神经精神药理研究室(镇学初 教授)

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镇学初,苏州大学药学院院长、特聘教授,博士生导师。

镇学初教授1996年获瑞士日内瓦大学博士学位,同年起在宾西法尼亚州立大学药理系进行博士后研究,2004年于纽约城市大学药理系任职副教授。2006年进入中国科学院上海药物研究所,担任研究员、神经递质课题组组长。2010年5月加入苏州大学药学院,任院长、教授。是中科院“百人计划”入选者(2006),国家自然科学基金杰出青年基金获得者(2008),江苏省“双创人才”(2011),江苏省“双创团队”(领军人才,2014),江苏省重大神经精神疾病诊疗技术研究重点实验室主任(2013)。

镇学初教授主要从事精神神经药理研究及相关药物研发。迄今发表SCI论文120余篇,申请中国专利18项,已获授权4项,合作主编学术专著《脑内多巴胺》、教材《高等药理学》。担任多个国内、国际刊物的编委。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等项目,作为骨干先后参加多个973项目。

Email: zhenxuechu@suda.edu.cn

 

主要研究方向:

(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。

 

近五年承担的科研项目:

(1) 国家自然科学基金重点项目(81130023):精神分裂症前额叶功能紊乱的机制,2011-2016,260万,结题。

(2) 国家自然科学基金面上项目(81373382):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,2014-2017,100万,在研。

 (1) 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. 2016, 60: 206-219. 

(2) 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. 2016, 140(4): 589-604.

(3) 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. 2016, 23(2): 174-187. 

(4) 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.

(5) 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. 

(6) 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. 

(7) 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. 

(8) 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. 2016, Addict Biol. doi: 10.1111/adb.12417.

(9) 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. 

(10) 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. 

(11) 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. 

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

(13) 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. 

(14) 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. 

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

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

(17) 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. 

(18) 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. 

(19) 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.

(20) 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. 

(21) 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. 

(22) 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. 

(23) 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. 

(24) 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. 

(25) 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. 

(26) 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. 

(27) 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. 

(28) 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. 

(29) 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. 

(30) 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. 

(31) 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.

(32) 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. 

(33) Du P, Xu L, Huang J, Yu K, Zhao R, Gao B, Jiang H, Zhao W, Zhen X*, Fu W. Design, synthesis, and evaluation of indolebutylamines as a novel class of selective dopamine D3 receptor ligands. Chem Biol Drug Des. 2013, 82(3): 326-335. 

(34) Fang X, Guo L, Jia J, Jin G, Zhao B, Zheng YY, Li J, Zhang A, Zhen X*. SKF83959 is a novel triple reuptake inhibitor that elicits anti-depressant activity. Acta Pharmacol Sin. 2013, 34(9): 1149-1155. 

(35) 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): 577-586.

(36) Sun H, Zhu L, Yang H, Qian W, Guo L, Zhou S, Gao B, Li Z, Zhou Y, Jiang H, Chen K, Zhen X*, Liu H. Asymmetric total synthesis and identification of tetrahydroprotoberberine derivatives as new antipsychotic agents possessing a dopamine D(1), D(2) and serotonin 5-HT(1A) multi-action profile. Bioorg Med Chem. 2013, 21(4): 856-868. 

(37) Xu L, Zhou S, Yu K, Gao B, Jiang H, Zhen X*, Fu W. Molecular modeling of the 3D structure of 5-HT(1A)R: discovery of novel 5-HT(1A)R agonists via dynamic pharmacophore-based virtual screening. J Chem Inf Model. 2013, 53(12): 3202-3211. 

(38) Liu C, Gao M, Jin GZ, Zhen X*. GABA neurons in the ventral tegmental area responding to peripheral sensory input. PLoS One. 2012, 7(12): e51507.

(39) 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(1) receptor. Bioorg Med Chem. 2012, 20(15): 4862-4871. 

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贾佳,苏州大学药学院副教授,研究方向是脑血管病损伤及修复机制研究。

Email: jiajia@suda.edu.cn

近五年承担的科研项目:

(1) 国家自然科学青年基金 81100918):巨噬细胞选择性活化对缺血性卒中后神经再生的影响,结题。

(2) 国家自然科学基金面上项目 81371278):硫化氢诱导小胶质细胞M2极化促进脑缺血后血管新生的机制研究,在研。

(3) 国家自然科学基金面上项目(81571124):硫化氢氧化代谢促进脑出血后血肿清除的新机制,在研。

近五年发表论文:

(1) Liu H, Wang Y, Xiao Y, Hua Z, Cheng J*, Jia J*. Hydrogen Sulfide Attenuates Tissue Plasminogen Activator-Induced Cerebral Hemorrhage Following Experimental Stroke. Transl Stroke Res. 2016 Jun;7(3):209-19.

(2) Chen Y, Zhang L, Ni J, Wang X, Cheng J, Li Y, Zhen X, Cao T*, Jia J*. LLDT-8 protects against cerebral ischemia/reperfusion injury by suppressing post-stroke inflammation. J Pharmacol Sci. 2016 Jun;131(2):131-7.

(3) Ni J, Wang X, Xu X , Liu H, Wang Y, Cheng J, Jia J*, Zhen X*. MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation. Brain, Behavior, and Immunity. 2015; 49:75-85.

(4) Liu Y, Wang W, Li Y, Xiao Y, Cheng J, Jia J*. The 5-Lipoxygenase Inhibitor Zileuton Confers Neuroprotection against Glutamate Oxidative Damage by Inhibiting Ferroptosis. Biol Pharm Bull. 2015; 38(8):1234-9.

(5) Jia J*, Cheng J, Ni J, Zhen X*. Neuropharmacological Actions of Metformin in Stroke. Curr Neuropharmacol. 2015;13(3):389-94.

(6) 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 Aug;40:131-42.

(7) Zhou X, Cao Y, Ao G, Hu L, Liu H, Wu J, Wang X, Jin M, Zheng S, Zhen X, Alkayed NJ, Jia J*, Cheng J*. CaMKKβ-Dependent Activation of AMP-Activated Protein Kinase Is Critical to Suppressive Effects of Hydrogen Sulfide on Neuroinflammation.Antioxid Redox Signal. 2014 Oct 20;21(12):1741-58.

(8) Jia J, Xiao Y, Wang W, Qing L, Xu Y, Song H, Zhen X, Ao G, Alkayed NJ, Cheng J. Differential mechanisms underlying neuroprotection of hydrogen sulfide donors against oxidative stress. NEUROCHEM INT. 2013 Jun;62(8):1072-8.

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郑龙太,苏州大学药学院副教授,研究方向为神经胶质细胞(microgliaastrocytes)激活调控的机制及其在神经退行性疾病中的作用。目前作为主持人负责一项国家自然科学基金,肿瘤微环境中MFG-E8对神经胶质瘤发展的作用及其机制研究(81372688

Email: zhenglongtai@suda.edu.cn

 

近五年发表论文:

(1) Gu R, Zhang F, Chen G, Han C, Liu J, Ren Z, Zhu Y, Waddington JL, Zheng LT*, Zhen X*.Clk1 deficiency promotes neuroinflammation and subsequent dopaminergic cell death through regulation of microglial metabolic reprogramming. Brain Behav Immun. 2016, 60: 206-219.

(2) Zhang Y, Gu R, Jia J, Hou T, Zheng LT*, 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. 

(3) Chen H, Han C, Wu J, Liu X, Zhan Y, Chen J, Chen Y, Gu R, Zhang L, Chen S, Jia J, Zhen X*, Zheng LT*, Jiang B. Accessible Method for the Development of Novel Sterol Analogues with Dipeptide-like Side Chains That Act as Neuroinflammation Inhibitors. ACS Chem Neurosci. 2016, 7(3):305-15.

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

(5) Liu TY, Yang XY, Zheng LT, Wang GH, Zhen XC. Activation of Nur77 in microglia attenuates proinflammatory mediators production and protects dopaminergic neurons from inflammation-induced cell death. J Neurochem. 2016, 140(4): 589-604.

(6) Wang Y, Guo L, Jiang HF, Zheng LT, Zhang A, Zhen XC. Allosteric Modulation of Sigma-1 Receptors Elicits Rapid Antidepressant Activity. CNS Neurosci Ther2016, 22(5):368-77.

(7) Xu Z, Wu J, Zheng J, Ma H, Zhang H, Zhen X, Zheng LT*, Zhang X*. Design, synthesis and evaluation of a series of non-steroidal anti-inflammatory drug conjugates as novel neuroinflammatory inhibitors. Int Immunopharmacol. 2015, 25(2):528-37.

(8) Wu J, Du J, Gu R, Zhang L, Zhen X, Li Y, Chen H, Jiang B*, Zheng LT*. Inhibition of neuroinflammation by synthetic androstene derivatives incorporating amino acid methyl esters on activated BV-2 microglia. ChemMedChem. 2015.10, 610-616. 

(9) Wu Z, Li L, Zheng LT, Xu Z, Guo L, Zhen X. Allosteric modulation of sigma-1 receptors by SKF83959 inhibits microglia-mediated inflammation. J Neurochem. 2015, 134(5):904-14.

(10) Zhou X, Gan P, Hao L, Tao L, Jia J, Gao B, Liu JY, Zheng LT*, Zhen X*. Antiinflammatory effects of orientin-2"-O-galactopyranoside on lipopolysaccharide-stimulated microglia. Biol Pharm Bull. 2014;37(8):1282-94.

(11)Xu L, Zhang Y, Zheng LT, 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):3737-45.

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孙晓辉,苏州大学药学院副教授。研究方向为离子通道在神经退行性疾病中的作用机制。目前作为主持人负责一项国家自然科学基金项目(31400924)

Email: sunxiaohui@suda.edu.cn

 

近五年发表论文:

(1) Sun X#, Zakharian E. Regulation of the temperature-dependent activation of Transient Receptor Potential Vanilloid 1 by phospholipids in planar lipid bilayers. Journal of Biological Chemistry. 2015, 290(8):4741-7

(2) Sun X#, Shi J, Delaloye K, Yang X, Yang H, Zhang G, Cui J. The interface between membrane-spanning and cytosolic domains in Ca2+-dependent K+ channels is involved in β subunit modulation of gating.Journal of Neuroscience. 2013, 33(27): 11253-11261

(3) Sun X#, Zaydman M. A., Cui J. Regulation of voltage-activated K+ channel gating by transmembrane β subunits. Frontiers in Pharmacology. 2012, 3:63  

 

课题组其他工作人员

 

                                             

高博,博士,讲师                   陈皎皎,硕士,实验员

 

                                                                                                                   

杨慧翠,硕士,实验员                   赵昕,硕士,行政秘书

 

 

课题组联系方式

联系人:赵昕

Email: joeyzhao@suda.edu.cn

电话:0512-65881160

地址:江苏省苏州市工业园区仁爱路199号苏州大学2期云轩楼

邮编:215123