一、PI简介
Nikita Gamper,男,英国利兹大学生物医学学院教授、博士生导师,mg游戏平台电子手机版下载基础医学院兼职教授、博士生导师。1995年获得俄罗斯圣彼得堡大学(St Petersburg State University)生物/生物化学学士及硕士学位(最优等荣誉);1999年获俄罗斯塞克诺夫进化生理/生化研究院(Sechenov Institute of Evolutionary Physiology and Biochemistry)博士学位。1999/6-2005/12在德国Tuebingen University和美国University of Texas Health Science Center at San Antonio进行博士后研究。自2010年与mg游戏平台电子手机版下载药理教研室合作,研究成果已在J Clin Invest、PNAS及Antioxid Redox Signal等高水平杂志发表。且因与我校科研工作者的成功合作被授予“河北省优秀百位外国专家”称号。
二、研究方向
Nikita Gamper教授长期从事神经生理学及神经系统疾病的分子机制研究,尤其致力于:疼痛的细胞、分子及基因水平的机制;离子通道的生理及病理学;神经元沟通及胞内信号转导;以及疼痛等神经系统疾病的新的治疗靶点的发现等。
目前主要项目包括:1.氧化剂和锌对M型K+通道的调节;2. M通道在癫痫和脑卒中中的神经保护作用;3. T型Ca2+通道在痛觉感觉神经元中的作用和调节;4.转录抑制因子在慢性疼痛中的作用;5.神经元Ca2+激活的Cl-通道及其在兴奋性和信号传导中的作用。
三、代表性论文
1 | Gamper N, Stockand J, Shapiro MS (2003) Subunit-Specific Modulation of KCNQ Potassium Channels by Src Tyrosine Kinase. J. Neurosci. 23, 84-95. |
2 | Gamper N, Reznikov V, Yamada Y, Yang J, Shapiro MS (2004) PIP2 signals underlie receptor-specific Gq/11-mediated modulation of N-type Ca2+ channels. J. Neurosci. 24, 10980-10992. |
3 | Delmas P, Coste B, Gamper N, Shapiro MS (2005) Phosphoinositide Lipid Second Messengers: New Paradigms for Calcium Channel Modulation. Neuron. 47, 179-182. |
4 | Gamper N. Li Y, Shapiro SM (2005) Structural requirements for subunit-specific modulation of KCNQ K+ channels by Ca2+/Calmodulin. Mol. Biol. Cell. 16, 3538-3551. |
5 | Li Y, Gamper N, Hilgemann DW, Shapiro MS (2005) Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol (4,5)-bisphosphate. J. Neurosci. 25, 9825-9835. |
6 | Patwardhan AM, Jeske NA, Price TJ, Gamper N, Akopian AN, Hargreaves KM (2006) The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. Proc. Natl. Acad. Sci. U. S. A. 103, 11393-8. |
7 | Gamper N, Zaika O, Li Y, Martin P, Hernandez CC, Perez MR, Wang AY, Jaffe DB, Shapiro MS (2006) Oxidative modification of M-type K+ channels as a mechanism of cytoprotective neuronal silencing. EMBO J. 25, 4996-5004. |
8 | Gamper N, Shapiro MS (2007). Regulation of ion transport proteins by membrane phosphoinositides. Nat. Rev. Neurosci. 8:921-934. |
9 | Linley JE, Rose K, Patyl M, Robertson B, Akopian AN, Gamper N (2008) Inhibition of M Current in Sensory Neurons by Exogenous Proteases: a Signalling Pathway Mediating Inflammatory Nociception. J. Neurosci. 28, 11240-11249. |
10 | Milligan CJ, Li J, Sukumar P, Majeed Y, Dallas ML, English A, Emery P, Porter KE, Smith AM, McFadzean I, Beccano-Kelly D, Bahnasi Y, Cheong A, Naylor J, Zeng F, Liu X, Gamper N, Jiang L-H, Pearson HA, Peers C, Robertson B, Beech DJ (2009). Robotic multi-well planar patch-clamp for native and primary mammalian cells. Nature Protocols 4, 244-55. |
11 | Liu B, Linley JE, Du X, Zhang X, Ooi L, Zhang H, Gamper N(2010) Ionic Mechanisms for the Acute Nociceptive Signals Induced by Bradykinin in Rat Sensory Neurons. J Clin Invest 120, 1240-52. |
12 | Mucha M, Ooi L, Linley J, Mordaka P, Dalle C, Robertson B, Gamper N, Wood IC (2010) Transcriptional control of KCNQ channel genes and the regulation of neuronal excitability. J Neurosci. 30, 13235-45. |
13 | Rose K, Ooi L, Dalle C, Robertson B, Wood IC, Gamper N (2011) Transcriptional repression of the M channel subunit Kv7.2 in chronic nerve injury. PAIN 152,742-54. |
14 | Linley JE, Ooi L, Pettinger L, Kirton H, Boyle JP, Peers C, Gamper N (2012) Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons. Proc Natl AcadSci U S A. 109, E1578-86. |
15 | Jin X, Shah S, Liu Y, Zhang H, Lees M, Fu Z, Lippiat JD, Beech DJ, Sivaprasadarao A, Baldwin SA, Zhang H, Gamper N (2013) Activation of the Cl- Channel ANO1 by Localized Calcium Signals in Nociceptive Sensory Neurons Requires Coupling with the IP3 Receptor. Sci Signal. 6(290):ra73. |
16 | Ooi L, Gigout S, Pettinger L, Gamper N (2013) Triple cysteine module within M-type K+ channels mediates reciprocal channel modulation by nitric oxide and reactive oxygen species. J Neurosci. 33:6041-6. |
17 | Pettinger L, Gigout S, Linley JE, Gamper N (2013) Bradykinin controls pool size of sensory neurons expressing functional d-opioid receptors. J Neurosci. 33:10762-71. |
18 | Du X, Hao H, Gigout S, Huang D, Yang Y, Li L, Wang C, Sundt D, Jaffe DB, Zhang H, Gamper N (2014) Control of Somatic Membrane Potential in Nociceptive Neurons and its Implications for Peripheral Nociceptive Transmission. PAIN 155:2306-22. |
19 | Parry DA, Holmes TD, Gamper N, El-Sayed W, Hettiarachchi NT, Ahmed M, Cook GP, Logan CV, Johnson CA, Joss S, Peers C, Prescott K, Savic S, Inglehearn CF, Mighell AJ.(2016) A homozygous STIM1 mutation impairs store-operated calcium entry and natural killer cell effector function without clinical immunodeficiency. J Allergy ClinImmunol. 137:955-7. |
20 | Huang D, Huang S, Gao H, Liu Y, Qi J, Chen P, Wang C, ScraggJL, Vakurov A, Peers C, Du X, Zhang H, Gamper N (2016) Redox-dependent modulation of t-type Ca2+ channels in sensory neurons contributes to acute anti-nociceptive effect of substance P. Antioxid Redox Signal. 25:233-51. |
21 | Du X, Hao H, Yang Y, Huang S, Wang C, Gigout S, Ramli R, Li X, Jaworska E, Edwards I, Deuchars J, Yanagawa Y, Qi J, Guan B, Jaffe DB, Zhang H, Gamper N (2017) Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission. J Clin Invest. 127:1741-1756. |
22 | Gao H, Boillat A, Huang D, Liang C, Peers C, Gamper N (2017) Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate. Proc Natl AcadSci U S A. 114:E6410-E6419. |
23 | Berrout J, Kyriakopoulou E, Moparthi L, Hogea AS, Berrout L, Ivan C, Lorger M, Boyle J, Peers C, Muench S, Elies J, Hu X, Hurst C, Hall T, Umamaheswaran S, Wesley L, Gagea M, Shires M, Manfield I, Knowles MA, Davies S, Suhling K, Gonzalez YT, Carragher N, Macleod K, Abbott J, Calin JA, Gamper N, Zygmunt PM, Timsah Z (2017) TRPA1- FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p. Nat Commun. 8:947. |
24 | Zhang F, Wang Y, Liu Y, Han H, Zhang D, Fan X, Du X, Gamper N, Zhang H. (2019) Transcriptional Regulation of Voltage-Gated Sodium Channels Contributes to GM-CSF-Induced Pain.J Neurosci. 39:5222-33. |
25 | Zhang F, Gigout S, Liu Y, Wang Y, Hao H, Buckley NJ, Zhang H, Wood IC, Gamper N. (2019) Repressor element 1-silencing transcription factor drives the development of chronic pain states.PAIN 160:2398-2408. |
四、承担课题
(一)Wellcome Trust Investigator award 212302/Z/18/Z “Peripheral gate in somatosensory system” 01/10/2018 – 31/09/2023. £1,141,006 awarded to Nikita Gamper (PI).
(二)National Natural Science Foundation of China Project grant “Augmentation of M channel Activity by intracellular zinc as novel neuroprotective mechanism” 01/01/2019 – 31/12/2022. RMB 560,000 awarded to Haixia Gao (PI) and Nikita Gamper (Co-I).
(三)BBSRC International Partnering Awards BB/R02104X/1 “Emerging Approaches to Intracellular Signaling” 02/07/2018 – 01/062022. £30,000 awarded to Nikita Gamper (PI) and Stephen Muench (Co-I).
(四)BBSRC Project Grant BB/R003068/1 “Junctional multiprotein signaling complexes in sensory neurons” 01/10/2017 – 30/09/2020. £622,032 awarded to Nikita Gamper (PI).
(五)MRC Training grant MR/P015727/1 “Functional expression of M channel subunits in peripheral somatosensory system” 01/10/2017 – 30/09/2021. £130,431 awarded to Nikita Gamper (PI) and Emanuele Sher (Industrial partner).
五、团队人员组成及简介
(一)个人简介
Co-PI 杲海霞,女,教授,博士生导师。1994年获山东大学药学院药学学士学位;并于同年开始至今在mg游戏平台电子手机版下载药理教研室工作;期间于2004年获mg游戏平台电子手机版下载药理学硕士学位;2012年获mg游戏平台电子手机版下载药理学博士学位;并于2014-2016赴英国利兹大学进行博士后研究。
(二)研究方向
目前主要对钾离子通道和TRP通道在疼痛、脑缺血以及肿瘤增殖迁移中的作用进行研究。主要涉及电生理学、成像学、分子生物学和细胞生物学等实验技术。
(三)代表文章
1 | Gao H, Boillat A, Huang D, Liang C, Peers C, Gamper N.Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate.Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):E6410-E6419. |
2 | Gao H, Chen X, Du X, Guan B, Liu Y, Zhang H. EGF enhances the migration of cancer cells by up-regulation of TRPM7. Cell Calcium. 2011 Dec;50(6):559-68. |
3 | Ge Y, Wang Y, Chen P, Wang Y, Hou C, Wu Y, Zhang M, Li L, Huo C, Shi Q, Gao H *.Polyhydroxytriterpenoids and Phenolic Constituents from Forsythia suspensa (Thunb.) Vahl Leaves. J Agric Food Chem. 2016 Jan 13;64(1):125-31. |
4 | Du X, Gao H, Jaffe D, Zhang H, Gamper N. M-type K+ channels in peripheral nociceptive pathways. Br J Pharmacol. 2017 Aug 11. |
5 | Huang D, Huang S, Gao H, Liu Y, Qi J, Chen P, Wang C, Scragg JL, Vakurov A, Peers C, Du X, Zhang H, Gamper N. Redox-Dependent Modulation of T-Type Ca(2+) Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P. Antioxid Redox Signal. 2016 Aug 10;25(5):233-51. |
6 | Dun J, Chen X, Gao H, Zhang Y, Zhang H, Zhang Y. Resveratrol synergistically augments anti-tumor effect of 5-FU in vitro and in vivo by increasing S-phase arrest and tumor apoptosis. Exp Biol Med (Maywood). 2015 Mar 2. |
7 | Zhao Z, Cui W, Zhang H, Gao H, Li X, Wang Y, Hu H, Li B.Pre-treatment of a single high-dose of atorvastatin provided cardioprotection in different ischaemia/reperfusion models via activating mitochondrial KATP channel. Eur J Pharmacol. 2015 Mar 15;751:89-98. |
(四)承担课题
1、缺血脑组织不同来源锌离子蓄积对M型钾离子通道的调节及其在缺血脑保护中的作用 国家基金 81871027 主持
2、TRPM7参与EGF诱导的肺腺癌细胞迁移的分子机制研究 国家基金 81201642 主持
3、CD147调控TRPM7促进胃癌细胞迁移的分子机制研究 国家基金 81572363 第二参与人