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王鴻利

 

王鴻利 (Hung-Li Wang)

職稱:生理暨藥理學科教授

研究室名稱:分子神經科學研究室

最高學歷:Ph.D.

學校/國家:University of Pennsylvania, USA

分機號碼:5060

電子郵件帳號hlwns@mail.cgu.edu.tw

個人網頁網址:

研究室現有: 博士後研究員 1

博士班研究生  2

碩士班研究生 2 

專任研究助理  4

大學部專題生  1 

 

研究方向研究室特色
1. 神經系統疾病的細胞及分子病理機轉
許多神經系統疾病源自於離子通道、神經傳遞質受體及調節突觸傳遞之重要分子的基因突變或基因表現異常,因此本研究室結合分子與細胞生物學、電生理學、基因轉殖鼠及基因剔除鼠等技術探討下列神經系統疾病的致病機轉: (A)第三型脊髓小腦性運動失調症(Spinocerebellar  ataxia type 3;SCA3)及第七型脊髓小腦性運動失調症(SCA7)是第三型運動失調質(ataxin-3)或第七型運動失調質(ataxin-7)之基因突變所導致的遺傳型顯性神經病變,為了瞭解SCA3及SCA7的致病機轉,我們利用基因轉殖鼠探討突變多麩酸胺第三型運動失調質及突變第七型運動失調質引起神經元功能異常與死亡的分子機轉。(B)黑質緻密部(substantia nigra pars compacta) 的多巴胺神經元病變導致的帕金森氏症(Parkinson’s disease)是最常見的神經元性運動障礙疾病,PTEN-induced kinase 1 (PINK1)或leucine-rich repeat kinase 2 (LRRK2)的基因突變引起遺傳型帕金森氏症,我們利用帕金森氏症之基因轉殖鼠及基因剔除鼠動物研究突變PINK1或突變 LRRK2引起多巴胺神經元病變的分子機轉。(C) LGI1(leucine-rich glioma inactivated gene 1)之基因突變是引起顯性遺傳型側顳葉癲癇 (autosomal dominant lateral temporal lobe epilepsy; ADLTE)的病因,我們利用表現突變LGI1之的基因轉殖鼠引起側顳葉癲癇的分子病理機轉。
2. 痛覺生理學及病理學研究
(A) 腦部鎮痛神經迴路的電生理學研究: 由頭側無顆粒性腦島皮質(rostral agranular insular cortex; RAIC)、杏仁體中核(central amygdala nucleus; CeA)、中腦導水管周圍灰質(periaqueductal gray; PAG)及頭腹中側延腦(rostral ventromedial medulla; RVM)組成的下傳鎮痛神經迴路(descending antinociceptive neuronal circuitry)是腦部控制脊髓背角疼覺傳遞的重要構造,各項研究結果顯示包括鴉片樣胜肽(opioid peptides)、致痛素(nociceptin)與抑痛素(nocistatin)等神經胜肽(neuropeptides)可能經由調節CeA-PAG- RVM 或RAIC-PAG-RVM鎮痛神經通路的活性進而影響脊髓背角疼覺傳遞。為了更加了解這些神經傳遞質控制疼覺傳遞的生理功能,本研究室利用腦切細胞膜片鉗制記錄法探討上述神經胜肽對腦部鎮痛神經迴路的神經元之生理作用及其作用的離子及分子機轉。 (B) 慢性疼痛中引起痛覺過敏的分子機轉: 當皮下組織發炎或周圍神經病變造成慢性疼痛時,包括interleukin-1b (IL-1b)、interleukin-6 (IL-6)及tumor necrosis factor-a (TNF-a)等發炎性細胞介素(proinflammatory cytokines)與如CCL2及CX3CL1等化學激素(chemokines)在背根神經節(dorsal root ganglion)及脊髓背角(spinal dorsal horn)的表現大量增加。我們利用慢性疼痛動物模式、電生理學及分子生物學等方法探討發炎性細胞介素與化學激素改變傳送痛覺之根神經節神經元、脊髓背角神經元與腦部鎮痛神經迴路之神經元的訊息特性,進而促進痛覺傳遞及引起痛覺過敏(hyperalgesia)的分子機轉。

最近五年所發表論文:

 

Selected Publications:

  1. Weng YH, Chen CY, Lin KJ, Chen YL, Yeh TH, Hsiao IT, Chen IJ, Lu CS, Wang HL* (2016) (R1441CLRRK2 induces the degeneration of SN dopaminergic neurons and alters the expression of genes regulating neuronal survival in a transgenic mouse model. Experimental Neurology, 275, 104-115.
  2. Chou AH, Chen YL, Chiu CC, Yuan SJ, Weng YH, Yeh TH, Lin YL, Fang JM, Wang HL* (2015)T1-11 and JMF1907 ameliorate polyglutamine-expanded ataxin-3-induced neurodegeneration, transcriptional dysregulation and ataxic symptom in the SCA3 transgenic mouse. Neuropharmacology, 99, 308-317.
  3. Chiu CC, Yeh TH, Lai SC, Wu-Chou YH, Chen CH, Mochly-Rosen D, Huang YC, Chen YJ, Chen CL, Chang YM, Wang HL*, Lu CS (2015) Neuroprotective effects of aldehyde dehydrogenase 2 activation in rotenone-induced cellular and animal models of parkinsonism. Experimental Neurology, 263, 244-253.
  4. Chou AH, Chen YL, Hu SH, Chang YM, Wang HL* (2014) Polyglutamine-expanded ataxin-3 impairs long-term depression in Purkinje neurons of SCA3 transgenic mouse by inhibiting HAT and impairing histone acetylation. Brain Research, 1583, 220-229.
  5. Huang YC, Wei KC, Chang CN, Chen PY, Hsu PW, Chen CP, Lu CS, Wang HL, Gutmann DH, Yeh TH (2014) Transglutaminase 2 expression is increased as a function of malignancy grade and negatively regulates cell growth in meningioma. PLoS One. 9, e108228
  6. Chou JS, Chen CY, Chen YL, Weng YH, Yeh TH, Lu CS, Chang YM, Wang HL* (2014) (G2019S) LRRK2 causes early-phase dysfunction of SNpc dopaminergic neurons and impairment of corticostriatal long-term depression in the PD transgenic mouse. Neurobiology of Disease, 68, 190-199.
  7. Huang CY, Chen YL, Li AH, Lu JC, Wang HL* (2014) Minocycline, a microglial inhibitor, blocks spinal CCL2-induced heat hyperalgesia and augmentation of glutamatergic transmission in substantia gelatinosa neurons. Journal of Neuroinflammation. 2014, 11:7
  8. Wang HL*, Chang NC, Weng YH, Yeh TH (2013) XLID CUL4B mutants are defective in promoting TSC2 degradation and positively regulating mTOR signaling in neocortical neurons. Biochimica et Biophysica Acta, Molecular Basis of Disease, 1832, 585-593.
  9. Wang HL*, Hu SH, Chou AH, Wang SS, Weng YH, Yeh TH (2013) H1152 promotes the degradation of polyglutamine-expanded ataxin-3 or ataxin-7 independently of its ROCK-inhibiting effect and ameliorates mutant ataxin-3-induced neurodegeneration in the SCA3 transgenic mouse. Neuropharmacology, 70, 1-11.
  10. Chen CY, Weng YH, Chien KY, Lin KJ, Yeh TH, Cheng YP, Lu CS, Wang HL* (2012) (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD. Cell Death & Differentiation, 19, 1623-1633.
  11. Kao DJ, Li AH, Chen JC, Luo RS, Chen YL, Lu JC, Wang HL* (2012) CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Nav1.8 sodium channels in dorsal root ganglion neurons. Journal of Neuroinflammation, 9,189.
  12. Chao PK, Lu KT, YL, Chen JC, Wang HL, Yang YL, Cheng MY, Liao MF, Ro LS (2012) Early Systemic granulocyte-colony stimulating factor treatment attenuates neuropathic pain after peripheral nerve injury. PLoS ONE, 7:e43680.
  13. Chou AH, Chen SY, Yeh TH, Weng YH, Wang HL* (2011) HDAC inhibitor sodium butyrate reverses transcriptional downregulation and ameliorates ataxic symptoms in a transgenic mouse model of SCA3. Neurobiology of Disease, 41, 481-488.
  14. Wang HL*, Chou AH, Wu AS; Chen SY, Weng YH, Kao YC, Yeh TH, Lu CS (2011) PARK6 PINK1 mutants are defective in maintaining mitochondrial membrane potential and inhibiting ROS formation of substantia nigra dopaminergic neurons. Biochimica et Biophysica Acta, Molecular Basis of Disease, 1812, 674-684.
  15. Chou AH, Lin AC; Hong KY, Hu SH, Chen YL, Chen JY and Wang HL* (2011) p53 activation mediates polyglutamine-expanded ataxin-3 upregulation of Bax expression in cerebellar and pontine nuclei neurons. Neurochem. Int., 58, 145-152.
  16. Lee WS, Yan JY, Chiang YC, Hung TW, Wang HL, Chiou LC, Ho KI (2011) Differential pharmacological actions of methadone and buprenorphine in human embryonic kidney 293 cells coexpressing human mu-opioid and opioid receptor-like 1 receptors. Neurochem. Res., 36, 2008-2021.
  17. Lin YT, Ro LS, Wang HL Chen JC (2011) Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain: an invivo and in vitro study. Journal of Neuroinflammation, 8, 126.
  18. Wang HL*, Chou AH, Lin AC; Chen SY, Weng YH, Yeh TH (2010) Polyglutamine-expanded ataxin-7 upregulates Bax expression by activating p53 in cerebellar and inferior olivary neurons. Exp Neurol. 224, 486-494.
  19. Chen YL, Li AH, Yeh TH, Chou AH, Weng YS, Wang HL* (2010) Nocistatin excites rostral agranular insular cortex-periaqueductal gray projection neurons by enhancing transient receptor potential cation conductance via G(aq/11)-PLC-protein kinase C pathway. Neuroscience. 168, 226-239.
  20. Chou AH, Chen CY, Chen SY, Chen WJ, Chen YL, Weng YS, Wang HL* (2010) Polyglutamine-expanded ataxin-7 causes cerebellar dysfunction by inducing transcriptional dysregulation. Neurochem. Int., 56, 329-339.
  21. Chen YL, Li AH, Yeh TH, Chou AH, Wang HL* (2009) Nocistatin and nociceptin exert opposite effects on the excitability of central amygdala nucleus-periaqueductal gray projection neurons. Mol Cell Neurosci 40, 76-88.

 

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