高閬仙教授

E-mail
lskao@ym.edu.tw
個人網頁:
聯絡電話:
02-28267000#6252


 

學經歷:

  學歷    
  美國麻州州立大學生化博士  
  國立臺灣大學農業化學碩士 
  國立臺灣大學農業化學學士 
現職    
    國立陽明大學生命科學系暨基因體科學
      研究所教授
    國立陽明大學副校長
    國立陽明大學教務長
    國立陽明大學腦科學研究中心主任
經歷
    國立陽明大學生命科學院院長
    國立陽明大學生命科學系教授兼系主任 
    中央研究院生物醫學科學研究所研究員



研究領域:

 
分子細胞神經生物學、細胞內鈣離子調控與神經傳導物質分泌機制、神經退化性疾病病理機制

One of the important routes to transmit signals between cells in multicellular organisms is by exocytosis which allows the release of neurotransmitters and hormones. My laboratory has focused on the regulation of Ca2+-dependent exocytosis. By using electrochemical method and Ca2+ measurements, we have characterized the Ca2+ signaling pathways and secretions in mouse adrenal medullary chromaffin cells to provide knowledge for future studies on Ca2+ regulations and molecular mechanisms of Ca2+-dependent secretion using PC12 cells and mouse chromaffin cells as a model system.
We also study the role of Rab3A in exocytosis, especially in priming steps, and the possible molecular interactions among Rab3A, Munc13-1 and Munc18-1 by using fluorescence proteins combined with total internal reflection fluorescence microscope (TIRFM). Our results show that Rab3A involves in Munc13-1 and RIM interaction and is dissociated from vesicle membrane by interacting with Munc18-1 to regulate exocytosis.
Among the various Ca2+ pathways, we have focused on the Na+/Ca2+ exchanger (NCX) on the plasma membrane, which has been demonstrated as the predominant mechanism for exporting excess intracellular Ca2+ in excitable cells, such as cardiac muscle cells and neuronal cells. We have found that sarcomeric mitochondrial creatine kinase (sMiCK) and muscle type cytosolic isozyme of creatine kinase (CKM) are able to interact with NCX1. This interaction may be important in the recovery of NCX1 activity that lost under an energy-compromised state.
Another line of research in my laboratory is to study the mechanism that underlies the progressive degeneration of the dopaminergic neurons in Parkinson's disease. We have indentified an interaction between dopamine (DA) and Zn2+ that synergistically induces cell death. When PC12 cells were pretreated with Zn2+ before DA treatment, DA and Zn2+ synergistically increased cell death. There is a similar synergistic effect when DA and Zn2+ were co-infused into the striatum, resulting in striatal DA content depletion in vivo. Thus, both DA oxidation and Zn2+ are possibly linked to the degeneration of DA neurons. We are currently trying to elucidate the mechanism involved in the DA and Zn2+ induced death of DA neurons.

實驗室成員

吳珮君 博士後研究員
黃建彰 博士後研究員
蘇琬淇 碩士級助理
楊添鈞 博士班
吳學甫 碩士班
劉俊麟 碩士班
宋欣瑜 碩士班

代表著作

(2014) Tsai PC, Huang YH, Guo YC, Wu HT, Lin KP, Tsai YS, Liao YC, Liu YT, Liu TT, Kao LS (高閬仙), Yet SF, Fann MJ, Soong BW, Lee YC. A novel TFG mutation causes Charcot-Marie-Tooth disease type 2 and impairs TFG function. Neurology. 2014; 83(10):903-12.

(2014) Wang CH, Chen YF, Wu CY, Wu PC, Huang YL, Kao CH, Lin CH, Kao LS(高閬仙), Tsai TF, Wei YH. Cisd2 modulates the differentiation and functioning of adipocytes by regulating intracellular Ca2+ homeostasis. Hum Mol Genet.2014; 23:4770–4785.

(2014) Li PC, Yang YC, Hwang GY, Kao LS(高閬仙), Lin CY. Inhibition of Reverse-Mode Sodium-Calcium Exchanger Activity and Apoptosis by Levosimendan in Human Cardiomyocyte Progenitor Cell-Derived Cardiomyocytes after Anoxia and Reoxygenation. 2014; DOI: 10.1371/journal.pone.0085909

(2013) Soong BW, Huang YH, Tsai PC, Huang CC, Pan HC, Lu YC, Chien HJ, Liu TT, Chang MH, Lin KP, Tu PH, Kao LS (高閬仙), Lee YC. Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease. Am. J. Human Genet. 2013; 92: 422-430.

(2011) Huang CC, Yang DM, Lin CC, Kao LS (高閬仙). Involvement of Rab3A in vesicle priming during exocytosis: interaction with Munc13-1 and Munc18-1. Traffic 2011; 12:1356–1370.

(2011) Peng JY, Lin CC, Chen YJ, Kao LS (高閬仙), Liu YC, Chou CC, Huang YH, Chang FR, Wu YC, Tsai YS, Hsu CN. Automatic morphological subtyping reveals new roles of caspases in mitochondrial dynamics. PLoS Comput. Biol. 2011; 7:e1002212.

(2010) Wu PC, Fann MJ, Kao LS (高閬仙). Characterization of Ca2+ Signaling Pathways in Mouse Adrenal Medullary Chromaffin Cells. J. of Neurochem. 2010; 112(5):1210-1222.
(2010) Yang YC, Fann MJ, Chang WH, Tai LH, Jiang JH, Kao LS (高閬仙). Regulation of sodium-calcium exchanger activity by creatine kinase under energy-compromised conditions. Journal of Biological Chemistry. 2010; 285(36):28275-28285.

(2010) Li YC, Chen BM, Wu PC, Cheng TL, Kao LS (高閬仙), Tao MH, Lieber A, Roffler, S.R. Cutting Edge: mechanical forces acting on T cells immobilized via the TCR complex can trigger TCR signaling. J. Immunol. 2010; 184, 5959-5963.

(2009) Ku TC, Kao LS (高閬仙), Lin CC, Tsai YS. Morphological filter improve the efficiency of automated tracking of secretory vesicles with various dynamic properties. Microsc. Res. Tech. 2009; 72, 639-649.