镇学初

发布者：金雪明发布时间：2022-07-14浏览次数：14820



姓　　名：镇学初

职称职务：特聘教授、省重点实验室主任、省双创团队领军人

电子邮箱：zhenxuechu@suda.edu.cn

办公地址：云轩楼2305


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：bat365中文官方网站，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130余篇。申请中国专利18项,已授权5项。先后主持科技部863计划子课题、国家自然科学基金杰出青年科学基金、国家自然科学基金重点项目、国家重大专项新药创制等项目。

1、近五年发表的论文（按时间倒序）

  1. Wang X, Chen S, Ni J, Cheng J, Jia J*, Zhen X*. miRNA-3473b contributes to neuroinflammation following cerebral ischemia.Cell Death Dis. 2018 Jan 9;9(1):11.

  2. Cao T,Zhen X*. Dysregulation of miRNA and its potential therapeutic application in schizophrenia. CNS Neurosci Ther. 2018 Mar 12. doi: 10.1111/cns.12840.

  3. Jia J, Cheng J, Wang C*, Zhen X*. Sigma-1 Receptor-Modulated Neuroinflammation in Neurological Diseases. Front Cell Neurosci. 2018, 12:314.

  4. Zheng J, Zhang X*, Zhen X*. Development of Adenosine A2A Receptor Antagonists for the Treatment of Parkinson's Disease: A Recent Update and Challenge. ACS Chem Neurosci. 2018 Sep 21. doi: 10.1021/acschemneuro.8b00313.

  5. Zhen X, Waddington J. Emerging and evolving concepts in the pathobiology and treatment of psychosis.CNS Neurosci Ther. 2018 Jul;24(7):583-585.

  6. Yan Q, Han C, Wang G, Waddington JL, Zheng L, Zhen X*. Activation of AMPK/mTORC1-mediated autophagy by metformin reverses Clk1 deficiency - sensitized dopaminergic neuronal death. Mol Pharmacol. 2017, 92(6):640-652.

  7. Ren Z, Yan P, Zhu L, Yang H, Zhao Y, Kirby BP, Waddington JL, Zhen X*. Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of neuroinflammation. Psychopharmacology (Berl). 2018 Jan;235(1):233-244.

  8. Zhang L, Yang H, Zhang W, Liang Z, Huang Q, Xu G, Zhen X*, Zheng LT. Clk1-regulated aerobic glycolysis is involved in glioma chemoresistance. J Neurochem. 2017, 142(4):574-588.

  9. Tian S, Wang X, Li L, Zhang X, Li Y, Zhu F, Hou T, Zhen X*. Discovery of Novel and Selective Adenosine A2A Receptor Antagonists for Treating Parkinson's Disease through Comparative Structure-Based Virtual Screening. J Chem Inf Model. 2017, 57(6):1474-1487.

  10. Zhao YF, Wang PP, Chen SS, Han CJ, Yan QT, Zheng LT, Jia J, Ren ZX, Zhen XC*. Dihydromyricetin protects against cerebral ischemia/reperfusion injury via suppressing microglia-mediated neuroinflammation and activation of ERK1/2-CREB signaling pathway. Journal of Functional Foods. 2017, 33: 76–84.

  11. O'Tuathaigh CMP, Moran PM, Zhen XC, Waddington JL. Translating advances in the molecular basis of schizophrenia into novel cognitive treatment strategies. Br J Pharmacol. 2017, 174(19):3173-3190.

  12. Gu R., Zhang F, Chen G, Han C, Liu J, Ren Z, Zhu Y, J. L. Waddington, Zheng L, Zhen X*.  Clk1 deficiency promotes neuroinflammation and subsequent dopaminergic cell death through regulation of microglial metabolic reprogramming. Brain Behav Immun. 2017, 60: 206-219.

  13. Liu T, Yang X, Zheng L, Wang G, Zhen X*. Activation of Nur77 in microglia attenuates proinflammatory mediators production and protects dopaminergic neurons from inflammation-induced cell death. J Neurochem. 2017, 140(4): 589-604.

  14. Wang J, Sun P, Ren Z, H. Y. Meltzer, Zhen X*. GSK-3beta Interacts with Dopamine D1 Receptor to Regulate Receptor Function: Implication for Prefrontal Cortical D1 Receptor Dysfunction in Schizophrenia. CNS Neurosci Ther. 2017, 23(2): 174-187.

  15. Wu J, Zhao R, Guo L, Zhen X*. Morphine-induced inhibition of Ca2+ -dependent d-serine release from astrocytes suppresses excitability of GABAergic neurons in the nucleus accumbens. Addict Biol. 2017, 22(5):1289-1303

  16. Guo L, Guo Z, Luo X, Liang R, Yang S, Ren H, Wang G, Zhen X*. Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory. Neurosci Lett. 2016, 635: 44-50.

  17. Li W, Zhang L, Xu L, Yuan C, Du P, Chen J, Zhen X*, Fu W. Functional reversal of (-)-Stepholidine analogues by replacement of benzazepine substructure using the ring-expansion strategy. Chem Biol Drug Des. 2016, 88(4): 599-607.

  18. Ren Z, Zhao Y, Cao T, Zhen X*. Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson's disease by suppressing glycogen synthase kinase-3 beta activity. Acta Pharmacol Sin. 2016, 37(10): 1315-1324.

  19. Wang Y, Guo L, Jiang H, Zheng L, Zhang A, Zhen X*. Allosteric Modulation of Sigma-1 Receptors Elicits Rapid Antidepressant Activity. CNS Neurosci Ther. 2016, 22(5): 368-377.

  20. Yang Z, Li L, Zheng J, Ma H, Tian S, Li J, Zhang H, Zhen X*, Zhang X. Identification of a New Series of Potent Adenosine A2A Receptor Antagonists Based on 4-Amino-5-carbonitrile Pyrimidine Template for the Treatment of Parkinson's Disease. ACS Chem Neurosci. 2016, 7(11): 1575-1584.

  21. Zhang Y, Gu R, Jia J, Hou T, Zheng L, Zhen X*. Inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity suppresses microglia-mediated inflammatory responses. Clin Exp Pharmacol Physiol. 2016, 43(11): 1134-1144.

  22. Zhao R, Chen J, Ren Z, Shen H, Zhen X*. GSK-3beta inhibitors reverse cocaine-induced synaptic transmission dysfunction in the nucleus accumbens. Synapse. 2016, 70(11): 461-470.

  23. Dong X, Zhen X*. Glial pathology in bipolar disorder: potential therapeutic implications. CNS Neurosci Ther. 2015, 21(5): 393-397.

  24. Gan P, Zhang L, Chen Y, Zhang Y, Zhang F, Zhou X, Zhang X, Gao B, Zhen X, Zhang J, Zheng L. Anti-inflammatory effects of glaucocalyxin B in microglia cells. J Pharmacol Sci. 2015, 128(1): 35-46.

  25. Guo L, Chen Y, Zhao R, Wang G, Friedman E, Zhang A, Zhen X*. Allosteric modulation of sigma-1 receptors elicits anti-seizure activities. Br J Pharmacol. 2015, 172(16): 4052-4065.

  26. Guo L, Zhen X*. Sigma-2 receptor ligands: neurobiological effects. Curr Med Chem. 2015, 22(8): 989-1003.

  27. Jia J, Cheng J, Ni j, Zhen X*. Neuropharmacological Actions of Metformin in Stroke. Curr Neuropharmacol. 2015, 13(3): 389-394.

  28. Lian P, Li L, Geng C, Zhen X*, Fu W. Higher-Affinity Agonists of 5-HT1AR Discovered through Tuning the Binding-Site Flexibility. J Chem Inf Model. 2015, 55(8): 1616-1627.

  29. Liu C, Fang X, Wu Q, Jin G, Zhen X*. Prefrontal cortex gates acute morphine action on dopamine neurons in the ventral tegmental area. Neuropharmacology. 2015, 95: 299-308.

  30. Ni J, Wang X, Chen S, Liu H, Wang Y, Xu X, Cheng J, Jia J, Zhen X*. MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation. Brain Behav Immun. 2015, 49: 75-85.

  31. Wu Z, Li L, Zheng L, Xu Z, Guo L, Zhen X*. Allosteric modulation of sigma-1 receptors by SKF83959 inhibits microglia-mediated inflammation. J Neurochem. 2015, 134(5): 904-914.

  32. Zhang Y, Xu L, Zhang Z, Zhang Z, Zheng L, Li D, Li Y, Liu F, Yu K, Hou T, Zhen X*. Structure-Activity Relationships and Anti-inflammatory Activities of N-Carbamothioylformamide Analogues as MIF Tautomerase Inhibitors. J Chem Inf Model. 2015, 55(9): 1994-2004.

  33. Jin Q, Cheng J, Liu Y, Wu J, Wang X, Wei S, Zhou X, Qin Z, Jia J, Zhen X*. "Improvement of functional recovery by chronic metformin treatment is associated with enhanced alternative activation of microglia/macrophages and increased angiogenesis and neurogenesis following experimental stroke. Brain Behav Immun. 2014, 40: 131-142.

  34. Li Z, Huang J, Sun H, Zhou S, Guo L, Zhou Y, Zhen X*, Liu H. Design, synthesis and evaluation of benzo[a]thieno[3,2-g]quinolizines as novel l-SPD derivatives possessing dopamine D1, D2 and serotonin 5-HT1A multiple action profiles. Bioorg Med Chem. 2014, 22(21): 5838-5846. (

  35. Mu Y, Ren Z, Jia J, Gao B, Zheng L, Wang G, Friedman E, Zhen X*. Inhibition of phosphodiesterase10A attenuates morphine-induced conditioned place preference. Mol Brain. 2014, 7: 70.

  36. Tao L, Zhang F, Hao L, Wu J, Jia J, Liu JY, Zheng LT, Zhen X*. 1-O-tigloyl-1-O-deacetyl-nimbolinin B inhibits LPS-stimulated inflammatory responses by suppressing NF-kappaB and JNK activation in microglia cells. J Pharmacol Sci. 2014, 125(4): 364-374.

  37. Xu L, Zhang Y, Zheng L, Qiao C, Li Y, Li D, Zhen X* Hou T. Discovery of novel inhibitors targeting the macrophage migration inhibitory factor via structure-based virtual screening and bioassays. J Med Chem. 2014, 57(9): 3737-3745.

  38. Yang Y, Zheng L, Shi J, Gao B, Chen Y, Yang H, Chen H, Li Y, Zhen X*. Synthesis of 5alpha-cholestan-6-one derivatives and their inhibitory activities of NO production in activated microglia: discovery of a novel neuroinflammation inhibitor. Bioorg Med Chem Lett. 2014, 24(4): 1222-1227.

  39. Yang Z, Li X, Ma H, Zheng J, Zhen X*, Zhang X. Replacement of amide with bioisosteres led to a new series of potent adenosine A2A receptor antagonists. Bioorg Med Chem Lett. 2014, 24(1): 152-155.

  40. Zhang J, Huang J, Song Z, Guo L, Cai W, Wang Y, Zhen X*, Zhang A. Structural manipulation on the catecholic fragment of dopamine D(1) receptor agonist 1-phenyl-N-methyl-benzazepines. Eur J Med Chem. 2014, 85: 16-26.

  41. Zhao R, Lu W, Fang X, Guo L, Yang Z, Ye N, Zhao J, Liu Z, Jia J, Zheng L, Zhao B, Zhang A, Zhen X*. (6aR)-11-amino-N-propyl-noraporphine, a new dopamine D2 and serotonin 5-HT1A dual agonist, elicits potent antiparkinsonian action and attenuates levodopa-induced dyskinesia in a 6-OHDA-lesioned rat model of Parkinson's disease. Pharmacol Biochem Behav. 2014, 124: 204-210.

  42. Zhou S, Chu H, Jin G, Cui J, Zhen X*. Effects of SKF83959 on the excitability of hippocampal CA1 pyramidal neurons: a modeling study. Acta Pharmacol Sin. 2014, 35(6): 738-751.

  43. Zhou X, Gan P, Hao L, Tao L, Jia J, Gao B, Liu J, Zheng L, Zhen X*. Antiinflammatory effects of orientin-2"-O-galactopyranoside on lipopolysaccharide-stimulated microglia. Biol Pharm Bull. 2014, 37(8): 1282-1294.

  44. Zheng J, Yang Z, Li X, Li L, Ma H, Wang M, Zhang H, Zhen X, Zhen X*. Optimization of 6 Heterocyclic-2-(1H pyrazol-1-yl) N (pyridin-2-yl)pyrimidin-4-amine as Potent Adenosine A2A Receptor Antagonists for the Treatment of Parkinson’s Disease. ACS Chem Neurosci. 2014, 5(8):674-82.

  45. Tian S, Sun H, Pan P, Li D, Zhen X, Li Y, Hou T. Assessing an ensemble docking-based virtual screening strategy for kinase targets by considering protein flexibility. J Chem Inf Model. 2014, 54(10): 2664-2679.


2、课题 

在研项目:

  1. 国家自然科学基金面上项目，别构调节Sigma-1受体抗抑郁作用及其机制研究（2018-2021），81773702，63.5万元，主持人。

  2. 江苏省重大神经精神疾病研究重点实验室（2013-），600万元，主持人。

  3. 江苏省优势学科3期建设项目药学（2018-2022），2360万元，主持人。

已结题项目:

  1. 国家自然科学基金重点项目，精神分裂症前额叶功能紊乱的机制（2012-2016），81130023，260万元，主持人。

  2. 国家自然科学基金面上项目，前额叶皮层锥体神经元顶树突震荡形式编码的性质，机制及其与药物成瘾的关系研究（2014-2017），81373382，100万元，主持人。

  3. 国家自然科学基金杰出青年基金项目，神经精神药理学研究（2008-2012），30825042，200万元，主持人。

  4. 国家重大专项新药创制项目，THPB-d抗精神分裂症作用的临床前研究项目（2009-2011），2009ZX09102-023，300万元，主持人。

  5. 科技部863项目子课题，磷脂肌醇(PI)-偶联的新型多巴胺受体基因及功能研究（2007-2011），2007AA02Z163，280万元，子课题负责人。

  6. 科技部973计划子课题，阿片类物质精神依赖的神经生物学机制（2008-2013），2009CB52200，课题骨干。

  7. 科技部973计划子课题，胶质细胞与神经损伤和修复（2010-2015），2011CB5C4403，课题骨干。


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。

（2）《高等药理学》，科技出版社，主编：丁键、镇学初，2013。


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年入选江苏省双创人才、苏州市工业园区科技领军人才

（5）2014年入选江苏省双创团队（团队领军人才）


五、社会兼职

中国神经科学学会理事；

江苏药理学会副理事长；

APS、Frontier in Neuroscience编委。



Baidu
sogou