的生物物理学和药理学研究。1993年至1997年,在耶鲁大学生理系作为博士后及研究员,从事离子通道的结构与生物物理功能方面的研究。1997年至2005年间,在美国惠氏(Wyeth)制药公司(现合并为辉瑞Pfizer)神经科学研发部先后任高级和首席研究员并担任课题团队首席,从事新药靶点鉴别、优化、先导化合物筛选以及治疗癫痫、疼痛和神经精神等疾病的创新药物研发。

2005年底回国,获得了国家自然科学重点、面上基金、科技部863973、重大新药创制基金以及教育部985基金的支持。长期以来从事离子通道的神经生物学功能与创新药物研发的应用研究。在NeuronNature NeurosciNaturePNAS等杂志发表论文60余篇、专着章节3部和获得专利7份。

通讯地址:北京市海淀区学院路38号、国重2号楼3

邮编:100191

电话:(010)-8280 5065(办公室)-8280 5205(实验室)

传真:(010)-8280 5065

E-mail: wangkw@bjmu.edu.cn or wangkw@hsc.pku.edu.cn

?

研究领域:神经药理学和神经生物学

研究方向:离子通道的结构与神经生物学和神经药理学的功能以及靶向离子通道的新药研发。

细胞膜离子通道是神经电活动的物质基础,其功能异常致癫痫、慢性痛、抑郁症、学习与记忆障碍和精神分裂症等神经精神疾病。我们实验室采用细胞和脑片膜片钳等电生理学记录方法、结合分子生物学、生物化学和结构生物学手段,研究离子通道的分子调节机制以及离子通道的神经药理学与神经生物学功能。通过这些研究发现与确认新药靶标,筛选离子通道的调节剂及研发治疗神经精神疾病的创新药物。目前实验室主要研究电压门控Kv钾通道和瞬时受体电位配TRP两类离子通道,进行中的研究课题包括:

1KCNQTRP通道在神经精神疾病中的调节功能;

2、离子通道调节剂的筛选与药理学研究;

3、重症抑郁症(MDD)的离子通道机制;

4Kv4钾通道与辅助蛋白KChIP相互作用的结构与功能研究

目前获得的在研基金

1、获得2013-2017科技部973“重度抑郁症遗传与神经生物学基础及干预研究基金

2、获得2013-2015科技部创新药物与研发基金

3、获得2013-2014德国Bayer新药研发基金

4、获得2013-1016科技部重大新药创制科技重大专项:离子通道的靶标确认和候选药发现

5、获得2013-1017基金委创新研究群体基金精神疾病的神经可塑性机制

6、获得2014-1017国家自然科学面上基金辅助亚基KChIP调节Kv4通道的分子机制及功能意义研究

?近期发表的科研论

1.??????? Tianyang Ma, Bochuan Teng, Jinlong Qi, Hailin Zhang and KeWei Wang (2013) Development of HPLC assay for pharmacokinetic analysis of KCNQ/M-channel opener QO58-lysin in rat plasma, Journal of Chinese Pharmaceutical Sciences (English), in press

2.??????? Fan Yang, Linlin Ma, Xu Cao, KeWei Wang and Jie Zheng(2013) Divalent cations activate TRPV1 through promoting conformational change of the extracellular region, The Journal of General Physiology, in press

3.??????? Xu Cao, Linlin Ma, Fan Yang, KeWei Wang and Jie Zheng(2013) Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold, The Journal of General Physiology, in press

4.??????? Di-Jing Shi, Sheng Ye, Xu Cao, Rongguang Zhang and KeWei Wang (2013) Crystal structure of the N-terminal ankyrin repeat domain of TRPV3 reveals unique conformation of finger 3 loop critical for channel function, Protein & Cell DOI 10.1007/s13238-013-3091

5.??????? Zhang, Jing, Peng, Hui, Veasey, Sigrid C, Ma, Jing, Wang, Guang-Fa and Wang, Ke-Wei (2013) “Blockade of Na/H exchanger type 3 causes intracellular acidification and hyperexcitability via inhibition of pH-sensitive K channels in chemosensitive respiratory neurons of the dorsal vagal nucleus in rats”, Neurosci Bull 10.1007/s12264-013-1373-4

6.??????? Yanxin Lu, Xupeng Yue, Yuanyuan Cui, Jufeng Zhang and KeWei Wang (2013) MicroRNA-124 suppresses growth of human hepatocellular carcinoma by targeting STAT3, Journal of Biochemical and Biophysical Research Communications http://dx.doi.org/10.1016/j.bbrc.2013.10.157

7.??????? Yi-Quan Tang, Ping Liang, Jingheng Zhou, Yanxin Lu, Lei Lei, Xiling Bian and KeWei Wang (2013) Auxiliary KChIP4a Suppresses A-type K+ Current through ER Retention and Promoting Closed-state Inactivation of Kv4 Channels, J Biol Chem 288 (21):14727–14741

8.??????? Lei Lei, Xu Cao, Fan Yang, Di-Jing Shi, Yi-Quan Tang, Jie Zheng and KeWei Wang (2013) A TRPV4 channel C-terminal folding recognition domain critical for trafficking and function, J Biol Chem, March 2, 2013, DOI 10.1074/jbc.M113.457291

9.??????? Limin Shi, Xiling Bian, Zhiqiang Qu, Zegang Ma, Yu Zhou, KeWei Wang, Hong Jiang, Junxia Xie (2013) Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels, Nature Communications 10.1038/ncomms2431

10.??? Wen Liu, Min Lu, Bogang Liu, Yi Huang and KeWei Wang(2012) Inhibition of Ca2+-activated Cl- channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma, Cancer Letters, 326:41-51

11.??? Xu Cao, Fan Yang, Jie Zheng? and KeWei Wang? (2012) Intracellular proton-mediated activation of TRPV3 channels accounts for exfoliation effect of alpha hydroxyl acids on keratinocytes, J Biol Chem 287: 25905-25916, [Epub ahead of print] as Manuscript M112.364869, 2012 June 7

12.??? KeWei Wang and Yun Wang (2012) Negative modulation of NMDA receptor channel function by DREAM/calsenilin/KChIP3 provides neuroprotection?, Frontiers in Molecular Neuroscience, March 2012, volume 5, doi:10.3386/fnmol.2012.00039

13.??? Yuanyuan Cui, Fan Yang, Xu Cao, Vladimir Yarov-Yarovoy, KeWei Wang?, and Jie Zheng? (2012) “Selective Disruption of High-Sensitivity Heat Activation but Not Capsaicin Activation of TRPV1 Channels by Pore Turret Mutations”, Journal General Physiology, 139(4):273-283

14.??? Wei Cheng, Fan Yang Shuang Liu, Craig K. Colton, Yuanyuan Cui, Xu Cao, Michael X. Zhu, Changsen Sun, KeWei Wang? and Jie Zheng? (2012) “Heteromeric Heat-Sensitive TRP Channels Exhibit Distinct Temperature and chemical activation”, J Biol Chem 287(10):7279–7288

15.??? Zhimiao Lin, Quan Chen, Mingyang Lee, Xu Cao,Jie Zhang, Donglai Ma,Long Chen, Xiaoping Hu, Huijun Wang, Xiaowen Wang, Peng Zhang, XuanzhuLiu, Liping Guan, Yiquan Tang, Haizhen Yang, Ping Tu, Dingfang Bu, Xuejun Zhu, KeWei Wang, Ruoyu Li and Yong Yang (2012) “Exome Sequencing Reveals OlmstedSyndrome as a Channelopathy Caused by Mutations in TRPV3”, American Journal of Human Genetics 90:558--564

16.??? Yeping Bi, Hui Chen, Jun Su, Xu Cao, Xiling Bian and KeWei Wang? (2011)” Visceral hyperalgesia induced by forebrain-specific suppression of native Kv7/KCNQ/M-current in mice”? Molecular Pain 7:84, http://www.molecularpain.com/content/7/1/84

17.??? Jun Su, Xu Cao and KeWei Wang? (2011) “A novel degradation signal derived from distal C-terminal frame-shift mutations of KCNQ2 which cause neonatal epilepsy” J Biol Chem 286 (50):42949-42958

18.??? Feng Zhang, Shuang Liu, Fan Yang, Jie Zheng and KeWei Wang? (2011) “Identification of a tetrameric assembly domain in the C-terminus of heat-activated TRPV1 channels”,? J Biol Chem 286(17):15308–15316

19.??? Jinlong Qi, Fan Zhang, Yi Mi, Yan Fu, Wen Xu, Diqun Zhang, Yibing Wu, Xiaona Du, KeWei Wang?, Hailin Zhang? (2011) “Design, synthesis and biological activity of pyrazolo[1,5-a]pyrimidin-7(4H)-ones as novel Kv7/KCNQ potassium channel activators”, Eur J Med Chem. 46(3):934-43

20.??? Wen Xu, Yuwei Wu, Yeping Bi, Lei Tan, Yehua Gan and KeWei Wang(2010)

21.??? “Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats”, Mol Pain, 6:49

22.??? Fan Yang, Yuanyuan Cui, KeWei Wang and Jie Zheng (2010) “Is the pore turret just thermoTRP channels’ appendix?” PNAS 107 (32) E126-E127; published ahead of print July 21, 2010, doi:10.1073/pnas.1008504107

23.??? Ying Zhang, Ping Su, Ping Liang, Tao Liu, Xu Liu, Xin-Ying Liu, Bo Zhang, Tao Han, Yan-Bing Zhu, Dong-Min Yin, Jun-Fa Li, Zhuan Zhou, KeWei Wang, and Yun Wang (2010) “The DREAM Protein Negatively Regulates the NMDA Receptor through Interaction with the NR1 Subunit”, ?J Neurosci 30 (22):7525-7586.

24.??? Fan Yang, Yuanyuan Cui, KeWei Wang and Jie Zheng (2010) “Thermosensitive TRP Channel Pore Turret Is Part of the Temperature Activation Pathway”,? PNAS, 107 (15):7083-7088.

25.??? Ping Liang, Hao Chen, Yuanyuan Cui, and KeWei Wang (2010) “Functional Rescue of Kv4.3 Channel Tetramerization Mutants by KChIP4a”, Biophys J, 98 (12):2867-2876.

26.??? Yu-wei Wu Ye-Ping Bi, Xiao-Xing Kou, Wen Xu, Li-Qun Ma, Ke-Wei Wang,Ye-Hua Gan, Xu-Chen Ma (2010) “17-β-estradiol Enhanced Allodynia of Inflammatory Temporomandibular Joint through upregulation of Hippocampal TRPV1 in Ovariectomized Rats”, J Neurosci, 30(26)8710-9719.

27.??? Ping Liang, Huayi Wang, Hao Chen, Yuanyuan Cui, Lichuan Gu, Jijie Chai, and KeWei Wang? (2009) “Structural insights into KChIP4a modulation of Kv4.3 inactivation”, J Biol Chem, 284 (8): 4960-7

28.??? KeWei Wang and Jijie Chai (2009), Invited book chapter: “Structural Basis for Auxiliary KChIP Modulation of Kv4 Channels”.? Wiley Publisher (New York)

29.??? KeWei Wang (2008) “Modulation by clamping: Kv4 and KChIP interactions” Neurochemical Research (10):1964-69.

30.??? Yuanyua Cui, Ping Liang and KeWei Wang (2008) “Enhanced trafficking of tetrameric Kv4.3 channels by KChIP1 clamping”, Neurochemical Research 33(10):2078-84.

?