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课题组简介

已退休教授

于英心教授

   

    1.个人简介：

      王克威，博士，原北京大学药学院药理学系教授，系主任，兼神经生物学教授，北京大学麦戈文脑研究所首席研究员，长江学者, 教育部创新团队带头人。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年底回国后，获得了国家自然科学重点、面上基金、科技部863、973、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Neuron、Nature Neurosci、Nature和PNAS等杂志发表论文60余篇、专著章节3部和专利申请7份。
 

    2. 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：

    ★ KCNQ及TRP通道在神经精神疾病中的调节功能；

    ★ 离子通道调节剂的筛选与药理学研究；

    ★ 重症抑郁症(MDD)的离子通道机制；

    ★ Kv4钾通道与辅助蛋白KChIP相互作用的结构与功能研究。

     

    3. 科研项目：

    (1) Kv4钾通道与辅助蛋白KChIP相互作用的结构与功能研究；
(2) KCNQ/M-通道功能在神经精神疾病中的作用；
(3) 配体门控TRP通道的温度敏感机制和异源组装；
(4) 离子通道基因和蛋白表达与肿瘤的发生；
(5) 疾病组织中离子通道microRNA的鉴别、表达和功能
(6) 新药靶点的鉴别、确认和小分子化合物的筛选。

    4. 发表的主要论文：

    1. Flora Jow, Lan He, Angela Kramer, Joe Hinson, Mark R. Bowlby, John Dunlop and KeWei Wang (2006) “Validation of DRG-like F11 cells for evaluation of KCNQ/M-channel modulators”, Assay & Drug Dev Technologies 4(1):235-242.

    2.  Flora Jow, Eugene Tseng, Taney Maddox, Ru Shen, Dianne Kowal, John Dunlop, Belew Mekonnen and KeWei Wang (2006) “Rb+ efflux through functional activation of cardiac KCNQ1/minK channels by R-L3 benodiazepine compound”, Assay & Drug Dev Technologies 4(4):443-450.

    3.  Huayi Wang, Yan Yan, Qun Liu, Yanhua Huang, Yue Shen, Linjie Chen, Yi Chen, QiuyueYang, Quan Hao, KeWei WangCA and Jijie ChaiCA (2007) “Structural Basis for Modulation of Kv4 K+ Channels by Auxiliary KCHIP Subunits”, Nature Neuroscience 10 (1): 32-39.

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

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

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

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

    8.  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.

    9.   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.

    10. 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.

    11. 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.

    12.  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.

    13.  Wen Xu, Yuwei Wu, Yeping Bi, Lei Tan, Yehua Gan and KeWei WangCA (2010)“Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats”, Mol Pain, 6:49.

    14. Jinlong Qi, Fan Zhang, Yi Mi, Yan Fu, Wen Xu, Diqun Zhang, Yibing Wu, Xiaona Du, KeWei WangCA, Hailin ZhangCA (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. 2011 Mar; 46(3):934-43. Epub 2011 Jan 22.

    15. 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.

    16  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.

    17. 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.

    18. 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.

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

    20. Yuanyuan Cui, Fan Yang, Xu Cao, Vladimir Yarov-Yarovoy, KeWei WangCA, and Jie ZhengCA (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.

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

    22.  Xu Cao, Fan Yang, Jie ZhengCA and KeWei WangCA (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.

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

    24. Limin Shi, Xiling Bian, Zhiqiang Qu, Zegang Ma, Yu Zhou, KeWei WangCA, Hong JiangCA, Junxia XieCA (2013) Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels, Nature Communications 10.1038/ncomms2431.

    25.  Hu Z, Bian X, Liu X, Zhu Y, Zhang X, Chen S, Wang K, Wang Y (2013), Honokiol protects brain against ischemia-reperfusion injury in rats through disrupting PSD95-nNOS interaction, Brain Res,.1491: p. 204-12.

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

    27. Xiling Bian and KeWei Wang (2013) Targeting voltage-gated Kv7/KCNQ/M-channel for therapeutic potential of neuropsychiatric disorders, Journal of Chinese Pharmaceutical Sciences (English), invited review, in press.

    29.   KeWei Wang (2013) Drugs Targeting Ion Channels, book chapter in Handbook of Ion channels, in press.

    30.  Tianyang Ma, Bochuan Teng1, 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.

    31. 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, in press.

    32. 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 and Cell, in press.

    5. 获奖情况：


  •             2011-2013北京大学优秀博士研究生论文导师奖、


  •             2011年北京大学优秀教学奖、


  •             2010教育部自然科学奖、


  •             2009国务院侨办第二届百名华侨华人专业人士“杰出创业奖”、


  •             2007北京市教育创新标兵以及2005年中国教育部长江学者奖励计划等奖励。

     

    6. 招收和毕业的研究生情况：


  •             本科生9名：陈怡，阎焰，巩姗，董婧，卢卡，苏瑞锐，孙威，杨晨颖，刘佛根


  •             硕士生2名：陈辉，彭辉


  •             博士生11名：梁平，崔媛媛，许文，曹旭，毕野平，苏俊，张峰，孙威，卢彦欣，雷蕾，唐逸泉


  •             博士后3名：刘双，Sucana Simonic-Kocijan ，王莹

     

    7. 兼任学术职务情况：


  •             深圳北京大学-香港科技大学生物医学研究所副所长


  •             北京经济技术开发区生物医药产业顾问


  •             海南大学海洋药物教育部重点实验室学术委员会副主任


  •             福建师范大学福建省发育与神经生物学重点实验室第一届学术委员会副主任


  •             中国药理学会理事


  •             中国生物物理学会理事


  •             北京药学会理事


  •             北京药学会应用药理专业委员会副组委


  •             “Frontiers in Neuroscience”杂志编委


  •             “Pharmaceutica Sinica B”编委


  •             “药学学报”编委


  •             “中国药学”编委


  •             “神经药理学学报”编委