Associate Research Fellow/Tsai, Keng-Chang

蔡耿彰實驗室生活照Current position:Associate Research Fellow
Education:Ph.D., Institute of Life Science, National Tsing Hua University
Telephone:+886-2-2820-1999 ext. 6241(Office)、6251(Lab)
E-mail : tkc@nricm.edu.tw

Major Professional Experiences:
Adjunct Associate Professor, Ph.D. Program for Biotechnology in Medicine, Taipei Medical University (2016/05~now)
Assistant Research Fellow, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taiwan. (2013/07~2015/11)
Assistant Research Fellow, National Research Institute of Chinese Medicine, Taiwan. (2011/08~2013/07)
Postdoctoral Fellow, Genomics Research Center, Academia Sinica, Taiwan. (2005/10~2011/07)
Bio-Information Project Manager and Chinese-herb Database, Breadth Technology company (2004/02~2005/06)

Specialty:
 TCM Antibody Library, Phage Display Antibody/Peptide Library, Computer-aided Drug Design, Natural Product Database, Structural bio-informatics.

Research Description:
Our interest includes Four parts:
  1. To develop TCM antibody libraries for screening of targeted protein
  2. Finding receptor and ligand binding site with phage display peptide or antibody library platform to provide important 3D-QSAR and pharmacophore models which are employed to increase hits in screening active compounds/anti-compound antibodies.
  3. Affinity selection of Chinese herbal extracts and peptide phage library to obtain peptide sequence from which the most potential sequences are identified by experiment and computational molecular modeling and the target sequences are used to screen potential target protein for the disease diagnosis or analysis.3.
  4. Constructing a huge natural product database including Chinese Ancient Literatures, information of disease, protein targets, drug compounds, and natural-product compounds as well as pharmacophore models and docking strategy. 
Honor:  The 31th Symposium on Natural Products & Symposium on Pharmacy and Traditional Chinese Medicine (the first prize in TCM)
Chinese Publication:
  1. Chemical engineering and information, Vol.37, Application of Drug information in drug development.
  2. Wang-Chuan Chen*, Keng-Chang Tsai, Li-Wei Lin, Hui-Hsiung Lin, and  Chun-Chuan Shih.(2015) Investigation of Tyrosinase Inhibition by Chinese Herbal Medicine Small Molecules as Skin-whitening Ingredients, Taiwan Journal of Chinese Medicine. 13(1): 29-42.
  3. Li-Wei Lin, Yune-Fang Ueng, Keng-Chang Tsai, Hung-Ju Hsu, Chun-Chuan Shih, and Wang-Chuan Chen.* (2015) Investigation of Interaction between Shu-Gin-Hwai-Shen-tang and Anticoagulant Warfarin from the Perspective of Structural Biology, Taiwan Journal of Chinese Medicine. 13(1): 1-12.
    Published Papers:
Published Papers:
 NCBI PubMed :  Keng-Chang Tsai (Please click!!) 
 Google Scholar :  Keng-Chang Tsai (Please click!!)
  1. Tsai KC, Chang CD, Cheng MH, Lin TY, Lo YN, Yang TW, Chang FL, Chiang CW, Lee YC, Yen Yun. Chicken-Derived Humanized Antibody Targeting a Novel Epitope F2pep of Fibroblast Growth Factor Receptor 2: Potential Cancer Therapeutic Agent.(2019) ACS Omega 4 (1), 2387-2397
  2. Tsai KC, Hung PP, Cheng CF, Chen C, Tseng TS. Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches.(2019) RSC Advances 9 (16), 9308-9312
  3. Wang YH, Liou KT, Tsai KC, Liu HK, Yang LM, Chern CM, Shen YC. GSK-3 Inhibition through GLP-1R Allosteric Activation Mediates the Neurogenesis Promoting Effect of P7C3 after Cerebral Ischemic/Reperfusional Injury in Mice. Toxicol Appl Pharmacol. 2018 Oct 15;357:88-105. doi: 10.1016/j.taap.2018.08.023.
  4. Tsai KC, Chen-Wei Chiang CW, Lo YN, Chang FL, Lin TY, Chang CY, Chen WC, Lee YC. (2018) Generation and characterization of avian-derived anti-human CD19 single chain fragment antibodies. Anim Biotechnol. Anim Biotechnol. 2018 Sep 27:1-9. doi: 10.1080/10495398.2018.1486323.
  5. Kuo LY, Tseng PY, Lin YC, Liaw CC, Zhang LJ, Tsai KC, Lin ZH, Ho HO, Kuo YH. (2018) New Hirsutinolide-Type Sesquiterpenoids from Vernonia cinerea Inhibit Nitric Oxide Production in LPS-Stimulated RAW264.7 Cells. Planta Med. 2018 ;84(18):1348-1354. doi: 10.1055/a-0647-1901.
  6. Tseng TS, Tu IF, Chen HT, Lin LC, Tsai KC*, Wu SH, Chen C. (2018) Protein-DNA complex-guided discovery of the antibacterial lead E1 for restoring the susceptibility of Klebsiella Pneumoniae to polymyxin B by targeting the response regulator PmrA. Chem Commun (Camb). 2018 Jun 14;54(49):6372-6375. (共同通訊作者)
  7. Chang CY, Chang FL, Chiang CW, Lo YN, Lin TY, Chen WC, Tsai KC, Lee YC. (2018) Interaction of S17 Antibody with the Functional Binding Region of the Hepatitis B Virus Pre-S2 Epitope. Viral Immunol. 2018 May 30. doi: 10.1089/vim.2017.0200. 
  8. Hsu PH, Chiu DC, Wu KL, Lee PS, Jan JT, Cheng YE, Tsai KC, Cheng TJ, Fang JM. (2018) Acylguanidine derivatives of zanamivir and oseltamivir: Potential orally available prodrugs against influenza viruses. Eur J Med Chem. 2018 Jun 25;154:314-323.
  9. Wang PC, Chiu DC, Jan JT, Huang WI, Tseng YC, Li TT, Cheng TJ, Tsai KC, Fang JM. (2018) Peramivir conjugates as orally available agents against influenza H275Y mutant. Eur J Med Chem. 2018 Feb 10;145:224-234.
  10. Kuo TF, Chen TY, Jiang ST, Chen KW, Chiang YM, Hsu YJ, Liu YJ, Chen HM, Yokoyama KK, Tsai KC, Yeh HH, Chen YR, Yang MT, Yang CY, Yang WC. (2017) Protein disulfide isomerase a4 acts as a novel regulator of cancer growth through the procaspase pathway. Oncogene. 2017 Sep 28;36(39):5484-5496
  11. Tseng TS, Tsai KC, Chen C. (2017) Characterizing the structure-function relationship reveals the mode of action of a novel antimicrobial peptide, P1, from jumper ant Myrmecia pilosula. Mol Biosyst. 2017 Jun 1;13(6):1193-1201
  12. Chiu DC, Lin TC, Huang WI, Cheng TJ, Tsai KC, Fang JM. (2017, Nov). Peramivir analogues bearing hydrophilic side chains exhibit higher activities against H275Y mutant than wild-type influenza virus.. Org Biomol Chem, 15(46):9910-9922..
  13. Tseng T.S., Wang S.H., Chang T.W., Wei H.M., Wang Y.J., Tsai, K. C, Liao .Y.D, Chen C. (2016) Sarkosyl-Induced Helical Structure of an Antimicrobial Peptide GW-Q6 Plays an Essential Role in the Binding of Surface Receptor OprI in Pseudomonas aeruginosa. PLoS One.11:e0164597. 
  14. Wang, P. C., Fang, J. M., Tsai, K. C., Wang, S. Y., Huang, W. I., Tseng, Y. C., Cheng, Y. S., Cheng, T. J., and Wong, C. H. (2016) Peramivir Phosphonate Derivatives as Influenza Neuraminidase Inhibitors, Journal of medicinal chemistry 59, 5297-5310.
  15. Tseng, T. S., Lee, Y. C., Hsiao, N. W., Liu, Y. R., and Tsai, K. C.*(2016) Comparative study between 3D-QSAR and Docking-Based Pharmacophore models for potent Plasomodium falciparum dihydroorotate dehydrogenase inhibitors, Bioorganic & medicinal chemistry letters 26, 265-271.
  16. Tseng, T. S., Chuang, S. M., Hsiao, N. W., Chen, Y. W., Lee, Y. C., Lin, C. C., Huang, C., and Tsai, K. C.*(2016) Discovery of a potent cyclooxygenase-2 inhibitor, S4, through docking-based pharmacophore screening, in vivo and in vitro estimations, Molecular bioSystems 12, 2541-2551.
  17. Tsay, H. J., Huang, Y. C., Chen, Y. J., Lee, Y. H., Hsu, S. M., Tsai, K. C., Yang, C. N., Huang, F. L., Shie, F. S., Lee, L. C., and Shiao, Y. J. (2016) Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO, Journal of biomedical science 23, 27.
  18. Jian, J. W., Elumalai, P., Pitti, T., Wu, C. Y., Tsai, K. C., Chang, J. Y., Peng, H. P., and Yang, A. S. (2016) Predicting Ligand Binding Sites on Protein Surfaces by 3-Dimensional Probability Density Distributions of Interacting Atoms, PloS one 11, e0160315.
  19. Tseng, T. S., Tsai, K. C., Chen, W. C., Wang, Y. T., Lee, Y. C., Lu, C. K., Don, M. J., Chang, C. Y., Lee, C. H., Lin, H. H., Hsu, H. J., and Hsiao, N. W. (2015) Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 x 20 Dipeptides in Inhibiting Dopachrome Formation, Journal of agricultural and food chemistry 63, 6181-6188.
  20. Lo, S. N., Shen, C. C., Chang, C. Y., Tsai, K. C., Huang, C. C., Wu, T. S., and Ueng, Y. F. (2015) The Effect of Oxidation on Berberine-Mediated CYP1 Inhibition: Oxidation Behavior and Metabolite-Mediated Inhibition, Drug metabolism and disposition: the biological fate of chemicals 43, 1100-1107.
  21. Li, A., Yang, D., Zhu, M., Tsai, K. C., Xiao, K. H., Yu, X., Sun, J., and Du, L. (2015) Discovery of novel FFA4 (GPR120) receptor agonists with beta-arrestin2-biased characteristics, Future medicinal chemistry 7, 2429-2437.
  22. Lee, Y. C., Hsiao, N. W., Tseng, T. S., Chen, W. C., Lin, H. H., Leu, S. J., Yang, E. W., and Tsai, K. C.*(2015) Phage display-mediated discovery of novel tyrosinase-targeting tetrapeptide inhibitors reveals the significance of N-terminal preference of cysteine residues and their functional sulfur atom, Molecular pharmacology 87, 218-230.
  23. Lee, Y. C., Chen, W. C., Liang, M. H., Lee, C. H., Tsai, K. C., Chiang, J. R., Chiang, L. C., Chen, C. C., Chang, C. Y., Lee, C. H., Leu, S. J., and Yang, Y. Y. (2015) Single chain antibody fragment with serine protease inhibitory property capable of neutralizing toxicity of Trimeresurus mucrosquamatus venom, Biochemical and biophysical research communications 460, 170-176.
  24. Ho, C. W., Van Meervelt, V., Tsai, K. C., De Temmerman, P. J., Mast, J., and Maglia, G. (2015) Engineering a nanopore with co-chaperonin function, Science advances 1, e1500905.
  25. Chen, W. C., Tseng, T. S., Hsiao, N. W., Lin, Y. L., Wen, Z. H., Tsai, C. C., Lee, Y. C., Lin, H. H., and Tsai, K. C.*(2015) Discovery of highly potent tyrosinase inhibitor, T1, with significant anti-melanogenesis ability by zebrafish in vivo assay and computational molecular modeling, Scientific reports 5, 7995.
  26. Chang, Y. P., Huang, C. C., Shen, C. C., Tsai, K. C., and Ueng, Y. F. (2015) Differential inhibition of CYP1-catalyzed regioselective hydroxylation of estradiol by berberine and its oxidative metabolites, Drug metabolism and pharmacokinetics 30, 374-383.
  27. Hsiao, N. W., Tseng, T. S., Lee, Y. C., Chen, W. C., Lin, H. H., Chen, Y. R., Wang, Y. T., Hsu, H. J., and Tsai, K. C.*(2014) Serendipitous discovery of short peptides from natural products as tyrosinase inhibitors, Journal of chemical information and modeling 54, 3099-3111.
  28. Hong, B. T., Chen, C. L., Fang, J. M., Tsai, K. C., Wang, S. Y., Huang, W. I., Cheng, Y. S., and Wong, C. H. (2014) Oseltamivir hydroxamate and acyl sulfonamide derivatives as influenza neuraminidase inhibitors, Bioorganic & medicinal chemistry 22, 6647-6654.
  29. Chen, C. Y., Huang, C. C., Tsai, K. C., Huang, W. J., Huang, W. C., Hsu, Y. C., and Hsu, F. L. (2014) Evaluation of the Antihyperuricemic Activity of Phytochemicals from Davallia formosana by Enzyme Assay and Hyperuricemic Mice Model, Evidence-based complementary and alternative medicine : eCAM 2014, 873607.
  30. Chen, C. L., Lin, T. C., Wang, S. Y., Shie, J. J., Tsai, K. C., Cheng, Y. S., Jan, J. T., Lin, C. J., Fang, J. M., and Wong, C. H. (2014) Tamiphosphor monoesters as effective anti-influenza agents, European journal of medicinal chemistry 81, 106-118.
  31. Lo, S. N., Chang, Y. P., Tsai, K. C., Chang, C. Y., Wu, T. S., and Ueng, Y. F. (2013) Inhibition of CYP1 by berberine, palmatine, and jatrorrhizine: selectivity, kinetic characterization, and molecular modeling, Toxicology and applied pharmacology 272, 671-680.
  32. Lee, Y. C., Tsai, K. C., Leu, S. J., Wang, T. J., Liu, C. Y., and Yang, Y. Y. (2013) Isolation, characterization, and molecular modeling of a rheumatoid factor from a Hepatitis C virus infected patient with Sjogren's syndrome, TheScientificWorldJournal 2013, 516516.
  33. Yu, C. M., Peng, H. P., Chen, I. C., Lee, Y. C., Chen, J. B., Tsai, K. C., Chen, C. T., Chang, J. Y., Yang, E. W., Hsu, P. C., Jian, J. W., Hsu, H. J., Chang, H. J., Hsu, W. L., Huang, K. F., Ma, A. C., and Yang, A. S. (2012) Rationalization and design of the complementarity determining region sequences in an antibody-antigen recognition interface, PloS one 7, e33340.
  34. Tsai, K. C., Jian, J. W., Yang, E. W., Hsu, P. C., Peng, H. P., Chen, C. T., Chen, J. B., Chang, J. Y., Hsu, W. L., and Yang, A. S. (2012) Prediction of carbohydrate binding sites on protein surfaces with 3-dimensional probability density distributions of interacting atoms, PloS one 7, e40846.
  35. Chen, H. J., Shen, Y. C., Lin, C. Y., Tsai, K. C., Lu, C. K., Shen, C. C., and Lin, Y. L. (2012) Metabolomics Study of Buyang Huanwu Tang Decoction in Ischemic Stroke Mice by 1H NMR, Metabolomics 8, 974-984.
  36. Chen, C. T., Peng, H. P., Jian, J. W., Tsai, K. C., Chang, J. Y., Yang, E. W., Chen, J. B., Ho, S. Y., Hsu, W. L., and Yang, A. S. (2012) Protein-protein interaction site predictions with three-dimensional probability distributions of interacting atoms on protein surfaces, PloS one 7, e37706.
  37. Zhang, L., Tsai, K. C., Du, L., Fang, H., Li, M., and Xu, W. (2011) How to generate reliable and predictive CoMFA models, Current medicinal chemistry 18, 923-930.
  38. Yang, F. L., Yang, Y. L., Liao, P. C., Chou, J. C., Tsai, K. C., Yang, A. S., Sheu, F., Lin, T. L., Hsieh, P. F., Wang, J. T., Hua, K. F., and Wu, S. H. (2011) Structure and immunological characterization of the capsular polysaccharide of a pyrogenic liver abscess caused by Klebsiella pneumoniae: activation of macrophages through Toll-like receptor 4, The Journal of biological chemistry 286, 21041-21051.
  39. Shie, J. J., Fang, J. M., Lai, P. T., Wen, W. H., Wang, S. Y., Cheng, Y. S., Tsai, K. C., Yang, A. S., and Wong, C. H. (2011) A practical synthesis of zanamivir phosphonate congeners with potent anti-influenza activity, Journal of the American Chemical Society 133, 17959-17965.
  40. Wen, W. H., Wang, S. Y., Tsai, K. C., Cheng, Y. S., Yang, A. S., Fang, J. M., and Wong, C. H. (2010) Analogs of zanamivir with modified C4-substituents as the inhibitors against the group-1 neuraminidases of influenza viruses, Bioorganic & medicinal chemistry 18, 4074-4084.
  41. Tsai, K. C., Chen, Y. C., Hsiao, N. W., Wang, C. L., Lin, C. L., Lee, Y. C., Li, M., and Wang, B. (2010) A comparison of different electrostatic potentials on prediction accuracy in CoMFA and CoMSIA studies, European journal of medicinal chemistry 45, 1544-1551.
  42. Ho, C. W., Popat, S. D., Liu, T. W., Tsai, K. C., Ho, M. J., Chen, W. H., Yang, A. S., and Lin, C. H. (2010) Development of GlcNAc-inspired iminocyclitiols as potent and selective N-acetyl-beta-hexosaminidase inhibitors, ACS chemical biology 5, 489-497.
  43. Yang, Q., Du, L. P., Tsai, K. C., Wang, X. J., Li, M. Y., and You, Q. D. (2009) Pharmacophore Mapping for Kv1.5 Potassium Channel Blockers, QSAR Comb. Sci. 28, 59-71.
  44. Wang, S. Y., Tseng, C. P., Tsai, K. C., Lin, C. F., Wen, C. Y., Tsay, H. S., Sakamoto, N., Tseng, C. H., and Cheng, J. C. (2009) Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq, Biochemical and biophysical research communications 385, 230-235.
  45. Tsai, K. C., Teng, L. W., Shao, Y. M., Chen, Y. C., Lee, Y. C., Li, M., and Hsiao, N. W. (2009) The first pharmacophore model for potent NF-kappaB inhibitors, Bioorganic & medicinal chemistry letters 19, 5665-5669.
  46. Tsai, K. C., Wang, S. H., Hsiao, N. W., Li, M., and Wang, B. (2008) The effect of different electrostatic potentials on docking accuracy: a case study using DOCK5.4, Bioorganic & medicinal chemistry letters 18, 3509-3512.
  47. Shao, Y. M., Yang, W. B., Kuo, T. H., Tsai, K. C., Lin, C. H., Yang, A. S., Liang, P. H., and Wong, C. H. (2008) Design, synthesis, and evaluation of trifluoromethyl ketones as inhibitors of SARS-CoV 3CL protease, Bioorganic & medicinal chemistry 16, 4652-4660.
  48. Lu, I. L., Tsai, K. C., Chiang, Y. K., Jiaang, W. T., Wu, S. H., Mahindroo, N., Chien, C. H., Lee, S. J., Chen, X., Chao, Y. S., and Wu, S. Y. (2008) A three-dimensional pharmacophore model for dipeptidyl peptidase IV inhibitors, European journal of medicinal chemistry 43, 1603-1611.
  49. Hsu, H. J., Tsai, K. C., Sun, Y. K., Chang, H. J., Huang, Y. J., Yu, H. M., Lin, C. H., Mao, S. S., and Yang, A. S. (2008) Factor Xa active site substrate specificity with substrate phage display and computational molecular modeling, The Journal of biological chemistry 283, 12343-12353.
  50. Shie, J. J., Fang, J. M., Wang, S. Y., Tsai, K. C., Cheng, Y. S., Yang, A. S., Hsiao, S. C., Su, C. Y., and Wong, C. H. (2007) Synthesis of tamiflu and its phosphonate congeners possessing potent anti-influenza activity, Journal of the American Chemical Society 129, 11892-11893.
  51. Shao, Y. M., Yang, W. B., Peng, H. P., Hsu, M. F., Tsai, K. C., Kuo, T. H., Wang, A. H., Liang, P. H., Lin, C. H., Yang, A. S., and Wong, C. H. (2007) Structure-based design and synthesis of highly potent SARS-CoV 3CL protease inhibitors, Chembiochem : a European journal of chemical biology 8, 1654-1657.
  52. Tsai, K. C., Chen, S. Y., Liang, P. H., Lu, I. L., Mahindroo, N., Hsieh, H. P., Chao, Y. S., Liu, L., Liu, D., Lien, W., Lin, T. H., and Wu, S. Y. (2006) Discovery of a novel family of SARS-CoV protease inhibitors by virtual screening and 3D-QSAR studies, Journal of medicinal chemistry 49, 3485-3495.
  53. Lu, I. L., Mahindroo, N., Liang, P. H., Peng, Y. H., Kuo, C. J., Tsai, K. C., Hsieh, H. P., Chao, Y. S., and Wu, S. Y. (2006) Structure-based drug design and structural biology study of novel nonpeptide inhibitors of severe acute respiratory syndrome coronavirus main protease, Journal of medicinal chemistry 49, 5154-5161.
  54. Lin, T. H., Chiu, S. H., and Tsai, K. C. (2006) Supervised feature ranking using a genetic algorithm optimized artificial neural network, Journal of chemical information and modeling 46, 1604-1614.
  55. Zheng, Z. L., Zuo, Z. Y., Liu, Z. G., Tsai, K. C., Liu, A. F., and Zou, G. L. (2005) Construction of a 3D model of nattokinase, a novel fibrinolytic enzyme from Bacillus natto. A novel nucleophilic catalytic mechanism for nattokinase, Journal of molecular graphics & modelling 23, 373-380.
  56. Wei, H. Y., Tsai, K. C., and Lin, T. H. (2005) Modeling ligand-receptor interaction for some MHC class II HLA-DR4 peptide mimetic inhibitors using several molecular docking and 3D QSAR techniques, Journal of chemical information and modeling 45, 1343-1351.
  57. Li, M. Y., Tsai, K. C., and Xia, L. (2005) Pharmacophore identification of alpha(1A)-adrenoceptor antagonists, Bioorganic & medicinal chemistry letters 15, 657-664.
  58. Du, L. P., Li, M. Y., Tsai, K. C., You, Q. D., and Xia, L. (2005) Characterization of binding site of closed-state KCNQ1 potassium channel by homology modeling, molecular docking, and pharmacophore identification, Biochemical and biophysical research communications 332, 677-687.
  59. Tsai, K. C., and Lin, T. H. (2004) A ligand-based molecular modeling study on some matrix metalloproteinase-1 inhibitors using several 3D QSAR techniques, Journal of chemical information and computer sciences 44, 1857-1871.
  60. Liu, H. C., Lyu, P. C., Leong, M. K., Tsai, K. C., and Hsiue, G. H. (2004) 3D-QSAR studies on PU3 analogues by comparative molecular field analysis, Bioorganic & medicinal chemistry letters 14, 731-734.
  61. Lin, T. H., Li, H. T., and Tsai, K. C. (2004) Implementing the Fisher's discriminant ratio in a k-means clustering algorithm for feature selection and data set trimming, Journal of chemical information and computer sciences 44, 76-87.
  62. Du, L. P., Tsai, K. C., Li, M. Y., You, Q. D., and Xia, L. (2004) The pharmacophore hypotheses of I(Kr) potassium channel blockers: novel class III antiarrhythmic agents, Bioorganic & medicinal chemistry letters 14, 4771-4777.
  63. Lin, T. H., Tsai, K. C., and Lo, T. C. (2003) Homology modeling of the central catalytic domain of insertion sequence ISLC3 isolated from Lactobacillus casei ATCC 393, Protein engineering 16, 819-829.