KeWei Wang, M.D.& Ph.D. Professor and Chair
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Our overall research is directed towards understanding structure and molecular mechanisms of ion channels, and their neurological modulations in pain, epilepsy, and neuropsychiatric disorders. Using techniques of electrophysiology, molecular biology, protein biochemistry and structure biology, our recent efforts have focused on studying structural insights into molecular modulation of Kv4 channels by accessory subunit KChIPs, molecular mechanism for tetrameric assembly of thermoTRP channels, and identification/development of Kv7/KCNQ channel modulators.
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Recent publications 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. 31. Huayi Wang, Yan Yan, Qun Liu, Yanhua Huang, Yue Shen, Linjie Chen, Yi Chen, QiuyueYang, Quan Hao, KeWei Wang? and Jijie Chai (2007) “Structural Basis for Modulation of Kv4 K+ Channels by Auxiliary KCHIP Subunits”, Nature Neuroscience 10 (1): 32-39. |