镇学初

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姓  名:镇学初
职称职务:特聘教授、院长
电子邮箱:zhenxuechu@suda.edu.cn
办公地址:云轩楼2017

个人简介
一、学习工作经历
1、学历背景:
1980.9-1985.7:湖北医科大学分院,医学学士
1985.9-1988.7:西安交通大学,医学硕士
1992.2-1996.6:瑞士日内瓦大学,医学博士
2、国外学习研究经历:
1996.7-1998.12:宾夕法尼亚医学院药理系,博士后
1999.1-2000.12:美国宾西法尼亚州立大学医学院,博士后
3、工作经历:
1988.9-1992.1:北京酒仙桥医院(现清华大学第一附属医院),主治医师、副主任医师
2001.1-2003.12:费城Drexel大学医学院药理系,助理教授
2004.1-2006.7:纽约城市大学医学院药理系,副教授
2006.7-2010.5:中科院上海药物研究所,研究员课题组长
2010.5至今:苏州大学药学院,特聘教授、院长
二、研究方向
(1)靶向神经精神重大疾病的药物研发:以精神分裂症、帕金森氏病、抑郁症、药物成瘾为靶向,寻找和发现新型小分子药物。
(2)神经递质受体调控及信号传导机制:研究神经递质特别是多巴胺受体信号及功能调控的分子机制,并探讨其在重大神经精神疾病中的作用和机理。
(3)胶质细胞及神经免疫:研究胶质细胞功能调控的机制,及其在生理病理条件下的作用,神经免疫与胶质功能调控。
三、主要研究成果
主要从事精神神经药理研究及相关药物研发,发表SCI论文60余篇。申请中国专利13项,已授权2项。先后主持科技部863、国家杰出青年科学基金、国家自然科学基金、国家重大专项新药创制项目。
1、论文
(1)    Guo L, Zhao J, Jin G, Zhao B, Wang G, Zhang A, Zhen X. SKF83959 is a Potent Allosteric Modulator of Sigma-1 Receptor. Mol Pharmacol. 2013 ;83(3):577-86
(2)    Zhang L, Fan H, Lu R, Xin Y, Zhen X, Liu Z. CMYA5: a new potential substrate of Kcna3 in human heart. Biochem Biophys Res Commun. 2013 45(3):236-8
(3)    Mao L, Jia J, Zhou X, Xiao Y, Wang Y, Mao X, Zhen X, Guan Y, Alkayed NJ, Cheng J. Delayed administration of a PTEN inhibitor BPV improves functional recovery after experimental stroke.Neuroscience. 2013 Feb 12;231:272-81
(4)    Xu L, Li Y, Sun H, Zhen X, Qiao C, Tian S, Hou T. Current developments of macrophage migration inhibitory factor (MIF) inhibitors. Drug Discov Today. doi: 10.1016/j.drudis.2012.12.013. [Epub ahead of print]
(5)    Ye N, Neumeyer JL, Baldessarini RJ, Zhen X, Zhang A.Update 1 of: Recent Progress in Development of Dopamine Receptor Subtype-Selective Agents: Potential Therapeutics for Neurological and Psychiatric Disorders. Chem Rev. 2013 Mar 7. [Epub ahead of print].
(6)    Haifeng Suna, Liyuan Zhub, Huicui Yangc, Wangke Qiana, Lin Guob, Shengbin Zhoua, Bo Gaoc, Zeng Lia, Yu Zhoua, Hualiang Jianga, Kaixian Chena, Xuechu Zhen, Hong Liu Asymmetric Total Synthesis and Identification of Tetrahydroprotoberberine Derivatives as New Antipsychotic Agents Possessing a Dopamine D1, D2 and Serotonin 5-HT1A Multi-Action Profile. BIOORG. MED. CHEM. ;21(4):856-68
(7)    Liu CL, Gao M, Jin GZ, Zhen X. GABA Neurons in the Ventral Tegmental Area Responding to Peripheral Sensory Input. PLoS One. 2012;7(12):e51507. doi: 10.1371.
(8)    Qian W, Lu W, Sun H, Li Z, Zhu L, Zhao R, Zhang L, Zhou S, Zhou Y, Jiang H, Zhen X, Liu H. Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: selective inhibitors of dopamine D receptor. Bioorg Med Chem. 2012, 20(15):4862-71.
(9)    Zheng YY, Guo L, Zhen XC, Li JQ. Synthesis and antidepressant activity of arylalkanol-piperidine derivatives as triple reuptake inhibitors. Eur J Med Chem. 2012, 54:123-36.
(10)Xu Z, Dong S, Du D, Jiang N, Sun P, Wang H, Yin L, Zhang X, Cao X, Zhen X, Hu Y. Generation and characterization of hD(5) and C-terminal Mutant hD(5m) transgenic rats. Brain Res. 2012, 1448:27-41.
(11)Chu HY, Wu Q, Zhou S, Cao X, Zhang A, Jin GZ, Hu GY, Zhen X. SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor-independent mechanism. J Neurosci Res. 2011 Aug;89(8):1259-66.
(12)Zhang H, Ye N, Zhou S, Guo L, Zheng L, Liu Z, Gao B, Zhen X, Zhang A. Identification of N-Propylnoraporphin-11-yl 5-(1,2-Dithiolan-3-yl)pentanoate as a New Anti-Parkinson's Agent Possessing a Dopamine D(2) and Serotonin 5-HT(1A) Dual-Agonist Profile. J Med Chem. 2011 Jun 14. 54(13):4324-38.
(13)Ye N, Wu Q, Zhu L, Zheng L, Gao B, Zhen X, Zhang A. Further SAR study on 11-O-substituted aporphine analogues: Identification of highly potent dopamine D(3) receptor ligands. Bioorg Med Chem. 2011 Mar 15; 19(6):1999-2008.
(14)Chu HY, Yang Z, Zhao B, Jin GZ, Hu GY, Zhen X*. Activation of phosphatidylinositol-linked D1-like receptors increases spontaneous glutamate release in rat somatosensory cortical neurons in vitro. Brain Res. 2010 Jul 9; 1343:20-7.
(15)Mo J, Zhang H, Yu LP, Sun PH, Jin GZ, Zhen X. L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease. Neurobiol Aging. 2010 Jun; 31(6):926-36.
(16)Chu HY, Zhen X. Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels in the regulation of midbrain dopamine systems. Acta Pharmacol Sin. 2010 Sep; 31(9):1036-43.
(17)Chu HY, Gu QH, Jin GZ, Hu GY, Zhen X. Electrophysiological Effects of SKF83959 on Hippocampal CA1 Pyramidal Neurons: Potential Mechanisms for the Drug’s Neuroprotective Effects. PlosOne. 2010 Oct 1; 5(10): e13118.
(18)Gao M, Chu HY, Jin GZ, Zhang ZJ, Wu J, Zhen X. l-Stepholidine-induced excitation of dopamine neurons in rat ventral tegmental area is associated with its 5-HT(1A) receptor partial agonistic activity. Synapse.2011 May; 65(5):379-87.
(19)Zhao T, Liu X, Zhen X, Guo SW. Levo-Tetrahydropalmatine (l-THP) Retards the Growth of Ectopic Endometrial Implants and Alleviates Generalized Hyperalgesia in Experimentally Induced Endometriosis in Rats. Reprod Sci. 2011 Jan; 18(1):18-45.
(20)Wu C, Yang K, Liu Q, Wakui M, Jin GZ, Zhen X, Wu J. Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta. Neuropharmacology. 2010 Dec; 59(7-8):567-72.
(21)Liu Z,Zhang H, Yu LP, Zhen X, Zhang A. Synthesis of Furo[3,2-l]aporphine and Dihydrofuro[3,2-l]aporphine Derivatives: Identification of a Potent and Selective 5-HT1A Receptor Agonist.  J. Med. Chem. 2010 Feb 11; 53(3):1319-28.
(22)Zhang J, Zhang H, Cai W, Yu L, Zhen X, Zhang A. 'Click' D(1) receptor agonists with a 5-HT(1A) receptor pharmacophore producing D(2) receptor activity. Bioorg Med Chem.2009 Jul 15; 17(14):4873-80.
(23)Zhang X, Fei Ding, Zhen X, Jiawei Zhou. PI-linked D1 receptor-Mediated FGF-2 Expression in Astrocytes Protects Dopaminergic Neurons. J. Neurosci. 2009, 29(24):7766-75.
(24)Guo Y, Zhang H, Chen X, Cai W, Cheng J, Yang Y, Jin G, Zhen X. Evaluation of the a antipsychotic effect of bi-acetylated l-stepholidine (l-SPD-A), a novel dopamine and serotonin receptor dual ligand. Schizophrenia Res. 2009 Nov; 115(1):41-9.
(25) Sun P, Wang J, Gu W, Cheng W, Jin GZ, Friedman E, Zheng J, Zhen X. PSD-95 regulates D1 dopamine receptor resensitization, but not receptor-mediated Gs-protein activation. Cell Res. 2009 May; 19(5):612-24.
(26)Chen XQ, Zhang J, Neumeyer JL, Jin GZ, Hu GY, Zhang A, Zhen X. Arylbenzazepines are potent modulators for the delayed rectifier K+ channel: a potential mechanism for their neuroprotective effects. PLoSOne. 2009 Jun 5; 4(6):e5811.
(27)Yang K, Hu J, Lucero L, Liu Q, Zheng C, Zhen X, Jin G, Lukas RJ, Wu J. Distinctive nicotinic acetylcholine receptor functional phenotypes of rat ventral tegmental area dopaminergic neurons. J Physiol. 2009 Jan 15; 587(Pt 2):345-61.
(28)Zhang J, Xiong B, Shen JK, Zhen X, Zhang A. Dopamine D1 Receptor Ligands: Where are we now and where are we going? Med. Res. Rev. 2009 Mar; 29(2):272-94.
(29)Chu HY, Jin GZ, Friedman E, Zhen X. Recent Development in Studies of Tetrahy droprotoberberines: Mechanism in Antinociception and Drug Addiction. Cell Mol Neurobiol. 2008 Jun; 28(4):491-9.
(30)Liu Z, Chen X, Yu L, Zhen X, Zhang A. Synthesis and pharmacological investigation of novel 2-aminothiazole-privileged aporphines. Bioorg Med Chem. 2008 Jul 15; 16(14):6675-81.
(31)Liu Z, Chen X, Sun P, Yu L, Zhen X, Zhang A. N-Propylnoraporphin-11-O-yl carboxylic esters as potent dopamine D(2) and serotonin 5-HT(1A) receptor dual ligands. Bioorg Med Chem. 2008 Sep 15; 16(18):8335-8.
(32)Zhang D, Zhang H, Jin GZ, Zhang K, Zhen X. Single dose of morphine produced a prolonged effect on dopamine neuron activities. Mol Pain. 2008 Nov 17; 17: 4-57.
(33)Zhang D, Yang S, Yang C, Jin G, Zhen X. Estrogen modulated cocaine-altered dopamine neuron activity in ventral tegmental area. Psychopharmacology. 2008, 199(4):625-35.
(34)Zhang J, Chen X, Yu L, Zhen X, Zhang A. Synthesis of 6-substituted 1-phenylbenzazepines and their dopamine D(1) receptor activities. Bioorg Med Chem. 2008 Nov1; 16(21):9425-31.
(35)Feng YQ, Zhou ZY, He X, Wang H, Guo XL, Hao CJ, Guo Y, Zhen X, Li W. Dysbindin deficiency in sandy mice causes reduction of snapin and displays behaviors related to schizophrenia. Schizophr Res. 2008 Dec; 106(2-3):218-28.
(36)Zhang ZJ, Tan QR, Tong Y, Li Q, Kang WH, Zhen X, Post RM. The effectiveness of carbamazepine in unipolar depression: a double-blind, randomized, placebo-controlled study. J Affect Disord. 2008 Jul; 109(1-2):91-7.
(37)Yu Y, Wang JR, Sun PH, Guo Y, Zhang ZJ, Jin GZ, Zhen X. Neuroprotective effects of atypical D1 receptor agonist SKF83959 are mediated via D1 receptor-dependent inhibition of glycogen synthase kinase-3beta and a receptor-independent anti-oxidative action. J Neurochem. 2008 Feb; 104(4):946-56.
(38)Mo J, Guo Y, Yang YS, GZ Jin, Zhen X. A novel dual dopamine D1 receptor agonist and D2 receptor antagonist: potential antipsychotic agents. Current Medical Chemistry. 2007, 14:2996-3002.
(39)Gu WH, Yang S, Shi WX, Jin GZ, Zhen XC. Requirement of PSD-95 for dopamine D1 receptor modulating glutamate NR1a/NR2B receptor function. Acta Pharmacol Sin. 2007 Jun; 28(6):756-62.
(40)Tan QR, Wang XZ, Wang CY, Li XJ, ChenY,Wang HH,Zhen X and Zhang ZJ. Differential effects of atypical and classical antipsychotics in protecting against neurotoxicity induced by rotenone in PC12 cells. Eur Neuropsychopharmacol. 2007, 17(12):768-73.
(41)Zhen X, Goswami S, Abdali SA, Frankfurt M, Friedman E. Estrogen-modulated frontal cortical CaMKII activity and behavioral supersensitization induced by prolonged cocaine treatment in female rats. Psychopharmacology (Berl). 2007 Apr; 191(2):323-31.
(42)Zhang H, Wang F, Chen J, Zhen X. SKF83959 attenuated L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson’s disease. Neuropharmacology. 2007 Jul; 53(1):125-33.
(43)Mo J, Guo Y, Yang YS, Shen JS, Jin GZ, Zhen X. Recent developments in studies of l-stepholidine and its analogs: chemistry, pharmacology and clinical implications. Curr Med Chem. 2007, 14(28):2996-3002.
(44)GU W, Shi WX, Zhen X, Jin G. Effects of (-) -stepholidineon NMDA receptors; comparison with haloperidol and clozapine. Acta Pharmacologica Sinica. 2007 Jul; 28(7):953-8.
(45)Gu W, Shi WX, Jin G, Zhen X. Requiring PSD-95 for D1 dopamine receptor modulating NMDA receptor function. Acta Pharmacologica Sinica. 2007, 28(6):756-62.
(46)Gao M, Liu CL, Yang S, Zhen X, Jin GZ. l-Stepholidine increases the frequency of sEPSC via the activation of D1 dopamine signaling pathway in rat prelimbic cortical neurons. Acta Pharmacol Sin. 2007 May; 28(5):627-33.
(47)Ming Y, Zhang H, Long L, Wang F, Chen J, Zhen X. Modulation of Ca2+ signals by phosphatidylinositol-linked novel D1 dopamine receptor in hippocampal neurons. J Neurochem. 2006 Aug; 98(4):1316-23.
(48)Zhen X, S Gaswomi, E Friedman. Estrogen-modulated frontal cortical CaMKII activity is involved in behavioral supersensitization to cocaine in female rats. Psychopharmacology. 2007 Apr; 191(2):323-31.
(49)Yuling Ming, Hai Zhang, J Chen, Zhen X. SKF83959 stimulates Ca2+ signaling in primary cultured hippocampal neurons. J. Neurochem. 2005, 98:1316-23.
(50)Zhang-Jin Zhang, Xiao-Long Jiang, Steven E. Zhang, Yan Zhang, Christopher J. Hough, He Li, Zhen X*. The paradoxical effects of SKF83959, a novel dopamine D1-like receptor agonist, in the rat acoustic startle reflex paradigm. Neurosci. Lett.2005 Jul; 382(1-2):134-8.
(51)Zhen X, Satindra Goswami. Activation of Phosphatidyinositol (PI)-linked D1 Dopamine Receptor Is Associated With The Antiparkinsonian Action of SKF83959. Biochem. Pharm. Behav. 2005, 80(4):597-601.
(52)Zhen X, Gaswomi S, abdali SA. Regulation of cdk5 and CaMKII by PI-linked dopamine receptor in rat brain. Mol Pharmacol. 2004 Dec; 66(6):1500-7.
(53)M Gil, Zhen X. Prenatal cocaine exposure alters GSK3β pathways in select rabbit brain areas. Neurosci Lett. 2003 Oct 9; 349(3):143-146.
(54)LQ Jin, Gaswami S, Zhen X. SKF83959 selectively regulates phosphatidylinositol-linked D1 dopamine receptors in rat brain. J. Neurochem. 2003 Apr; 85(2):378-86.
(55)Zhen X*, C Torries, GP Cai, et al. Inhibition of striatal protein tyrosine phosphatases is associated with D2 dopamine receptor-mediated supersensitivity in Parkisno’s rat model. Mol. Pharmacol. 2002, 62:1356-1362.
(56)Zhen X, C Torries, E Friedman. Lithium regulates tyrosine phosphatase activity in vivo and in vitro. Psychopharm. 2002 Aug; 162(4):379-84.
(57)Zhen X, Claudio Torres, Hoau-Yan Wang. Prenatal exposure to cocaine disrups D1A dopamine receptor function via selective inhibition of protein phosphatase 1 pathway in rabbit frontal cortex. J. Neurosci. 2001 Dec 1; 21 (23): 9160-67.
(58)Zhen X, J Zhang, E Friedman. D4 dopamine receptor differentially regulates Akt/NF-kB pathways in D4MN9D cells. Mol.Pharmacol. 2001 Oct; 60(4):857-64.
(59)J Yu, Reilly G, Zhen X, CE Yellowley, CR Jacobs. Osteopontin gene regulation by oscillatory fluid flow via intracellular calcium mobilization and activation of mitogen-activated protein kinase in MC3T3-E1 cells. J. Biol. Chem. 2001 Apr 20; 276(16):13365-13371.
(60)Zhen X, W Du, R Anthony, E Friedman and J Harvey. The p38 MAPK is involved in associative learning in rabbits. J. Neurosci. 2001 Aug 1; 21(15): 5513-9.
(61)Zhen X*, Wu Q and Q Chen. Role of p38 MAPK in PTH-regulated chondrocyte differentiation. J. Biol. Chem. 2001, 276:4879-85.
(62)Zhen X, GP Cai (co-first author), K Uryu, E Friedman. Activation of extracellular signal-regulated protein is associated with sensitized locomotive response to D2 dopamine receptor stimulation in unilateral 6-hydroxydopamine-lesioned rats. J. Neurosci. 2000 Mar 1; 20(5):1849-1857.
(63)Zhen X, K Uryu, GP Cai, J Johnson, E Friedman. Age-related impairment of MAP kinase and effect of caloric restriction in brains of Fisher 344 rats. J. Gerontol. 1999, 54A:B539-548.
(64)Zhen X, K Uryu, HY Wang and E Friedman. D1 dopamine receptor agonists mediate activation of p38 MAPK and JNK by a protein Kinase A-dependent mechanism in SK-N-MC cells. Mol. Pharmacol. 1998 Sep, 54(3):453-458.
(65)Zhen X, JP Bonjour and J Caverzasio. Platelet-derived growth factor stimulates sodium-dependent Pi transport in osteoblastic cells via phospholipase C and phosphatidylinositol 3’kinase. J. Bone & Mineral Res. 1997, 12:35-42 .
(66)Imai, Zhen X, JP Bonjour and J Carverzasio. Aluminum potentiates Pi transport stimulation induced by fluoride in osteoblast-like cells. Am. J. Physiol. 1996, 271(Endocrinol. Metab.34): E694-701.
2、课题 
在研项目:
(1)精神分裂症前额叶功能紊乱的机制(NFSC重点项目,2011-2016),基金委,主持人,81130023
(2)973项目“阿片类物质精神依赖的神经生物学机制”(2008-2013),科技部,课题骨干,2009CB52200
(3)973项目“胶质细胞与神经损伤和修复”(2010-2015),科技部,课题骨干,2011CB5C4403
 
已结题项目:
(1)863项目“磷脂肌醇(PI)-偶联的新型多巴胺受体基因及功能研究”(2007-2011),科技部,主持人,2007AA02Z163
(2)国家重大专项“THPB-d抗精神分裂症作用的临床前研究项目”(2009-2011),主持人, 2009ZX09102-023
(3)自然科学基金面上项目“锚锭蛋白PSD-95 调节多巴胺D1 受体功能的分子机制”(2007-2010)基金委,主持人,30770662
(4)国家杰出青年基金“神经精神药理学研究”(2008-2012),主持人,30825042
(5)上海浦江人材计划(2007-2009),25万,上海市科委,主持人,07PJ141050
(6)973项目“精神活性物质成瘾机理及干预”(2006-2008),106万,科技部,课题骨干,2003CB515401
(7)精神分裂症新机制研究(百人计划),270万,中科院、财政部,主持人,20070712
 (8)国家重大专项“抗PD新型化合物发现”(2009-2011),75万,科技部,Co-PI,2009ZX103-062
3、著作
(1)《脑内多巴胺》,上海科技出版社,主编:金国章,镇学初,2010.9。
(2)《高等药理学》,科技出版社,主编:丁键、镇学初,2013。
4、专利
(1)镇学初,程建军,郭扬,莫骄,杨玉社,金国章,嵇汝运:左旋千金藤啶碱(l-SPD)衍生物、其制备方法和用途。中国发明专利,已授权ZL2007 1 0039617.4.
(2)杨玉社,丁宇,孙佩华,莫骄,金国章,嵇汝运,镇学初:一类四氢原小檗碱类化合物、其制备方法及其组合物和用途。中国发明专利,已授权ZL2006 1 0029384.5.
(3)张翱,镇学初,刘治礼,张海:非儿茶酚类阿朴吗啡衍生物、其药物组合物及其用途。中国发明专利,专利号:200910048214.5.
(4)傅伟,镇学初:吲哚苯并噻唑类衍生物及药物用途。中国发明专利,专利号:CN201010256124.8.
(5)扬申,曹银祥,金国章,张叠,褚宏远,高明,镇学初:整体多位点同步记录及频谱分析与脑区功能联系监测系统及方法。中国发明专利,专利号:200810033267.5.
(6)张翱,镇学初,张静,陈学涛,余蕾平:一类新型苯并氮杂卓类化合物、制备方法及其用途。中国发明专利,专利号:200810200262.7.
(7)张翱,镇学初,刘志礼,冯林音:一类异喹啉化合物、制备方法及用途。中国发明专利:已授权,CN101311176-A.
(8)张翱,镇学初,刘致礼,陈学涛,余蕾平:阿朴吗啡类化合物、其药物组合物及其应用。中国发明专利,专利号:200810040230.5.
(9)左旋千金藤啶碱(l-SPD)衍生物的用途。中国发明专利,专利号:200810037617.5.
(10)张翱,镇学初,张静,陈学涛,余蕾平:New Benzazepine Compounds, Preparation Methods and Uses Thereof. (一类新型苯并氮杂卓类化合物、制备方法及其用途) PCT国际发明专利:PCT/CN2009/001068.
(11)镇学初,程建军,郭扬,莫骄,杨玉社,金国章,嵇汝运:L-Stepholidine(L-SPD)Derivatives, Preparation Method and Usage Thereof. (左旋千金藤啶碱(l-SPD)衍生物、其制备方法和用途) PCT国际发明专利:PCT/CN2008/000795.
(12)杨玉社,丁宇,孙佩华,莫骄,金国章,嵇汝运,镇学初:Tetrahydroprotoberberine Compounds, Their Manufacture, Medicinal Composition and Uses. (一类四氢小檗碱类化合物、其制备方法及其组合物和用途) PCT国际发明专利:PCT/CN2007/001734.
(13)柳红、镇学初、孙海丰、朱丽媛、钱王科、俞蕾平、栗增、蔡文贤、蒋华良、陈凯先:六氢二苯并[a,g]喹嗪类化合物、其制备方法及其药物组合物和应用。中国发明专利,专利号:201010256124.8
四、主要荣誉
(1)1999年获得美国骨科研究会授予的青年研究者奖(New Investigator Recognition Award)
(2)2003年获得美国CUNY研究基金2003年度奖(PSC-CUNYresearch Foundation Research Competitive Award)
(3)2009 年获得药明康德生命化学奖
(4)2011.11入选江苏省“双创”计划
五、社会兼职
中国药理学会神经药理学会副主任委员;江苏药理学会副理事长;中国神经科学学会理事;APS,Frontier in Neuroscience编委。