國立中興大學基因體暨生物資訊學研究所

　　

　　 　　

　　　　　　　

　　　　　　　

　　　　　　　

基因體暨生物資訊學研究所

Graduate Institute of Genomics and Bioinformatics

Chinese
English

興大首頁

National Chung Hsing University

醫科博班

Doctoral Program in Medical Biotechnology

生命科學院

College of Life Sciences

Hou, Ming-Hon

Lab: Drug Design and Chemical Biology Core Lab

Experience

Title Department Period
Professor NCHU, Institute of Genomics and Bioinformatics 2013.08–Now
Associate Professor NCHU, Institute of Genomics and Bioinformatics 2010.02– 2013.07
Adjunct Assistant Professor NCHU, Graduate Institute of Biotechnology 2008.8-2010.01
Joint Assistant Professor NCHU, Department of Life Sciences 2008.8-2010.01
Joint Assistant Professor NCHU, Biotechnology Center 2008.8-2010.01
Assistant Professor NCHU Institute of Genomics and Bioinformatics 2008.08 – 2010.01
Assistant Professor NCHU, Biotechnology Center 2007.02-2008.07
Assistant Professor Shih Chien University, Department of Food Science, Nutrition, and Nutraceutical Biotechnology 2004.8-2007.1
Postdoctoral Fellow Institute of Biological Chemistry, Academia Sinica 2003.8-2004.7
Ph.D. NTU, Institute of Biochemical Sciences 1999.09-2003.07
M.S. NCHU, Graduate Institute Of Biochemistry 1997.09-1999.07

Research

Research Interests
  1. Protein Engineering
  2. Structural Biology
  3. Drug Design
  4. Biophysics

Lectures:

Course

Genetics, Bioinformatics: Lecture and Experiment, Protein Engineering, Structural Bioinformatics, Special Topics in Biotechnology, Applied Genomics and Bioinformatics: Lecture and Experiment, Special Topics in Biotechnology

Research

Lab Research
Our major research projects include:

  • Development of antiviral drugs targeting the nucleoside protein against emerging viruses.
  • Development of anticancer drugs targeting DNA or RNA.
  • Development of diagnostic tools for genetic diseases associated with unusual DNA structures.

 

In order to solve the health problems that human beings are facing today, our lab focuses on the development of novel drugs against several important infectious diseases, genetic diseases, and cancers. Our specialty research field can be divided into two parts: (1) Developing nucleic acid-binding drugs for cancer therapy and investigating the mechanisms of these anti-cancer drugs and (2) Investigating the function and structure of nucleoside proteins from viruses, such as coronavirus and influenza virus, and developing new anti-viral drugs. These two aspects of our research focus on developing essential therapy drugs for important diseases that affect all humankind.

Our group showed that the binding of Chromomycin A3 to the repetitive DNA duplex can induce the conformational changes in the DNA structure in presence of the metal ions. This study is a useful contribution towards the use of the metalloantibiotic not only for the therapeutic but also for the diagnostic purposes in neurological diseases (Angew Chem Int Ed Engl in 2017). On the other hand, we solve the crystal structure of the CCG triplet repeats sequence with i-motif structure related to neurological disease. Our observation of this i-motif structure provides a molecular-level pathological consequence of DNA expansion (Angew Chem Int Ed Engl in 2014). Furthermore, we discovered that the drug actinomycin D can also bind to repetitive DNA sequences to induce the sharp bends in the DNA with flipping out of the bases. This study was a very useful contribution from our group against the drug development for the neurological diseases due to DNA repeat expansions (NAR in 2013).

In addition, we are also interested in developing the novel antiviral agents against the various respiratory viruses including coronavirus and influenza virus. We have studied the coronaviruses 229E and OC43 as experimental models, specifically focusing on nucleocapsid protein. In these analyses, we have examined its biochemistry, biophysics, immunology, and its potential as a target for antiviral drugs. In our recent findings of the N protein of coronavirus, we propose guidelines for developing new N protein-based antiviral agents that target CoVs (Journal of medicinal chemistry, 2014). Influenza spreads very rapidly and has a high mortality rate. Tamiflu (oseltamivir), which is a neuraminidase inhibitor, is used to treat patients. However, several H1N1 influenza strains are known to be resistant to Tamiflu because of the H274Y mutation in neuraminidase. In order to find out the new drugs acting on the nucleoprotein of the influenza virus, we develop a fluorescence-based assay to monitor nucleoprotein binding to a potential inhibitor. This assay can also be useful in screening the new drugs against the other viral proteins also such as HBV or HIV (Analytical Chemistry in 2012).

Publications

Journal(*Corresponding author)
    1. Roshan Satange, Chien-Ying Chuang, Stephen Neidle and Ming-Hon Hou*. (2019) Polymorphic G:G mismatches act as hotspots for inducing right-handed Z DNA by DNA intercalation. Nucleic Acids Research, 47(16):8899–8912.
    2. Chen YW; Satange R; Wu PC; Jhan CR; Chang CK; Chung KR; Waring MJ; Lin SW; Hsieh LC; Hou MH*.(2018) CoII(Chromomycin)2 complex induces a conformational change of CCG repeats from i-Motif to base-extruded DNA duplex. International Journal of Molecular Sciences
    3. Wu PC, Tzeng SL, Chang CK, Kao YF, Waring MJ, Hou MH*. (2018) Cooperative recognition of T:T mismatch by echinomycin causes structural distortions in DNA duplex Nucleic Acids Research
    4. Satange R; Chang CK; Hou, MH*. (2018) A survey of recent unusual high-resolution DNA structures provoked by mismatches, repeats and ligand binding. Nucleic acids research
    5. Liu CH, Chen YT, Hou MH, Hu NJ, Chen CS, Shaw JF. (2018) Crystallographic analysis of the Staphylococcus epidermidis lipase involved in esterification in aqueous solution. Acta Crystallographica Section F-Structural Biology Communications
    6. Huang TY; Chang CK; Kao YF; Chin CH; Ni CW; Hsu HY; Hu NJ; Hsieh LC; Chou SH; Lee IR; Hou MH*. (2017) Parity-dependent hairpin configurations of repetitive DNA sequence promote slippage associated with DNA expansion. Proceedings of the National Academy of Sciences of the United States of America
    7. Tseng WH; Chang CK; Wu PC; Hu NJ; Lee GH; Tzeng CC; Neidle S; Hou MH*. (2017) Induced-fit recognition of CCG trinucleotide repeats by a nickel chromomycin complex results in large-scale DNA deformation. Angewandte Chemie-International Edition
    8. Lin YH; Chuang SM; Wu PC; Chen CL; Jeyachandran S; Lo SC; Huang HS; Hou MH*. (2016) Selective recognition and stabilization of new ligands targeting the potassium form of the human telomeric G-quadruplex DNA. Scientific Reports
    9. Liu CL; Hung HC; Lo SC; Chiang CH; Chen IJ; Hsu JT; Hou MH*. (2016) Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development. Scientific Reports
    10. Hou MH; Chuang CY; Ko TP; Hu NJ; Chou CC; Shih YP; Ho CL; Wang AH. (2016) Crystal structure of vespid phospholipase A(1) reveals insights into the mechanism for cause of membrane dysfunction. Insect Biochemistry And Molecular Biology
    11. Chang CK; Jeyachandran S; Hu NJ; Liu CL; Lin SY; Wang YS; Chang YM; Hou MH*. (2016) Structure-based virtual screening and experimental validation of the discovery of inhibitors targeted towards the human coronavirus nucleocapsid protein. Molecular Biosystems
    12. Wang YS; Chang CK; Hou MH*. (2015) Crystallographic analysis of the N-terminal domain of Middle East respiratory syndrome coronavirus nucleocapsid protein. Acta Crystallographica Section F-Structural Biology Communications
    13. Lin, S.Y., Liu, C.L., Chang, Y.M., Zhao, J., Perlman, S. and Hou,M.H.(2014) Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target. Journal of medicinal chemistry, 57, 2247-2257.
    14. Chang, C.K., Hou, M.H., Chang, C.F., Hsiao, C.D. and Hou,M.H.(2014) The SARS coronavirus nucleocapsid protein–forms and functions. Antiviral research, 103, 39-50.
    15. Chen, I.J., Yuann, J.M., Chang, Y.M., Lin, S.Y., Zhao, J., Perlman, S., Shen, Y.Y., Huang, T.H. and Hou,M.H.(2013) Crystal structure-based exploration of the important role of Arg106 in the RNA-binding domain of human coronavirus OC43 nucleocapsid protein. Biochimica et biophysica acta, 1834, 1054-1062.
    16. Lo, Y.S., Tseng, W.H., Chuang, C.Y. and Hou,M.H.(2013). The structural basis of actinomycin D-binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats. Nucleic Acids Res 41, 4284-94.
    17. Chen, Y.W. and Hou,M.H.(2013) The binding of the Co(II) complex of dimeric chromomycin A3 to GC sites with flanking G:G mismatches. Journal of inorganic biochemistry, 121, 28-36.
    18. Lo, Y.S., Lin, S.Y., Wang, S.M., Wang, C.T., Chiu, Y.L., Huang, T.H. and Hou,M.H.(2013). Oligomerization of the carboxyl terminal domain of the human coronavirus 229E nucleocapsid protein. FEBS Lett 587, 120-7.
    19. Liang, F.Y., Lin, L.C., Ying, T.H., Yao, C.W., Tang, T.K., Chen, Y.W. and Hou,M.H.(2013). Immunoreactivity characterisation of the three structural regions of the human coronavirus OC43 nucleocapsid protein by Western blot: implications for the diagnosis of coronavirus infection. J Virol Methods 187, 413-20.
    20. Kuo, S.M., Kao, H.W., Hou,M.H., Wang, C.H., Lin, S.H. and Su, H.L. (2013). Evolution of infectious bronchitis virus in Taiwan: positively selected sites in the nucleocapsid protein and their effects on RNA-binding activity. Vet Microbiol 162, 408-18.
    21. Hsu, C.W., Kuo, C.F., Chuang, S.M. and Hou,M.H.(2013). Elucidation of the DNA-interacting properties and anticancer activity of a Ni(II)-coordinated mithramycin dimer complex. Biometals 26, 1-12.
    22. Chen, Y.W. and Hou,M.H.(2013). The binding of the Co(II) complex of dimeric chromomycin A3 to GC sites with flanking G:G mismatches. J Inorg Biochem 121, 28-36.
    23. Yuann, J.M., Tseng, W.H., Lin, H.Y. and Hou,M.H.(2012). The effects of loop size on Sac7d-hairpin DNA interactions. Biochim Biophys Acta 1824, 1009-15.
    24. Wu, M.R.,Hou,M.H., Lin, Y.L. and Kuo, C.F. (2012). 2,4,5-TMBA, a natural inhibitor of cyclooxygenase-2, suppresses adipogenesis and promotes lipolysis in 3T3-L1 adipocytes. J Agric Food Chem 60, 7262-9.
    25. Wang, S.Y. et al. (2012). Spermine attenuates the action of the DNA intercalator, actinomycin D, on DNA binding and the inhibition of transcription and DNA replication. PLoS One 7, e47101.
    26. Hung, H.C. et al. (2012). Development of an anti-influenza drug screening assay targeting nucleoproteins with tryptophan fluorescence quenching. Anal Chem 84, 6391-9.
    27. Hsu, C.W., Chuang, S.M., Wu, W.L. and Hou,M.H. (2012). The crucial role of divalent metal ions in the DNA-acting efficacy and inhibition of the transcription of dimeric chromomycin A3. PLoS One 7, e43792.
    28. Chang, Y.M., Chen, C.K. and Hou,M.H.(2012). Conformational Changes in DNA upon Ligand Binding Monitored by Circular Dichroism. Int J Mol (SCI) 13, 3394-413.
  • Chang, Y.M., Chen, C.K., Chang, Y.C., Jeng, W.Y.,Hou,M.H. and Wang, A.H. (2012). Functional studies of ssDNA binding ability of MarR family protein TcaR from Staphylococcus epidermidis. PLoS One 7, e45665.
  • Kuo, S.M., Wang, C.H.,Hou,M.H., Huang, Y.P., Kao, H.W. and Su, H.L. (2010). Evolution of infectious bronchitis virus in Taiwan: characterisation of RNA recombination in the nucleocapsid gene. Vet Microbiol 144, 293-302.
  • Chen, I.J., Chou, C.C., Liu, C.L., Lee, C.C., Kan, L.S. and Hou,M.H.(2010). Crystallization and preliminary X-ray diffraction analysis of the N-terminal domain of human coronavirus OC43 nucleocapsid protein. Acta Crystallogr Sect F Struct Biol Cryst Commun 66, 815-8.
  • Lu, W.J., Wang, H.M., Yuann, J.M., Huang, C.Y. andHou, M.H.(2009). The impact of spermine competition on the efficacy of DNA-binding Fe(II), Co(II), and Cu(II) complexes of dimeric chromomycin A(3). J Inorg Biochem 103, 1626-33.>
  • Huang, C.Y., Hsu, Y.L., Chiang, W.L. and Hou, M.H.(2009). Elucidation of the stability and functional regions of the human coronavirus OC43 nucleocapsid protein. Protein (SCI) 18, 2209-18.
  • Hou, M.H., Lu, W.J., Lin, H.Y. and Yuann J.M. (2008) Studies of sequence-specific DNA binding, DNA cleavage, and topoisomerase I Inhibition by the dimeric chromomycin A3 complexed with Fe(II). Biochemistry., 47, 5493-5502.
  • Tang, T.K., Wu, P.J., Chen, S.T., Hou, M.H., Hong, M.H., Pan, F.M., Yu, H.M., Chen, J.H., Yao, C.W. and Wang, A.H.-J. (2005) Biochemical and immunological studies of nucleocapsid proteins of severe acute respiratory and 229E human coronaviruses.. Proteomics 5,925-37.
  • Hou, M.H. and Wang A.H.-J. (2005) Mithramycin forms a stable dimeric complex by chelating with Fe(II): DNA-interacting characteristics, cellular permeation and cytotoxicity. Nucleic Acids Res. 33,1352-61
  • Hou, M.H., Robinson H., Gao Y.G. and Wang A.H.-J. (2004) Crystal structure of the Mg2+-(chromomycin A3)2-d(TTGGCCAA)2 complex reveals GGCC binding specificity of the drug dimer chelated by metal ion. Nucleic Acids Res, 32, 2214-2222. (Featured on Cover)
  • Hou, M.H., Robinson H., Gao Y.G. and Wang A.H.-J. (2002). Crystal structure of actinomycin D bound to the CTG triplet repeat sequences linked to neurological diseases. Nucleic Acids Res., 30, 4910-4917. (Featured on Cover)
  • Hou, M.H., Lin, S.B., Yuann J.M., Lin W.C., Wang A.H.-J. and Kan L.S. (2001) Effects of polyamines on the thermal stability and formation kinetics of DNA duplexes with abnormal structure. Nucleic Acids Res., 29, 5121-5128.

 

Conference (*Invited speaker)
      1. Ming-Hon Hou (2019, Feb) Structure-based virtual screening and experimental validation of novel human coronavirus nucleocapsid protein anti-viral inhibitors. In: Structure Assisted Development of Novel Therapeutics 2019; 2019 Feb 12-16. Faridabad, India (Speech, Feb 15 , VI).
      2. Roshan Satange and Ming-Hon Hou*(2019, Feb) Structural heterogeneity in DNA duplex with symmetric G:G mismatches upon CoII(Chromomycin A3)2 and Actinomycin D binding.In: Structure Assisted Development of Novel Therapeutics 2019; 2019 Feb 12-16. Faridabad, India. (Poster)
      3. Roshan Satange and Ming-Hon Hou*(2018, May) Synergistic intercalation of echinomycin and actinomycin D to DNA duplex with T:T mismatch causes single strand deformation. pp.104(Poster). In: The 23rd Biophysics Conference; 2018 May 23-25; Taichung, Taiwan
      4. Yun-Jean Lin and Ming-Hon Hou*(2018, May) Structural study of the specific interactions between echinomycin and methylated DNA containing the CCG motif .pp.103(Poster). In: The 23rd Biophysics Conference; 2018 May 23-25; Taichung, Taiwan
      5. Hsiang-Ti Huang and Ming-Hon Hou*(2018, May) Structural basis for the binding of Echinomycin to DNA duplex containing I:C mismatch. pp.91(Poster). In: The 23rd Biophysics Conference; 2018 May 23-25; Taichung, Taiwan
      6. Pei-Ching Wu, Shu-Ling Tzeng, Chung-ke Chang, Ya-Fen Kao, Michael J. Waring and Ming-Hon Hou* (2018, May) Cooperative recognition of T:T mismatch by echinomycin causes structural distortions in DNA duplex. pp.106(Poster). In: The 23rd Biophysics Conference; 2018 May 23-25; Taichung, Taiwan
      7. Ching-Ming Chien, Jia-Ning Hsu and Ming-Hon Hou* (2018, May) Homology Modeling and Crystallization of N-terminal domain of Porcine Epidemic Diarrhea Virus Nucleocapsid Protein. pp.90(Poster). In: The 23rd Biophysics Conference; 2018 May 23-25; Taichung,Taiwan
      8. Jing-Yi Zeng, Tzu-Jung Huang and Ming-Hon Hou* (2018, May) The terminal base pairs determine the conformation of DNA duplex with G:T mismatch. pp.117(Poster). In: The 23rd Biophysics Conference; 2018 May 23-25; Taichung, Taiwan
      9. Ming-Hon Hou (2018, May) Binding of small molecules to trinucleotide DNA repeats associated with fragile X syndrome. pp.34(Oral). In: The 23rd Biophysics Conference; 2018 May 23-25; Taichung, Taiwan
      10. Hou, MH; Hsu, CN (Dec, 2017) Structural basis for identification of the interface of the N-terminal domain of CoV N protein dimer as a target for drug development. pp. 196 (Abstract POS501). In: the 31st Annual Symposium ofThe Protein Society, 2017 July 24–27, Montreal, Canada.
      11. Lin, S.Y., Liu, C.L., Chang, Y.M., and Hou, M.H.*(2012, Dec). Probing the N-terminal domain of coronavirus nucleocapsid protein as a potent target for antiviral drug development.. 2012 Taiwan Society for Biochemistry and Molecular Biology.
      12. Lin, Y.H., Chen, C.L., Huang, H.S., and Hou, M.H.* (2012, Dec). The study of anthrax[1, 2-d] imidazole-6,11-dione derivatives bound to the potassium form of human telomere G-quadruplex.. 2012 Taiwan Society for Biochemistry and Molecular Biology.
      13. Chen, Y.W., andHou, M.H.* (2012, Dec). The binding of the Co(II) complex of dimeric chromomycin A3 to GC sites with flanking G:G mismatches.. 2012 Taiwan Society for Biochemistry and Molecular Biology.
      14. Tseng, W. H., Yuann, J. M., Lin, H. Y., and Hou, M.H.*(2012). The effects of loop size on Sac7d-hairpin DNA interactions.. 17th Joint International Conference of Biophysics and Annual Conference of the Biophsical Society of ROC.
      15. Hou, M.H.*., Liu, C.L., Chen, I.J. and Chou, C.C. (2011). Identification of the N-terminal domain of human coronaviral nucleocapsid protein as a potential antiviral target. The 36th FEBS congress.
      16. Hsu, CW., Chuang, S.M. and Hou, M.H.* (2011). Comparison of DNA-binding properties and ant proliferative effects for chromomycin A3 dimer chelated with various divalent metal ions. 22nd FAOBMB conference.
      17. Liu, C.L., Chen, I.J. and Hou, M.H.*(2011). Identification of the N-terminal domain of human coronaviral nucleocapsid protein as a potential antiviral target . 22nd FAOBMB conference.
      18. Chen, Y.W. and Hou, M.H.*(2010). Probing the interaction of the residue Y148 in influenza A virus nucleoprotein involved in RNA-binding. The Taiwan society for biochemistry and molecular biology.
      19. Hou, M.H.* Lu,W.J., Wang, H.M., Yuann, J.M., and Huang, C.Y. (2010). The impact of spermine competition on the efficacy of DNA-binding Fe(II), Co(II), and Cu(II) complexes of dimeric chromomycin A(3). 4th Asian Bioinorganic Chemistry Conference.
      20. Hou, M.H.*, Lu,W.J., Huang, C.Y., Fan, R.J., and Yuann, J.M. (2010). Effects of polyamines on the DNA-reactive properties of dimeric mithramycin complexed with cobalt(II): implications for anticancer therapy . 24th International Conference on Organometallic Chemistry.
      21. Lo, Y.S., Chiu, Y.L. and Hou, M.H.*(2010). The crucial role of C-terminal tail of human coronavirus 229E nucleocapsid protein in oligomerization. The Taiwan society for biochemistry and molecular biology.
      22. Chiang, C.H., Wu, F.C. and Hou, M.H.*(2009). Probing the crucial residues of influenza virus (H1N1) nucleocapsid for RNA-bunding. 14th Joint International Conference of Biophysics and Annual Conference of the Biophsical Society of ROC.
      23. Chiu, Y.L, Lo, Y.S. and Hou, M.H.*(2009). Characterization of the C-terminal domain of human coronavirus 229E nucleocapsid protein in RNA-binding and oligomerization. 14th Joint International Conference of Biophysics and Annual Conference of the Biophisical Society of ROC.
      24. Hou, M.H.* Chiang, C. H., Wu, F. C. and Lo, Y. S. (2009). Probing the crucial residues of influenza virus (H1N1) nucleoprotein for RNA-binding. VIII European Symposium of The Protein Society.