國立中正大學 生命科學系 | 分子生物研究所 | 生物醫學研究所 專任師資

  • 張德卿
  • 蕭光明
  • 黃憲斌
  • 曾銘仁
  • 陳浩仁
  • 黃敏郎
  • 蕭淑惠
  • 江明格
  • 呂昱瑋
  • 李沁
  • 戴建國
  • 吳淑芬
  • 周正中
  • 陳永恩
  • 李政怡

  • 黃憲斌 Hsien-Bin Huang

    168, University Road, Min-Hsiung Chia-Yi Taiwan, R. O. C.
    TEL: (05)2720411 ext53200 (office), 53201(lab)
    FAX: (05)2722871
    Email: biohbh@ccu.edu.tw

    尚無動物房樓層平面圖

    • Education

      National Taiwan Normal University B.S. 1979-1984 Chemistry
      National Taiwan University M.S. 1984-1986 Biochemistry
      Cornell University Ph.D. 1987-1992 Biochemistry

    • Current Title

      Professor, Department of Life Science/Institute of Molecular Biology National Chung Cheng University

    • Employment

      Chairman, Department of Life Science, National Chung Cheng University, Aug. 2003-2005.
      Professor, Department of Life Science, National Chung Cheng University, Aug. 2008-present
      Associate Professor, Institute of Molecular Biology, National Chung Cheng University, Aug. 2000-2008.
      Associate Professor, Division of Biochemistry, Tzu Chi University, Aug. 1995- July 2000.
      Postdoctor, Lab. of Molecular and Cellular Neuroscience, The Rockefeller University
      (Advisor: Paul Greengard, The Noble Prize Laureate in 2000 for medicine and physiology), Jan. 1992-July 1995.

    • 研究領域

      Protein Neuroscience, Enzymology, Protein Chemistry.

      My research is concerned with the study of proteins, especially those involved in neuronal functions. The research involved isolation of proteins, determination of their structures and properties, cloning, and expression. The research is basic in nature, but significant relationships between this research and human disease. The research projects include two parts. First is focused on the interactions between the protein phosphatase-1 (PP1) and its regulatory proteins, which play a key role in dopaminergic signal transduction of the brain. My laboratory has identified the mechanism of PP1 regulated by one of its inhibitors, inhibitor-2. Recent studies have led to the elucidation of the first secondary structure of inhibitor-2 by NMR. Our final goals are to better understand the molecular mechanism in regulation of PP1, which may result in the design of drugs capable of mimicking or antagonizing the action of PP1, and the role of PP1 in regulation of neuronal functions. Purification and characterization of the novel PP1-binding proteins will be also included. A second area of research created recently concerns the mechanism in prevention of Ab polymerization and the structural differences of apoE isoforms, both of which are highly associated with the pathogenesis of the Alzheimer's disease (AD). Recently, we have planed to design the photo-sensitive peptides that can block the Ab polymerization. Our aim is to use NMR to elucidate 3-dimensional structure of Ab:peptide complex, providing the targets for design of therapeutic drugs in preventing the development of AD. Three common alleles of human apoE, e2, e3 and e4, are found, differing by a single amino acid substitution in residue-112 and –158 and showing the remarkable differences in their biochemistry, and cellular metabolism and biological functions. In this project, we focus on the structural studies of apoE isoforms by using NMR (collaborated with Dr. Ta-Hsien Lin, at VGH, Taipei). Our goals are to understand the relationship between protein structure and function.

    • Major awards and honors

      Research Award (甲等獎) (1997, 1999, National Science Council)
      Outstanding Research Award (2005, National Chung Cheng University)
      中正大學教師優良教學獎 (2007)

      • ^ back

    • Publication

      Book Chapter

      • Shiraishi M, Chan MWY and Huang THM. Microarray analysis of DNA methylation targets identified by Methyl-CpG binding protein. Chapter 6, in Esteller M, eds., DNA Methylation: Approaches and Applications. CRC Press, Florida. 2004.

      Journal Paper

      • Chu, S.T., Yu, C.Y., Huang, H.B. and Chen, Y.H. (1990) Heterogeneous forms of glucose-6-phosphate dehydrogenase in human erythrocytes. J. Chinese Biochem. Soc. 18, No. 1, 1-9.
      • Rose, J., Breslow, E., Huang, H.B. and Wang, B.C. (1991) Crystallographic analysis of the neurophysin-oxytocin complex. J. Mol. Biol. 221, 43-45.
      • Huang, H. B. and Breslow, E. (1992) Identification of the unstable neurophysin disulfide and location to the hormone-binding site: relationship to folding-unfolding pathway. J. Biol. Chem. 267, 6750-6756.
      • Breslow, E., Mishra, P.K., Huang, H.B. and Bothner-by, A. (1992) Interchanging conformers of bovine neurophysin I in the unliganded dimer state. Biochemistry 31, 11397-11404.
      • Huang, H.B., Laborde, T. and Breslow, E. (1993) Modulation of allosteric interactions in neurophysin induced by succinylation of ser-56 or cleavage of residues. Biochemistry 31, 10743-10749.
      • Huang, H.B., Wellner, D., Naude, R., Oelofsen, W., Oosthuizen, M.M.J. and Breslow, E. (1994) Amino acid sequence and properties of vasopressin-associated elephant neurophysin. Int. J. Peptide Protein Res. 44, 270-277.
      • Desdouits, F., Cheetham, J.J., Huang, H. B., Kwon, Y. G., da Cruz e Silva, E.F., Denefle, P., Ehrlich, M.E., Nairn, A.C., Greengard, P. and Girault, J.A. (1995) Mechanism of inhibition of protein phosphatase 1 by DARPP-32: studies with recombinant DARPP-32 and Synthetic peptides. Biochem. Biophys. Res. Commun. 206, 652-658.
      • Goldberg, J., Huang, H.B., Kwon, Y.G., Greengard, P., Nairn, A.C. and Kuriyan, J. (1995) Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature 376, 745-753.
      • Huang, H.B., Horiuchi, A., Goldberg, J., Greengard, P. and Nairn, A.C. (1997) Site-directed mutagenesis of amino acid residues of protein phosphatase-1 involved in catalysis and inhibitor binding. Proc. Natl. Acad. Sci. USA 94, 3540-3535.
      • Kwon, Y.G., Huang, H.B., Desdouits, F., Girault, J.A., Greengard, P. and Nairn, A.C. (1997) Characterization of the interaction between protein phosphatase-1 and DARPP-32: DARPP-32 peptide antagonize the interaction of protein phosphatase-1 with binding proteins. Proc. Natl. Acad. Sci. USA 94, 3536-3541.
      • Lin S.R., Huang, H.B., Wu, B.N. and Chang, L.S. (1998) Characterization and cloning of long neurotoxin homolog from naja naja atra. Biochem. Mol. Biol. Int. 46, 1211-1217.
      • Aggen, J.B., Humphrey, J.M., Gauss, C.M., Huang, H.B., Nairn, A.C. and Chamberlin, R. (1999) The design, synthesis, and biolobical evaluation of analogs of the serine-threonine protein phosphatase 1 and 2A selective inhibitor microcystin LA: rational modifications imparting PP-1 selectivity. Bioorg. Med. Chem 7, 543-564.
      • Hunag, H.B.*, Horiuchi, A., Watanabe, T., Shih, S.R., Tsay, H.J., Li., H.C., Greengard, P. and Nairn, A.C*. (1999) Characterization of the inhibition of protein phosphatase-1 by DARPP-32 and inhibitor-2. J. Biol. Chem 274, 7870-7878.
      • Chang,L.S., Lin, S.K., Huang, H.B. and Hsiao, H.S.M. (1999) Genetic organization of alpha-bungarotoxin from Bungarus multicinctus (Taiwan banded krait): Evidence showing the production of alpha-bungarotoxin isotoxins is not derived from edited mRNA. Nucleic Acids Research 27, 3970-3975.
      • Chang, L.S., Huang, H.B., and Lin, S.R. (2000) The multiplicity of cardiotoxins from Naja naja atra (Taiwan cobra) venom. Toxicon 38, 1065-1076.
      • Connor, J.H., Frederick, D., Huang, H.B., Yang, J., Helps, N.R., DePaoli-Roach, A., Cohen, P.T.W., Tatchell, K., Nairn, A.C. and Shenolikar, S. (2000) Cellular Mechanism Regulating Protein Phosphatase-1: A key Functional Interaction between Inhibitor-2 and the PP1 Catalytic Subunit. J. Biol. Chem. 275, 18670-18675.
      • Chang, L. S., Lin, S. R., Hu, W. P., Wu, B. N., and Huang, H. B. (2000) Structure-function studies on Taiwan cobra long neurotoxin homolog. Biochem. Biophys. Acta 1480, 293-301.
      • Huang, H. B., Chen, Yi-chen, Tsai, Li-huang, Wang, Hui-chun, Lin, Fang-min, Shiao, Ming-shi, and Lin, Ta-hsien Lin (2000) Expression and assignment of the 1H, 15N, and 13C resonances of inhibitor-2, the inhibitor of protein phosphatase-1. J. Biomol. NMR 17, 359-360.
      • Watanabe, T., Huang, H.B., Horiuchi, A., Hsieh-Wilson, L., Allen, P.B., Shenolikar, S., Greengard, P. and Nairn, A.C. (2001) Protein phosphatase 1 regulation by inhibitors and targeting subunits. Proc. Natl. Acad. Sci. 98, 3080-3085.
      • Huang, H.B., Chen, Y.C., Horiuchi, A., Tsai, L.H., Liu, H.T., Chyan, C.L., Lin, F.M., Greengard, P., Nairn, A.C., Hsieh, M.J., Liu, C.K., Shiao, M.S., and Lin, T.H. (2001) Backbone 1H, 15N, and 13C resonance assignments of ARPP-19. J. Biomol. NMR 19, 383-384.
      • Chang, L.S., Chung, C., Huang, H.B., Lin, S.R. (2001) Purification and characterization of a chymotrypsin inhibitor from the venom of Ophiophagus hannah (king cobra). Biochem. Biophys. Res. Commun. 283, 862-867.
      • Chyan, C.L., Tang, T.C., Chen, Y.C., Liu, H.T., Lin, F.M., Liu, C.K., Hsieh, M.J., Shiao, M.S., Huang, H.B., and Lin, T.H*. (2001) Backbone 1H, 15N, and 13C resonance assignments of inhibitor-1—a protein inhibitor of protein phosphatase-1. J. Biomol. NMR 21, 287-288.
      • Gulledge, B., Aggen, J.B., Huang, H.-B., Nairn, A.C. and Chamberlin, R. (2002) The microcystins and nodularins: cyclic polypeptide inhibitors of PP1 and PP2A. Current Medicinal Chemistry 9, 1903-1915.
      • Hung, C.J., Huang, P.C., Lu, S.C., Li, Y.H., Huang, H.B., Lin, B.F., Chang, S.J., and Chou, H.F. (2002) Plasma homocysteine levels in Taiwanese vegetarians are higher than those of omnivores. J. Nutr. 132, 152-158.
      • Liu, H. T., Lin, T. H., Kuo, H. C., Chen, Y. C., Tsay, H. J., Jeng, H. H., Tsai, P. C., Shie, F. C., Chen, J. H., and Huang, H. B.* (2002) Identification of the alternative splice products encoded by the human protein phosphatase inhibitor-1 gene. Biochem. Biophys. Res. Commun. 291, 1293-1296.
      • Chang, L.S., Liou, J.C., Lin, S.R., and Huang, H.B. (2002) Purification and characterization of neurotoxin from the venom of Ophiophagus hannah (king cobra). Biochem. Biophys. Res. Commun. 294, 574-578.
      • Liu, W., Colby, D.A., Sheppeck, J.E., Huang, H.B., Nairn, A.C., and Chamberlin, A.R. (2003) The selective inhibition of phosphatase by natural toxin: the anhydride domain of tautomycin is not a primary factor in controlling PP1/PP2A Sselectivity. Bioorg. Med. Chem. Lett. 13, 1597-1600.
      • Colby, D.A., Liu, W., Sheppeck, J.E., Huang, H.B., Nairn, A.C., and Chamberlin, A.R. (2003) A new model of tautomycin-PP1 complex that is not analogous to the corresponding okadaic acid structure. Bioorg. Med. Chem. Lett. 13, 1601-1605.
      • Sung, Y.J., Cheng, C.I., Chen, C.S., Huang, H.B., Wu, P.C., Shiao, M.S., and Tsay, H.J. (2003) Distinct mechanisms account for b-amyloid toxicity in PC12 and Differentiated PC12 neuronal cells. J. Biomed. Sci. 10, 379-388.
      • Watanabe, T., da Cruz e Silva, E., Huang, H.B., Starkova, N., Kwon, Y.G., Horiuchi, A., Greengard, P., and Nairn, A.C. (2003) Preparation and characterization of recombinant protein phosphatase 1. Methods Enzymol. 366, 319-338.
      • Lin, T.H., Chen, Y.C., Chyan, C.L., Tsay, L.H., Tang, T.C., Jeng, H.H., Lin, F.M., and Huang, H.B.* (2003) Phosphorylation of glycogen synthase kinase of inhibitor-2 does not change its structure in free state. FEBS Lett. 554, 253-256.
      • Lin TH, Huang JW, Huang HB, Chen YC, Liu CY, Lo CJ, Tang TC. Chyan CL (2004) 1H, 15N, and 13C resonance assignments of complexed with the calmodulin-binding domain of protein phosphatase 2B. J. Biomol. NMR. 29, 531-532.
      • Lin, T.H., Huang, Y.C., Chin, M.L., Chen, Y.C., Jeng, H.H., Lin, F.M., Shiao, M.S., Horiuchi, A., Greengard, P., Nairn, A.C., and Huang, H.B.* (2004) Backbone 1H, 15N, and 13C resonance assignments of DARPP-32 (dopamine and cAMP-regulated phosphoprotein, Mr. 32,000)—a protein inhibitor of protein phosphatase-1 J. Biomol. NMR. 28, 413-414.
      • Lin TH, Huang HB, Wei HA, Shiao SH, Chen YC (2005) The effect of temperature and lipid on the conformational transition of gramicidin A in lipid vesicles. Biopolymers 78, 179-186.
      • Huang HB, ChiMC, Hsu WH, Liang WC, Lin LL (2005) Construction and one-step purification of Bacillus kaustophilus leucine aminopeptidase fused to the starch-binding domain of Bacillus sp. Strain TS-23 a-amylase. Biopro. Biosyst. Eng. 27, 389-398.
      • Chyan CL, Huang PC, Lin TH, Huang JW, Lin SS, Huang HB, Chen YC (2005) Purification, crystallization and preliminary crystallographic studies of a calmodulin-OLFp hybrid molecule. Acat. Cryst. F61, 785-787.
      • Lin TH, Tsai PC, Liu HT, Chen YC, Wang LS, Shie FK, Huang HB* (2005) Characterization of the protein phosphatase 1-binding motifs of inhibitor-2 and DARPP-32 by surface plasmon resonance. J. Biochem. 138, 697 – 700.
      • Chi MC, Huang HB, Liu JS, Wang WC, Liang WC, Lin LL (2006) Residues threonine 346 and leucine 352 are critical for the proper function of Bacillus kaustophilus leucine aminopeptidase. FEMS Microbiol. Lett. 260, 156-161.
      • Chen YM, Lee TH, Lee SJ, Huang HB, Huang R, Chou HN (2006) Comparison of protein phosphatase inhibition activies and mouse toxicities of microcystins. Toxicon 47, 742-746.
      • Chang LS, Lin SR, Huang HB (2006) Disulfide isomerization and thiol-disulfide exchange of long neurotoxins from the venom of Ophiophagus hannah. Arch. Biochem. Biophy. 454, 181-188.
      • Chen YR, Huang HB, Chyan CL, Shiao MS, Lin TH, Chen YC (2006) The effect of Ab conformation on the metal affinity and aggregation mechanism studies by circular dichroism spectroscopy. J. Biochem. 139, 733-740.
      • Chang LS, Chen KC, Lin SR, Huang HB (2006) Purification and characterization of Ophiophagus Hannah cytotoxin-like proteins. Toxicon 48, 429-436.
      • Liao MQ, Tzeng YI, Chang LY, Huang HB, Lin TH, Chyan CL, Chen YC (2007) The correlation between neurotoxicity, aggregative ability and secondary structure studies by sequence truncated Ab peptides. FEBS Let. 581, 1161-1165.
      • Huang HB*, Chen YC, Lee TT, Huang YC, Liu HT, Liu CK, Tsay HJ, Lin TH* (2007) Structural and biochemical characterization of inhibitor-1a. Proteins 68, 779-788.
      • Kao SC, Chen CY, Wang SL, Yang JJ, Hung WC, Chen YC, Lai NS, Liu HZ, Huang HL, Chen HC, Lin TH*, Huang HB* (2007) Identification of phostensin, a PP1 F-actin cytoskeleton targeting subunit. Biochem. Biophys. Res. Commum. 356, 594-598.
      • Chi MC, Liu JS, Wang WC, Lin LL*, Huang HB* (2007) Site-directed mutagenesis of the conserved Ala348 and Gly350 residues at the putative site of Bacillus kaustophilus leucine aminopeptidase. Biochimie (in press).
      • Chi MC, Lu RQ, Lin LL*, Huang HB* (2007) Characterization of Bacillus kaustophilus leucine aminopeptidase immobilized in Ca-alginate/k-carrageenan beads. Biochem. Eng. J. (in press).
      • Kao SC, Wang SL, Chen CY, Yen JY, Wang ZF, Huang HL, Li C, Chen HC, Liu SQ, Lai, NS*, Lin TH*, Huang HB* (2007) Phostensin caps to the pointed end of actin filaments and modulates actin dynamics (in preparation).

      Conference abstract

      • The Backbone Resonace Assignments of Inhibitor 1 - a Protein Inhibitor of Protein Phosphatase-1 Tzu-Chun Tang, Hsin-Tzu Liu, Hsien-Bin Huang, Yi-Chen Chen, Chia-Lin Chyan and Ta-Hsien Lin
      • The conformation Conversion of Gramicidin A from Double Helix to Helical Dimer in Phospholipids bilayer by Fluorescence Spectroscopy Spectroscopy Ta-Hsien Lin, Hsien-Bin Huang, H. -A. Wei, S. -H. Shiao, B.A. Wallace, Y.C. Chen
      • NMR Study of the Thr35-phosphorylated Inhibitor-1 Yi-Choang Huang, Tzu-Chen Tang, Yi-Chen Chen, Hsien-Bin Huang, Yu-Chie Chen and Ta-Hsien Lin
      • Unfolding Study of b-Amyloid Peptide by NMR Spectroscopy Ying-En Chen, Yi-Ru Chen, Chi-Jen Lo, Yi-Chen Chen, Chia-li Su, Hun-Gen Chang, Hsien-Bin Huang and Ta-Hsien Lin
      • Structural determination of the C-terminal domain of apolipoprotein E in lipid environment by NMR spectroscopy Chi-Jen Lo, Yi-Chen, Hui-Ling Wang, Han-Tsang Wu, Hung-Mei Chen, Hsien-Bin Huang and Ta-Hsien Lin
      • Inhibition of b-amyloid peptide aggregation by rational mutation Ying-En Chen, Chi-Jen Lo, Chih Ching Wang, Yi-Chen Chen, Chia-li Su, Hun-Gen Chang, Hsien-Bin Huang and Ta-Hsien Lin
      • Identification and Characterization of the Isoform of Human Inhibitor-1. P104 Liu HT, Tsai LH, Kuo HC, Chen JH, Huang HB
      • Biochemical Characterizaton of Human Inhibitor 1?. P103 Su LJ, Wang TF, Liu HT, Lin TH and Huang HB
      • Characterization of the interaction between protein phosphatase 1 and inhibitor-2 by structure-function analysis, peptide competition and plasmon resonance. Tsai PC, Jeng HH, Wang LH, Shie FK, Lin YH, Chen YC, Lin TH and Huang HB
      • Identification and characterization of phostensin, a novel protein phosphatase 1 F-actin cytoskeleton targeting subunit encoded by KIAA1949. P597 Kao SC, Chen CY, Wang SL, Hung WC and Huang HB
      ^ back

    • Research Funding

      96
      計畫名稱：生化與功能性分析Phostensin特性, 一個編碼在KIAA1949並把1-型蛋白質磷酸酯?標的到F-肌動蛋白之蛋白質
      計畫編號：96-2320-B-194-005-MY3 (1/3)
      計畫金額：1,770,000

      95
      計畫名稱：新型蛋白質1型磷酸水解?調控蛋白, H3P和PP1RL, 的生化與功能特性分析
      計畫編號：95-2320-B-194-005
      計畫金額： 1,020,000

      94
      計畫名稱：鑑別與功能特性分析新的蛋白質, H3P (心臟特有之1型蛋白質磷酸水解酵素結合蛋白)，一有潛力成為心肌損傷的鑑識標記蛋白
      計畫編號：94-2320-B-194-005-
      計畫金額：1,300,000

      93
      計畫名稱：1-型蛋白質磷酸水解脢與其抑制蛋白間之交互作用(3/3)
      計畫編號：93-2320-B-194-005
      計畫金額：1,697,400

      92 計畫名稱：1-型蛋白質磷酸水解脢與其抑制蛋白間之交互作用(2/3)
      計畫編號：92-2320-B-194-005
      計畫金額：1,642,800

      91 計畫名稱：1-型蛋白質磷酸水解脢與其抑制蛋白間之交互作用(1/3)
      計畫編號：91-2320-B-194-001
      計畫金額：1,858,800

      90
      計畫名稱： PP-1與其抑制蛋白間之分子結構和生化特性分析並純化腦神經細胞中新的PP-1結合蛋白(3/3)
      計畫編號：90-2320-B-194-001-
      計畫金額：1,157,200

      89
      計畫名稱：PP-1與其抑制蛋白間之分子結構和生化特性分析並純化腦神經細胞中新的PP-1結合蛋白(2/3)
      計畫編號：89-2320-B-194-004-
      計畫金額：1,158,400

      89
      計畫名稱：探討(A)1型－蛋白質磷酸水解抑制蛋白,DARPP-32和INHIBITOR(B)人類酯蛋白元E及B-
      計畫編號：89-2320-B-194-003-
      計畫金額：798,100
      89

      計畫名稱：PP-1與其抑制蛋白間之分子結構和生化特性分析並純化腦神經細胞中新的PP-1結合蛋白(1/3)
      計畫編號：89-2320-B-320-006-
      計畫金額：1,167,409

      88
      計畫名稱：腦部PROTEIN PHOSPHATASE-1結合蛋白之純化與特性分析並建立ATP-MG DEPENDENT PHOSPHATASE活性的調控機制
      計畫編號：88-2314-B-320-012-
      計畫金額：703,800

      87
      計畫名稱：PROTEIN PHOSPHATASE 1 與其抑制蛋白, DARPP-32 AND I-2, 間之交互作用與結構研究
      計畫編號：87-2732-B-320-001-
      計畫金額：604,200

      86
      計畫名稱：PROTEIN PHOSPHATASE 1 和 DARPP-32 間之交互作用與結構的研究
      計畫編號：86-2314-B-320-002-
      計畫金額：798,000

 

©2008 All Rights Reserved.  •  Designed by FP (Pan Cheng Tsung)