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侯明宏

侯明宏 [教授兼所長]

E-MAIL:
mhho@dragon.nchu.edu.tw
研究室:
藥物設計及化學生物核心實驗室
研究方向:
  • 藥物設計
  • 生物物理
  • 蛋白質工程
實驗室位置:
動植物防檢疫大樓7樓712室
實驗室電話:
(04)22840338 分機 7121
辦公室位置:
動植物防檢疫大樓7樓701室
辦公室電話:
(04)22840338 分機 7011
傳真:
(04)22859329

簡要經歷

職稱 服務單位 起訖年月
教授 中興大學 基因體暨生物資訊學研究所 2013.08–迄今
副教授 中興大學 基因體暨生物資訊學研究所 2010.02– 2013.07
兼任助理教授 中興大學 生物科技研究所 2008.8-2010.01
合聘助理教授 中興大學 生命科學系 2008.8-2010.01
合聘助理教授 中興大學 生物科技發展中心 2008.8-2010.01
助理教授 中興大學 基因體暨生物資訊所 2008.08 – 2010.01
助理教授 中興大學生物科技發展中心 2007.02-2008.07
助理教授 實踐大學食品營養與保健生技學系 2004.8-2007.1
博士後研究員 中央研究院生物化學所 2003.8-2004.7
博士 國立台灣大學生化科學所 1999.09-2003.07
碩士 國立中興大學生物化學所 1997.09-1999.07

榮譽:

名稱
  1. 中興大學優秀青年教師獎(2010和 2012年)
  2. 中興大學研究績優獎 (2013年)
  3. 資深優良教師 (2014年)
  4. 特聘教授(2015年)
  5. 傑出人才發展基金會第三屆年輕學者創新獎(2015年)
  6. 104年度「傑出化學家青年獎」(2015年)
  7. 第11屆永信李天德青年醫藥科技獎(2015年)

教學與研究

研究方向
  1. 蛋白質工程
  2. 結構生物
  3. 藥物設計
  4. 生物物理

教授課程:

課程名稱

遺傳學(生科系)、生物資訊學暨實習(生科系)、蛋白質工程學(基資所)、結構生物資訊學(基資所)、生物技術特論(生技博)、應用基因體學及生物資訊學暨實習(基資所)、生物化學特論(生技博)

研究主題

實驗室研究方向

核酸結合抗癌藥物機制之探討

冠狀病毒之核殼蛋白功能和結構探討

抗病毒藥物開發

 

本實驗室之研究領域主要分為兩個部份:(1) 感冒病毒(HCoV-229E、HCoV-OC43與H1N1)之核殼蛋白與核酸結合功能和結構探討;(2)抗癌藥物之研發與抗癌機制之探討,分述如下:

 

1. 感冒病毒之核殼蛋白與核酸結合功能和結構探討:

 

冠狀病毒之核殼蛋白與核酸結合功能和結構之探討

自從2002年冬到2003年春,SARS冠狀病毒肆虐全球,並造成嚴重急性呼吸道症候群(Severe Acute Respiratory Syndrome,SARS),此時全世界再次興起冠狀病毒的研究風潮。依照血清學分析,人類冠狀病毒229E及OC43分屬於冠狀病毒之第一群組和第二群組,此二種病毒主要會引起人類急性上呼吸道感染,為一般人類普通感冒之主要致病原。人類冠狀病毒229E及OC43之核殼蛋白(nucleocapsid protein)為病毒主要結構蛋白之一,為一個高電荷、高親水性的鹼性蛋白質。此種蛋白的主要功能是與病毒RNA結合,並形成螺旋狀的核殼結構(nucleocapsid structure),進一步組成核醣核殼蛋白複合體(ribonucleoprotein,RNP)而形成病毒的核心,使病毒RNA在恆定的構形下進行複製與轉錄。截至目前為止,還沒有任何文獻是針對人類冠狀病毒229E和OC43核殼蛋白之生物化學及生物物理的特性來進行研究。經過序列比對後發現,冠狀病毒之核殼蛋白雖具有些許保留端,但彼此間的相似性卻不高,因此推測冠狀病毒核殼蛋白之生物化學及生物物理的特性也會有所不同。本實驗室主要是針對人類冠狀病毒229E和OC43核殼蛋白之生物化學、生物物理及免疫學的特性進行一些重要的研究,計劃的結果也將會對於藥物、疫苗及診斷方法的開發有相當大的幫助。

 

A型流感病毒H1N1核殼蛋白之穩定性及其核酸結合功能與結構之探討

流感病毒在分類學上屬於正黏液病毒科(Orthomyxoviridae),分為A、B、C三型。其中人類常見的A型流感病毒有西班牙流感(H1N1)、亞洲流感(H2N2)與香港流感(H3N2),本實驗室以A型流感病毒H1N1作為研究的病毒株,來了解其核殼蛋白之特性。H1N1核殼蛋白(nucleoprotein)分子量為56kDa,會結合到病毒的genome RNA,從ribonucleoprotein(RNP)複合物起約間隔20個nucleotides。流感病毒之核殼蛋白主要的功能是包裹病毒的核酸,並且在病毒的增生的過程中扮演調節的角色,其中包括複製(replication)、轉錄(transcription)、包裝(packaging)與病毒的成熟(maturation)。此外,核殼蛋白也會與感染細胞的蛋白產生交互作用,包括actin、nuclear import components、export apparatus與nuclear RNA helicase。本實驗室主要針對H1N1核殼蛋白進行生物化學與生物物理方面之相關研究,以解開其結構與功能的奧秘。

2. 核酸結合之抗癌藥物研發與抗癌機制探討:

本研究題目主要是以抗癌藥與目標物的結合機制及其在癌症疾病的治療作一系列的探討。抗生素Mithramycin 和Chromomycin A3 是一種鍵結於DNA的aureolic 類抗癌藥物。 其活性主要來自於干擾DNA的複製及轉錄作用,並運用於臨床的癌症治療上。此類藥物藉由單一的二價金屬離子鍵結於富含G/C的DNA雙螺旋序列組成的次溝(minor groove)上,而明顯使次溝變得比先前寬闊。在之前的研究證實,當沒有DNA的情況下,二價金屬離子可以形成金屬離子aureolic 類藥物聚合體。現今有許多的抗癌藥物會利用金屬離子所結合行成的複合物而導致癌細胞的死亡,可以增加其應用在人類惡性腫瘤治療的潛力。因此本計劃我們將研究aureolic類抗癌藥物與其他不同金屬離子構成複合物的能力(結合力和相對配位),並且評估此類聚合物的生化功能、抑制topoisomerase I及細胞毒性。

著作

期刊論文(*Corresponding author)
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.>
  21. 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.
  22. 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.
  23. 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.
  24. 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
  25. 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)
  26. 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)
  27. 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.

研討會論文 (*Invited speaker)
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Hou, M.H. and Huang, C.Y. (2008). Functional domains identification of human coronavirus 229E nucleocapsid protein. The 22nd Symposium of The Protein Society.
  16. Liang, F.Y., Lin, T.J., Hsu, Y.L., Ying, T.H. and Hou, M.H. (2008). Prokaryotic expression and antigenicity analysis of human coronavirus OC43 nucleocapsid protein. 23th Joint Annual Conference of Biomedical Sciences, Taipei, Taiwan.
  17. Hou, M.H. and Huang, C.Y. (2007). The Studies of Biochemcal Properties and Stability of Recombinant Human Coronavirus OC43 Nucleocapsid Protein.. The 21st Symposium of The Protein Society.
  18. Hou, M.H., Hsu, Y.L., Huang, C.Y. and Chiang, W.L. (2007). Characterization of human coronavirus OC43 nucleocapsid protein. Experimental Biology Annual Meeting 2007.
  19. Hou, M.H., Lin, H.Y., Lu, W.J., Kan, L.S., and Wang, A.H.-J. DNA-binding characterization of the dimeric chromomycin A3 complex chelated with Fe(II) ion : sequence preference, DNA cleavage and topoisomerase I inhibition. 21th Joint Annual Conference of Biomedical Sciences, Taipei, Taiwan. (Abstract)
  20. Hou, M.H., Hsu, Y.L., Tang, T.K., Yao, C.W., and Wang, A.H.-J. Biochemical and stability studies of recombinant human coronavirus OC43 nucleocapsid protein. 21th Joint Annual Conference of Biomedical Sciences, Taipei, Taiwan. (Abstract)
  21. Hou, M.H., Robinson H., Gao Y.G. and Wang A.H.-J. The interference mechanism of actinomycin D bound to CTG triplet repeat associated with myotonic dystrophy. 13th Symposium on Recent Advances in Cellular and Molecular Biology (Abstract)
  22. Hou, M.H., Robinson H., Gao Y.G. and Wang A.H.-J. Crystal structure of actinomycin D bound to the CTG triplet repeat sequences linked to neurological diseases. The 8th Symposium on Recent Advances in Biophysics (Abstract)
  23. Hou, M.H., Robinson H., Gao Y.G. and Wang A.H.-J. Crystal structure of the Mg2+-(chromomycin A3)2-d(TTGGCCAA)2 complex reveals GGCC binding specificity of the drug dimer chelated by metal ion. 4th East Asian Biophysics Symposium (Abstract)
  24. Hou, M.H., Kan L.S. and Lin S.B. Stability of DNA duplex re-visit: The effect of polyamine. The 4th Symposium on Recent Advances in Biophysics (Abstract)
  25. Hou, M.H., Kan L.S. and Lin S.B. The kinetic study of the effect of polyamine on the formation of A-T base pair-rich DNA duplexes by surface plasmon resonance. The 5th Symposium on Recent Advances in Biophysics (Abstract)
  26. Hou,M.H., Hsu, Y.L., Huang, C.Y. and Chiang, W.L. Characterization of human coronavirus OC43 nucleocapsid protein. Experimental Biology Annual Meeting 2007 ( Abstract)
  27. Hou,M.H. and Huang, C.Y., The Studies of Biochemcal Properties and Stability of Recombinant Human Coronavirus OC43 Nucleocapsid Protein. The 21st Symposium of The Protein Society 2007 (Abstract)
  28. Hou,M.H. and Huang, C.Y., Functional domains identification of human coronavirus 229E nucleocapsid protein. The 22nd Symposium of The Protein Society 2008 (Abstract)