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林達顯
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  • 職稱: 教授
  • 學歷: PhD. Chemistry, University of California, San Diego
  • 辦公室: 台北榮總致德樓B-15
  • 電話: 886-2-28712121 ext.2703
  • Email:  這個 E-mail 地址已經被防止灌水惡意程式保護,您需要啟用 Java Script 才能觀看
  • 個人網頁:http://www.mre.vghtpe.gov.tw/laboratory/Nuclear_Magnetic_Resonance/
  • 研究領域
  • Alzheimer’s disease is thought to be associated with aggregation of β-amyloid peptide (Aβ). The aggregation process of Aβ involves conformational changes, suggesting that the structural property and conformational stability play an important role in Aβ aggregation. It has been shown that genetically mutated Aβ,订 which cause early-onset familial Alzheimer’s disease (FAD), are more prone to aggregation than wild-type Aβ, suggesting that genetic mutation might alter the structural property and conformational stability of Aβ. Currently, we are investigating the effect of genetic mutation on Aβ structure. Study of the effect of Aβ structure on its aggregation behavior may help us gain more insight into Aβ aggregation mechanism from the structural point of view.
  • Human apolipoprotein E (apoE) has been known to play a key role in the transport of plasma cholesterol and lipoprotein metabolism. It is also highly associated with late-onset familial and sporadic Alzheimer’s disease (AD). ApoE has three major isoforms, apoE2, apoE3, and apoE4. The three isoforms differ from one another only by one or two amino acids, but have markedly differences in their biological functions. The lipid- and receptor-binding abilities of apoE are isoform-specific, suggesting that structural characteristics of apoE isoforms might play important roles in their functions. We are interested in the structure-functional relationship of apoE isoforms.
  • Protein phosphatase 1 (PP1) is one of the major serine/threonine eukaryotic protein phosphatases. It plays a critical role in the regulation of various cellular functions, including carbohydrate metabolism, protein synthesis, cell cycle, muscle contraction and neuronal signaling. The catalytic subunit of PP1 in cells is associated with different binding proteins to form a variety of holoenzymes. These binding proteins may target the enzyme to specific subcellular compartments in which PP1 regulates the functions of its substrates. The catalytic subunit of PP1 is specifically regulated by three protein inhibitors, inhibitor-1, DARPP-32 (dopamine and cAMP-regulated phosphoprotein of apparent Mr 32,000) and inhibitor-2. The inhibition of PP1 is regulated through phosphorylation of these protein inhibitors. Our goal is to understand the molecular mechanisms of PP1 regulation from the structural point of view.
  • 研究著作
    • Yu-Shan Lin, Hsien-Lu Huang, Wei-Ting Liu, Ta-Hsien Lin* and Hsien-Bin Huang*  Identification of the High Molecular Weight Isoform of Phostensin , 2014, Int. J. Mol. Sci., 15, 1068-1079, doi:10.3390/ijms15011068

     

    • Chen-Yuan Kao, Jun-Kun Lai, Ta-Hsien Lin, Yu-Jiun Lin, Jeng-Shiung Jan*, Steven S.-S. Wang* Examining the inhibitory actions of copolypeptides against amyloidfibrillogenesis of bovine insulin, 2013, Biochemical Engineering Journal, 78, 181-188.

     

    • Yi-Ru Chen, Hsien-bin Huang, Chi-Jen Lo, Chih-Ching Wang, Li-Kang Ho, Hsin-Tzu Liu, Ming-Shi Shiao, Ta-Hsien Lin*, Yi-Cheng Chen* Effect of Alanine Replacement of L17 and F19 on the Aggregation and Neurotoxicity of Arctic-Type Aβ40, 2013, PLOS ONE, 8, e61847.

     

    • Deli Irene, Fu-Hsing Sung, Jian-Wen Huang, Ta-Hsien Lin, Yi-chen Chen and Chia-Lin Chyan* Resonance assignments and secondary structure of calmodulin in complex with its target sequence in rat olfactory cyclic nucleotide-gated ion channel, 2013, Biomol. NMR Assign., DOI 10.1007/s12104-013-9461-y.

     

    • Deli Irene, Jian-Wen Huang, Tse-Yu Chung, Feng-Yin Li, Jason T.-C. Tzen, Ta-Hsien Lin and Chia-Lin Chyan* Binding orientation and specificity of calmodulin to rat olfactory cyclic nucleotide-gated ion channel, 2013, J. Biomol. Struct. Dyn., 31, 414-425.

     

    • Tzu-Fan Wang, Ning-Sheng Lai, Kuang-Yung Huang, Hsien-Lu Huang, Ming-Chi Lu, Yu-Shan Lin, Chun-Yu Chen, Su-Qin Liu, Ta-Hsien Lin* and Hsien-Bin Huang* Identification and Characterization of the Actin-Binding Motif of Phostensin, 2012, Int. J. Mol. Sci., 13, 15967-15982.

     

    • Chih-Ching Wang, Hsien-bin Huang, Huey-Jen Tsay, Ming-Shi Shiao, Wen-Jin Winston Wu, Yi-Chen Chen* and Ta-Hsien Lin* Characterization of Aβ40 aggregation mechanism probing by Congo red, 2012, J. Biomol. Struct. Dyn., 30, 160-169.

     

    • Yi-Ru Chen, Hsien-bin Huang, Chi-Jen Lo, Chih-Ching Wang, Chia-Li Su, Hsin-Tzu Liu, Ming-Shi Shiao, Ta-Hsien Lin* and Yi-Chen Chen* Aβ40(L17A/F19A) mutant diminishes the aggregation and neurotoxicity of Aβ40, 2011, Biochem. Biophy. Res. Commun., 405, 91-95.

     

    • H. Chou, M.F. Tam, S.-S. Lee, R.-B. Tang, T.-H. Lin, H.-Y. Tai, Y.-S. Chen, H.-D. Shen* Asp159 is a critical core amino acid of an IgE-binding and cross-reactive epitope of a dust mite allergen Der f 7, 2011, Molecular Immunology, 48, 2130-2134.

     

    • C. A. Yang, Y. H. Chen, S. C. Ke, Y. R. Chen, H. B. Huang, T. H. Lin* and Y. C. Chen* Correlation of Copper Interaction, Copper-driven Aggregation and Copper-driven H2O2 Formation with Aβ40 Conformation, 2010, Int J Alzheimers Dis 2011, 607861.

     

    • Chun-Yu Chen, Ning-Sheng Lai, Jaw-Ji Yang, Hsien-lu Huang, Wei-ChuanHung, Chin Li, Ta-Hsien Lin* and Hsien-bin Huang* FLJ23654 encodes a heart protein phosphatase 1-binding protein (Hepp1), 2010, Biochem. Biophy. Res. Commun., 391, 698-702. Impact Factor 2.406.

     

    • Yi-Choang Huang, Yi-Chen Chen, Huey-Jen Tsay, Chia-lin Chyan, Chun-Yu Chen, Hsien-bin Huang* and Ta-Hsien Lin*, The effect of PKA-Phosphorylation on the structure of inhibitor-1 studied by NMR spectroscopy, 2010, J. Biochem., 147, 273-278.

     

    • Yang, C. A., Chen, Y. H., Ke, S. C., Chen, Y. R., Huang, H. B., Lin, T. H.*, and Chen, Y. C.*, Correlation of Copper Interaction, Copper-driven Aggregation and Copper-driven H2O2 Formation with Aβ40 Conformation, (2010) Int J Alzheimers Dis 2011, 607861

     

    • Huang, Y. C., Chen, Y. C., Tsay, H. J., Chyan, C. L., Chen, C. Y., Huang, H. B.*, and Lin, T. H.*, The effect of PKA-Phosphorylation on the structure of inhibitor-1 studied by NMR spectrscopy, (2010) Journal of biochemistry 147, 273-278

     

    • Chen, C. Y., Lai, N. S., Yang, J. J., Huang, H. L., Hung, W. C., Li, C., Lin, T. H.*, and Huang, H. B.*, FLJ23654 encodes a heart protein phosphatase 1-binding protein (Hepp1), (2010) Biochemical and biophysical research communications 391, 698-702

     

    • Lai, N. S., Wang, T. F., Wang, S. L., Chen, C. Y., Yen, J. Y., Huang, H. L., Li, C., Huang, K. Y., Liu, S. Q., Lin, T. H.*, and Huang, H. B.*, Phostensin caps to the pointed end of actin filaments and modulates actin dynamics, (2009) Biochemical and biophysical research communications 387, 676-681

     

    • Liao, M. Q., Tzeng, Y. J., Chang, L. Y., Huang, H. B., Lin, T. H., Chyan, C. L., and Chen, Y. C., The correlation between neurotoxicity, aggregative ability and secondary structure studied by sequence truncated A# peptides, (2007) FEBS letters 581, 1161-1165

     

    • Kao, S. C., Chen, C. Y., Wang, S. L., Yang, J. J., Hung, W. C., Chen, Y. C., Lai, N. S., Liu, H. T., Huang, H. L., Chen, H. C., Lin, T. H.*, and Huang, H. B.*, Identification of phostensin, a PP1 F-actin cytoskeleton targeting subunit, (2007) Biochemical and biophysical research communications 356, 594-598

     

    • Huang, H. B.*, Chen, Y. C., Lee, T. T., Huang, Y. C., Liu, H. T., Liu, C. K., Tsay, H. J., and Lin, T. H.*, Structural and Biochemical Characterization of Inhibtor-1alpha, (2007) Proteins 68, 779-788

     

    • Chen, Y. R., Huang, H. B., Chyan, C. L., Shiao, M. S., Lin, T. H.*, and Chen, Y. C.*, The Effect of Abeta Conformation on the Metal Affinity and Aggregation Mechanism Studied by Circular Dichroism Spectroscopy, (2006) Journal of biochemistry 139, 733-740

     

    • Lou, B. S., Lin, T. H., and Lo, C. Z., The interactions of phenytoin and its binding site in DI-S6 segment of Na+ channel voltage-gated peptide by NMR spectroscopy and molecular modeling study , (2005) The journal of peptide research : official journal of the American Peptide Society 66, 27-38

     

    • Lin, T. H., Tsai, P. C., Liu, H. T., Chen, Y. C., Wang, L. H., Hsieh, F. K., and Huang, H. B., Characterization of the Protein Phosphatase 1-binding Motifs of Inhibitor-2 and DARPP-32 by Surface Plasmon Resonance, (2005) Journal of biochemistry 138, 697-700

     

    • Lin, T. H., Huang, H. B., Wei, H. A., Shiao, S. H., and Chen, Y. C.,  The effect of temperature and lipid on the conformational transition of gramicidin A in lipid vesicles, (2005) Biopolymers 78, 179-186

     

    • Ho, Y., Hsiao, J. C., Yang, M. H., Chung, C. S., Peng, Y. C., Lin, T. H., Chang, W., and Tzou, D. L.,  The Oligomeric Structure of Vaccinia Viral Envelope Protein A27L is Essential for Binding to Heparin and Heparan Sulfates on Cell Surfaces: A Structural and Functional Approach Using Site-specific Mutagenesis, (2005) Journal of molecular biology 349, 1060-1071

     

    • Chyan, C. L., Huang, P. C., Lin, T. H., Huang, J. W., Lin, S. S., Huang, H. B., and Chen, Y. C., Purification, crystallization and preliminary crystallographic studies of a Camodulin-OLFp molecule , (2005) Acta crystallographica. Section F, Structural biology and crystallization communications 61, 785-787

     

    • Chou, C. Y., Lin, Y. L., Huang, Y. C., Sheu, S. Y., Lin, T. H., Tsay, H. J., Chang, G. G., and Shiao, M. S., Structural Variation in Human Apolipoprotein E3 and E4: Secondary Structure, Tertiary Structure, and Size Distribution , (2005) Biophysical journal 88, 455-466

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