徐祖安

TA Hsu 2徐祖安  研究員
生技與藥物研究所
Email: tsuanhsu@nhri.edu.tw

 

CURRENT APPOINTMENTS

  • Investigator, Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes
  • Professor, Department of Biological Science and Technology, National Chiao-Tung University

EDUCATION

  • Ph.D.1996, Chemical Engineering, The Johns Hopkins University, Baltimore, MD, USA.
  • B.S. 1989, Chemical Engineering, National Taiwan University, Taipei, Taiwan.

PROFESSIONAL EXPERIENCES

  • 06/2013 – 08/2015: Director General, Administration Department of NHRI.
  • 10/1998 – 04/2008: Assistant Investigator, Associate Investigator, and Investigator.
    Institute of Biotechnology and Pharmaceutical Research, NHRI
  • 04/1997 – 10/1998: Senior Research Chemical Engineer
    Vaccine Pharmaceutical Research, Merck & Co., West Point, Pennsylvania, USA.
  • 02/1996- 03/1997: Post-doctoral Fellow Protein Development,
    Human Genome Sciences, Inc., Rockville, Maryland, USA.
  • 06/1992 – 12/1993: Visiting Researcher
    School of Medicine,The Johns Hopkins University
  • 07/1989 – 05/1991: Instructor Army, Taiwan.

RESEARCH INTERESTS

  • Anti-cancer and antiviral drug discovery & development
  • Protein Engineering/Cell Culture Engineering

RESEARCH ACTIVITIES & ACCOMPLISHMENTS

Dr. Hsu has authored or co-authored more than 100 original research articles, several invited review articles and book chapters. He is an inventor for 8 US patents. Over the past 20 years, he has participated in projects involving novel gene discovery (at Human Genome Sciences), pediatric vaccine development (at Merck), and drug discovery at NHRI for SARS coronavirus (SARS-CoV), enterovirus 71 (EV71), hepetitic C virus (HCV), influenza virus, diabetes. Recently, he becomes interested in developing novel drugs for cancers with human kinases as the molecular targets.
Core capability: Protein Engineering, Cancer Biology, Drug Repositioning.

HONORS

  1. Wu, Da-Yo Memorial Award (吳大猷先生紀念獎), National Science Council, Taiwan, 2006.
  2. Ten Outstanding Young Persons of the Republic of China (ROC), 2006.
  3. Ten Rising Stars in Taiwan, 2007.
  4. 2007 NHRI Young Scientist Award.
  5. The National Innovation Award (國家新創獎) , 2013.

SELECTED PUBLICATIONS

Please refer to National Health Research Institutes Institutional Repository

http://ir.nhri.edu.tw/handle/3990099045/17?locale=en-US

  1. Bispecific Antibody Conjugated MnMEIO for HER2/neu- and EGFR-Expressing Tumor Imaging. Accepted for publication.
  2. Wu JS, Lin SY, Liao FY, Hsiao WC, Lee LC, Peng YH, Hsieh CL, Wu MH, Song JS, Yueh A et al: Identification of Substituted Naphthotriazolediones as Novel Tryptophan 2,3-Dioxygenase (TDO) Inhibitors through Structure-Based Virtual Screening. J Med Chem 2015, 58(19):7807-7819.
  3. Hsu KC, Sung TY, Lin CT, Chiu YY, Hsu JT, Hung HC, Sun CM, Barve I, Chen WL, Huang WC et al: Anchor-based classification and type-C inhibitors for tyrosine kinases. Scientific reports 2015, 5:10938.
  4. Lin WH, Yeh TK, Jiaang WT, Yen KJ, Chen CH, Huang CT, Yen SC, Hsieh SY, Chou LH, Chen CP et al: Evaluation of the Antitumor Effects of BPR1J-340, a Potent and Selective FLT3 Inhibitor, Alone or in Combination with an HDAC Inhibitor, Vorinostat, in AML Cancer. PloS one 2014, 9(1):e83160.
  5. Hung HC, Shih SR, Chang TY, Fang MY, Hsu JT: The combination effects of licl and the active leflunomide metabolite, A771726, on viral-induced interleukin 6 production and EV-A71 replication. PloS one 2014, 9(11):e111331.
  6. Wu J-M, Chen C-T, Coumar MS, Lin W-H, Chen Z-J, Hsu JT-A, Peng Y-H, Shiao H-Y, Lin W-H, Chu C-Y et al: Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules. Proc Natl Acad Sci U S A 2013, 110(19):E1779-1787.
  7. Lin HM, Wang JC, Hu HS, Wu PS, Wang WH, Wu SY, Yang CC, Yeh TK, Hsu TA, Jiaang WT et al: Resistance Studies of a Dithiazol Analogue, DBPR110, as a Potential Hepatitis C Virus NS5A Inhibitor in Replicon Systems. Antimicrobial Agents and Chemotherapy 2013, 57(2):723-733.
  8. Lin CH, Chang TC, Das A, Fang MY, Hung HC, Hsu KC, Yang JM, von Itzstein M, Mong KKT, Hsu TA et al: Synthesis of acylguanidine zanamivir derivatives as neuraminidase inhibitors and the evaluation of their bio-activities. Organic & Biomolecular Chemistry 2013, 11(24):3943-3948.
  9. Lin WH, Jiaang WT, Chen CW, Yen KJ, Hsieh SY, Yen SC, Chen CP, Chang KY, Chang CY, Chang TY et al: BPR1J-097, a novel FLT3 kinase inhibitor, exerts potent inhibitory activity against AML. British Journal of Cancer 2012, 106(3):475-481.
  10. Lin HM, Wang JC, Hu HS, Wu PS, Yang CC, Wu CP, Pu SY, Hsu TA, Jiaang WT, Chao YS et al: Resistance Analysis and Characterization of a Thiazole Analogue, BP008, as a Potent Hepatitis C Virus NS5A Inhibitor. Antimicrobial Agents and Chemotherapy 2012, 56(1):44-53.
  11. Lai Y-K, Hsu JT-A, Chu C-C, Chang T-Y, Pan K-L, Lin C-C: Enhanced recombinant protein production and differential expression of molecular chaperones in sf-caspase-1-repressed stable cells after baculovirus infection. BMC Biotechnol 2012, 12:83.
  12. Hsu JTA, Yeh TK, Yen SC, Chen CT, Hsieh SY, Hsu T, Lu CT, Chen CH, Chou LH, Chiu CH et al: 3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3). Bioorganic & Medicinal Chemistry Letters 2012, 22(14):4654-4659.
  13. Hsu JTA, Yeh JY, Lin TJ, Li ML, Wu MS, Hsieh CF, Chou YC, Tang WF, Lau KS, Hung HC et al: Identification of BPR3P0128 as an Inhibitor of Cap-Snatching Activities of Influenza Virus. Antimicrobial Agents and Chemotherapy 2012, 56(2):647-657.
  14. Chiu HC, Chang TY, Huang CT, Chao YS, Hsu JTA: EGFR and myosin II inhibitors cooperate to suppress EGFR-T790M-mutant NSCLC cells. Molecular Oncology 2012, 6(3):299-310.
  15. Wang YJ, Pan KL, Hsieh TC, Chang TY, Lin WH, Hsu JTA: Diosgenin, a Plant-Derived Sapogenin, Exhibits Antiviral Activity in Vitro against Hepatitis C Virus. Journal of Natural Products 2011, 74(4):580-584.
  16. Lin WH, Hsieh SY, Yen SC, Chen CT, Yeh TK, Hsu T, Lu CT, Chen CP, Chen CW, Chou LH et al: Discovery and evaluation of 3-phenyl-1H-5-pyrazolylamine-based derivatives as potent, selective and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3). Bioorganic & Medicinal Chemistry 2011, 19(14):4173-4182.
  17. Hung HC, Wang HC, Shih SR, Teng IF, Tseng CP, Hsu JTA: Synergistic Inhibition of Enterovirus 71 Replication by Interferon and Rupintrivir. Journal of Infectious Diseases 2011, 203(12):1784-1790.
  18. Hsu J, Chiu H, Chou D, Huang C, Lin W, Lien T, Yen K: Suppression of Stat3 Activity Sensitizes Gefitinib-resistant Non Small Cell Lung Cancer Cells. European Journal of Cancer 2011, 47:S104-S104.
  19. Chu CC, Pan KL, Yao HT, Hsu JTA: Development of a Whole-Cell Screening System for Evaluation of the Human CYP1A2-Mediated Metabolism. Biotechnology and Bioengineering 2011, 108(12):2932-2940.
  20. Chiu HC, Chou DL, Huang CT, Lin WH, Lien TW, Yen KJ, Hsu JTA: Suppression of Stat3 activity sensitizes gefitinib-resistant non small cell lung cancer cells. Biochemical Pharmacology 2011, 81(11):1263-1270.
  21. Cheung CHA, Lin WH, Hsu JTA, Hour TC, Yeh TK, Ko SK, Lien TW, Coumar MS, Liu JF, Lai WY et al: BPR1K653, a Novel Aurora Kinase Inhibitor, Exhibits Potent Anti-Proliferative Activity in MDR1 (P-gp170)-Mediated Multidrug-Resistant Cancer Cells. PloS one 2011, 6(8).
  22. Wu CH, Coumar MS, Chu CY, Lin WH, Chen YR, Chen CT, Shiao HY, Rafi S, Wang SY, Hsu H et al: Design and Synthesis of Tetrahydropyridothieno 2,3-d pyrimidine Scaffold Based Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors: The Role of Side Chain Chirality and Michael Acceptor Group for Maximal Potency. Journal of Medicinal Chemistry 2010, 53(20):7316-7326.
  23. Shih SR, Horng JT, Poon LLM, Chen TC, Yeh JY, Hsieh HP, Tseng SN, Chiang C, Li WL, Chao YS et al: BPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses. Journal of Antimicrobial Chemotherapy 2010, 65(1):63-71.
  24. Hung HC, Chen TC, Fang MY, Yen KJ, Shih SR, Hsu JTA, Tseng CP: Inhibition of enterovirus 71 replication and the viral 3D polymerase by aurintricarboxylic acid. Journal of Antimicrobial Chemotherapy 2010, 65(4):676-683.
  25. Coumar MS, Chu CY, Lin CW, Shiao HY, Ho YL, Reddy R, Lin WH, Chen CH, Peng YH, Leou JS et al: Fast-Forwarding Hit to Lead: Aurora and Epidermal Growth Factor Receptor Kinase Inhibitor Lead Identification. Journal of Medicinal Chemistry 2010, 53(13):4980-4988.
  26. Pan KL, Lee JC, Sung HW, Chang TY, Hsu JTA: Development of NS3/4A Protease-Based Reporter Assay Suitable for Efficiently Assessing Hepatitis C Virus Infection. Antimicrobial Agents and Chemotherapy 2009, 53(11):4825-4834.
  27. Lin CH, Peng YH, Coumar MS, Chittimalla SK, Liao CC, Lyn PC, Huang CC, Lien TW, Lin WH, Hsu JTA et al: Design and Structural Analysis of Novel Pharmacophores for Potent and Selective Peroxisome Proliferator-activated Receptor gamma Agonists. Journal of Medicinal Chemistry 2009, 52(8):2618-2622.
  28. Kang IJ, Wang LW, Lee CC, Lee YC, Chao YS, Hsu TA, Chern JH: Design, synthesis, and anti-HCV activity of thiourea compounds. Bioorganic & Medicinal Chemistry Letters 2009, 19(7):1950-1955.
  29. Hung HC, Tseng CP, Yang JM, Ju YW, Tseng SN, Chen YF, Chao YS, Hsieh HP, Shih SR, Hsu JTA: Aurintricarboxylic acid inhibits influenza virus neuraminidase. Antiviral research 2009, 81(2):123-131.
  30. Hsieh HP, Coumarrs MS, Chu CY, Ho YL, Tsai MT, Lin WH, Chen CH, Song JS, Hsu JTA, Chao YS: Fast-forwarding kinase drug discovery: aurora and EGFR kinase inhibitor lead development. Ejc Supplements 2009, 7(2):96-96.
  31. Hsieh HP, Coumar MS, Lin CW, Reddy GR, Tsai MT, Lin WH, Hsu TA, Wu SY: Discovery and development of novel furano-pyrimidine analogs as Aurora kinase inhibitors. Abstracts of Papers of the American Chemical Society 2009, 237.
  32. Coumar MS, Leou JS, Shukla P, Wu JS, Dixit AK, Lin WH, Chang CY, Lien TW, Tan UK, Chen CH et al: Structure-Based Drug Design of Novel Aurora Kinase A Inhibitors: Structural Basis for Potency and Specificity. Journal of Medicinal Chemistry 2009, 52(4):1050-1062.
  33. Chen TC, Chang HY, Lin PF, Chern JH, Hsu JTA, Chang CY, Shih SR: Novel Antiviral Agent DTriP-22 Targets RNA-Dependent RNA Polymerase of Enterovirus 71. Antimicrobial Agents and Chemotherapy 2009, 53(7):2740-2747.
  34. Su CT, Hsu JTA, Hsieh HP, Lin PH, Chen TC, Kao CL, Lee CN, Chang SY: Anti-HSV activity of digitoxin and its possible mechanisms. Antiviral research 2008, 79(1):62-70.
  35. Lin WH, Song JS, Chang TY, Chang CY, Fu YN, Yeh CL, Wu SH, Huang YW, Fang MY, Lien TW et al: A cell-based high-throughput screen for epidermal growth factor receptor pathway inhibitors. Analytical Biochemistry 2008, 377(1):89-94.
  36. Lee JC, Shih SR, Chang TY, Tseng HY, Shih YF, Yen KJ, Chen WC, Shie JJ, Fang JM, Liang PH et al: A mammalian cell-based reverse two-hybrid system for functional analysis of 3C viral protease of human enterovirus 71. Analytical Biochemistry 2008, 375(1):115-123.
  37. Hwang DR, Chang CW, Lien TW, Chen WC, Tan UK, Hsu JTA, Hsieh HP: Synthesis and anti-viral activity of a series of sesquiterpene lactones and analogues in the subgenomic HCV replicon system. Bioorganic & Medicinal Chemistry 2006, 14(1):83-91.
  38. Hsu JTA, Wang HC, Chen GW, Shih SR: Antiviral drug discovery targeting to viral proteases. Current Pharmaceutical Design 2006, 12(11):1301-1314.
  39. Leu GZ, Lin TY, Hsu JTA: Anti-HCV activities of selective polyunsaturated fatty acids (vol 318, pg 275, 2004). Biochemical and Biophysical Research Communications 2005, 329(4):1360-1360.
  40. Hsieh HP, Wu YS, Lu PH, Chen CM, Chao YC, Jan JT, Huei-Ru L, Ma SH, Chao YS, Hsu TA: Promazine analogues as potential anti SARS-CoV drugs. Abstracts of Papers of the American Chemical Society 2005, 229:U168-U168.
  41. Hsieh HP, Mahindroo N, Wang CC, Huang CF, Lien TW, Tsai CH, Peng YH, Lee LH, Prakash E, Chen WC et al: Design and structure-activity relationships of novel indole-based PPAR agonists as antidiabetic agents. Abstracts of Papers of the American Chemical Society 2005, 229:U141-U141.
  42. Hsieh HP, Mahindroo N, Coumar MS, Wang CC, Huang CF, Lien TW, Tsai CH, Lin YT, Lee LH, Prakash E et al: Design, synthesis and sar of indole-based PPAR agonists. Abstracts of Papers of the American Chemical Society 2005, 229:U141-U141.
  43. Chen CN, Lin CPC, Huang KK, Chen WC, Hsieh HP, Liang PH, Hsu JTA: Inhibition of SARS-CoV 3C-like protease activity by theaflavin-3,3 ‘- digallate (TF3). Evidence-Based Complementary and Alternative Medicine 2005, 2(2):209-215.
  44. Wu CJ, Jan JT, Chen CM, Hsieh HP, Hwang DR, Liu HW, Liu CY, Huang HW, Chen SC, Hong CF et al: Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide. Antimicrobial Agents and Chemotherapy 2004, 48(7):2693-2696.
  45. Leu GZ, Lin TY, Hsu JTA: Anti-HCV activities of selective polyunsaturated fatty acids. Biochemical and Biophysical Research Communications 2004, 318(1):275-280.
  46. Lee JC, Chang CF, Chi YH, Hwang DR, Hsu JTA: A reporter-based assay for identifying hepatitis C virus inhibitors based on subgenornic replicon cells. Journal of Virological Methods 2004, 116(1):27-33.
  47. Kuo CJ, Chi YH, Hsu JTA, Liang PH: Characterization of SARS main protease and inhibitor assay using a fluorogenic substrate. Biochemical and Biophysical Research Communications 2004, 318(4):862-867.
  48. Kuo CJ, Chi YH, Hsu JTA, Liang PH: Characterization of SARS main protease and inhibitor assay using a fluorogenic substrate (vol 318, pg 862, 2004). Biochemical and Biophysical Research Communications 2004, 320(2):623-623.
  49. Hwang DR, Tsai YC, Lee JC, Huang KK, Lin RK, Ho CH, Chiou JM, Lin YT, Hsu JTA, Yeh CT: Inhibition of hepatitis C virus replication by arsenic trioxide. Antimicrobial Agents and Chemotherapy 2004, 48(8):2876-2882.
  50. Hsu JTA, Kuo CJ, Hsieh HP, Wang YC, Huang KK, Lin CPC, Huang PF, Chen X, Liang PH: Evaluation of metal-conjugated compounds as inhibitors of 3CL protease of SARS-CoV. Febs Letters 2004, 574(1-3):116-120.
  51. Chern JH, Shia KS, Hsu TA, Tai CL, Lee CC, Lee YC, Chang CS, Tseng SN, Shih SR: Design, synthesis, and struc-ture-activity relationships of pyrazolo 3,4-d pyrimidinies: a novel class of potent enterovirus inhibitors. Bioorganic & Medicinal Chemistry Letters 2004, 14(10):2519-2525.
  52. Betenbaugh MJ, Tomiya N, Narang S, Hsu JTA, Lee YC: Biosynthesis of human-type N-glycans in heterollogous systems. Current Opinion in Structural Biology 2004, 14(5):601-606.
  53. Wu JM, Lin JC, Chieng LL, Lee CK, Hsu TA: Combined use of GAP and AOX1 promoter to enhance the expression of human granulocyte-macrophage colony-stimulating factor in Pichia pastoris. Enzyme and Microbial Technology 2003, 33(4):453-459.
  54. Lee JC, Shih YF, Hsu SP, Chang TY, Chen LH, Hsu JTA: Development of a cell-based assay for monitoring specific hepatitis C virus NS3/4A protease activity in mammalian cells. Analytical Biochemistry 2003, 316(2):162-170.
  55. Hu YC, Hsu JTA, Huang JH, Ho MS, Ho YC: Formation of enterovirus-like particle aggregates by recombinant baculoviruses co-expressing P1 and 3CD in insect cells. Biotechnology Letters 2003, 25(12):919-925.
  56. Burke CJ, Hsu TA, Volkin DB: Formulation, stability, and delivery of live attenuated vaccines for human use. Critical Reviews in Therapeutic Drug Carrier Systems 1999, 16(1):1-83.
  57. Wang CY, Ni J, Jiang H, Hsu TA, Dugich-Djordjevic M, Feng L, Zhang M, Mei L, Gentz R, Lu B: Cloning and characterization of glial cell line-derived neurotrophic factor receptor-B: A novel receptor for members of glial cell line-derived neurotrophic factor family of neurotrophic factors. Neuroscience 1998, 83(1):7-14.
  58. Hsu TA, Takahashi N, Tsukamoto Y, Kato K, Shimada I, Masuda K, Whiteley EM, Fan JQ, Lee YC, Betenbaugh MJ: Differential N-glycan patterns of secreted and intracellular IgG produced in Trichoplusia ni cells. Journal of Biological Chemistry 1997, 272(14):9062-9070.
  59. Hsu TA, Betenbaugh MJ: Coexpression of molecular chaperone BiP improves immunoglobulin solubility and IgG secretion from Trichoplusia ni insect cells. Biotechnology Progress 1997, 13(1):96-104.
  60. Hsu TA, Watson S, Eiden JJ, Betenbaugh MJ: Rescue of immunoglobulins from insolubility is facilitated by PDI in the baculovirus expression system. Protein Expression and Purification 1996, 7(3):281-288.
  61. Betenbaugh MJ, Ailor E, Whiteley E, Hinderliter P, Hsu TA: Chaperone and foldase coexpression in the baculovirus-insect cell expression system. Cytotechnology 1996, 20(1-3):149-159.
  62. Hsu TA, Eiden JJ, Bourgarel P, Meo T, Betenbaugh MJ: EFFECTS OF CO-EXPRESSING CHAPERONE BIP ON FUNCTIONAL ANTIBODY-PRODUCTION IN THE BACULOVIRUS SYSTEM. Protein Expression and Purification 1994, 5(6):595-603.
  63. Hsu TA, Eiden JJ, Betenbaugh MJ: ENGINEERING THE ASSEMBLY PATHWAY OF THE BACULOVIRUS-INSECT CELL EXPRESSION SYSTEM. In: Recombinant DNA Technology Ii. Edited by Bajpai RK, Prokop A, vol. 721; 1994: 208-217.

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