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胡文熙

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胡文熙, Ph.D.

教授

Ph D, University of Minnesota . U.S.A

 

 

 

 

 

 

 

 

 

 

 

 

 

Experience
Chairman, Institute of Biotechnoloqy in Medicine/Facutly of Biotechnology and Laboratory Science in Medcine, National Yang- Ming University
Research Scientist, Walter Reed Army Medical Center . Washington, DC

Research Interests
There are two research subjects in my laboratory.

1. Regulation of mycoplasmal IS1550 transposase production
We have previously isolated and identified a transposable element IS1550 from Mycoplasma fermentans. This element encodes two open reading frames (ORFs), ORF1 and ORF2. Firstly, we proved IS1550 is transposable in Escherichia coli. Second, two proteins 16-kDa and 50-kDa were expressed in E. coli T7 expression system. The 16-kDa protein was determined to be encoded by ORF1, whereas, the 50-kDa protein was determined to be encoded by forming the fusion of ORF1 and ORF2 through an efficient –1 translational frameshift mechanism. Site-directed mutagenesis and dural-reporter gene system have been applied to determine a shifty site, AAAAAAA, and a stimulatory sequence, IIR to result in –1 frameshifting in IS1550. Third, we examined the effect of 16-kDa protein on the –1 frameshifting efficiency. The results showed that the 16-kDa protein could bind to the frameshift signal DNA region and resulted in a truncated mRNA. This protein could repress the –1 frameshift product both in vivo and in vitro. Thus, we propose that 16-kDa protein could repress on the –1 frameshift product by blocking the RNA polymerase proceeding and resulted in the decreasing of the putative transposase (50-kDa) production. This novel finding provides us for further study of regulation of transposase production.
2. The mechanism of antibiotic resistance in bacteria
The key factor to solve antibiotic resistance in bacteria is to understand resistant mechanism. We studied resistance to ceftriaxone in Salmonella enterica serovar Typhimurium, particulary in permeability and efflux pump. We were able to screen the mutants decreased resistance to ceftriaxone in an insertion mutant library constructed by transposon mutagenesis of S. enterica serovar Typhimurium. Mutant 7F2 has a transposon inserted in the regulator gene baeR of BaeSR two-component system. And showed a more –than-fourfold reduction in resistance to ceftriaxone. Complementation analysis suggested that one or both the outer membrane proteins OmpW and Ail/OmpX-like might be associated with ceftriaxone-resistance and they are influenced by the regulator gene baeR in S. enterica serovar Typhimurium. The exact function of both OmpW and Ail/OmpX-like in S. enterica serovar Typhimurium remains unknown, except OmpW is the colicin S4 receptor protein in E. coli. These results suggest we could explore the novel gene associated resistance to antibiotics. The similar approach was also applied to study mechanism of antibiotic-resistance in other bacteria, such as Klebsiella pneumoniae, Acinetobacter spp.

Publications

 

  1.    Yi-Chang Liu, I-Hsuan Liu, Wei-Jen Chung, Wensi S. Hu, Wailap Victor Ng, Chi-Yu Lu, Tsung-Yen Huang, Hung-Wei Shu, Kwang-Jen Hsiao, Shih-Feng Tsai, Chuan-Hsiung, Chao-Hsiung Lin. 2012. Proteomics characterization of cytoplasmic and lipid-associated membrane proteins of human pathogen Mycoplasma fermentans M64. PLoS One. 7(4):e35304.   
  2.   Hung-Wei Shu, Tze-Tze Liu, Huang-I Chan, Yen-Ming Liu, Keh-Ming Wu, Hung-Yu Shu, Shih-Feng Tsai, Kwang-Jen Hsiao, Wensi S. Hu*, and Ng WV*. 2012. Complexity of the Mycoplasma fermentans M64 genome and metabolic essentiality and diversity among mycoplasmas. PLoS One. 7(4):e32940. (corresponding author)    
  3.  Hung-Wei Shu, Tze-Tze Liu, Huang-I Chan, Yen-Ming Liu, Keh-Ming Wu, Hung-Yu Shu, Shih-Feng Tsai, Kwang-Jen Hsiao, Wensi S. Hu*, Wailap Victor Ng*. 2011. Genome Sequence of the Repetitive-Sequence-Rich Mycoplasma fermentans Strain M64. J. Bacteriol. 193:4302-4303. (corresponding author)
  4.   Wensi S. Hu*, Hung-Wen Chen, Rui-Yang Zhang, Chung-Yi Huang, Chi-Fan Shen. 2011. The Expression Levels of Outer Membrane Proteins STM1530 and OmpD, Which Are Influenced by the CpxAR and BaeSR Two-Component Systems, Play Important Roles in the Ceftriaxone Resistance of Salmonella enterica Serovar Typhimurium. Antimcrob. Agents Chemother. 55:3829-3837. (corresponding author)
  5.  Guang-Sheng Lei, Wan-Jr Syu, Po-Huang Liang, Kin-Fu Chak, Wensi S. Hu, Shiau-Ting Hu. 2011. Repression of btuB gene transcription in Escherichia coli by the GadX protein. BMC Microbiology 11:33.
  6.  Yen-Chi Yu, Ching-Nan Lin, Shao-Hung Wang, Swee-Chuan Ng, Wensi S. Hu, Wan-Jr Syu. 2010. A putative lytic transglycosylase tightly regulated and critical for the EHEC type three secretion. J. Biomed Sci. 17:52.
  7.   Ya-Chen Liu, Wei-Chih Lai, Kai-An Chuang, Yu-Jie Shen, Wensi S. Hu, Cheng-Han Ho, Yu-Bei Chen, Min-Fen Hsu, Hui-Chi Hsu, Chien-Hui Lieu. 2010. Blockade of JAK2 Activity Suppressed Accumulation of beta-Catenin in Leukemia Cells. J. Cell. Biochem. 111:402-411.
  8.   Wensi S. Hu*, Jing-Fang Lin, Ying-Hsiu Lin, Hsin-Yu Chang. 2009. Outer Membrane Protein STM3031 (Ail/OmpX-Like Protein) Plays a Key Role in the Ceftriaxone Resistance of Salmonella enterica Serovar Typhimurium. Antimcrob. Agents Chemother. 53:3248-3255. (corresponding author)
  9.  Wensi S. Hu*, Shu-Man Yao , Chang-Phone Fung, Yi-Ping Hsieh, Chang-Pan Liu, Jing-Fang Lin. 2007. An OXA-66/OXA-51-Like Carbapenemase and Possibly an Efflux Pump Are Associated with Resistance to Imipenem in Acinetobacter baumannii. Antimcrob. Agents Chemother. 51:3844-3852. (corresponding author)
  10.   Wensi S. Hu*, Yin-Hung Lin, Chun-Chieh Shih. 2007. A proteomic approach to study Salmonella enterica Serovar Typhimurium putative transporter YjeH associated with ceftriaxone resistance. Biochem. Bioph. Res. Co. 361:694-699. (corresponding author)
  11.   Wensi S. Hu*, Pei-Chuan Li, Chao-Yin Cheng. 2005. Correlation between Ceftriaxone Resistance of Salmonella enterica Serovar Typhimurium and Expression of Outer Membrane Proteins OmpW and Ail/OmpX-Like Protein, Which Are Regulated by BaeR of a Two-Component System. Antimcrob. Agents Chemother. 51:3955-3958. (corresponding author)
  12.  Ko-Jiunn Liu, Chun-Ting Chen, Wensi S. Hu, Yi-Mei Hung, Chiung-Yueh Hsu, Bin-Fay Chuang, Shin-Hun Juang. 2004. Expression of cytoplasmic-domain substituted epidermal growth factor receptor inhibits tumorigenicity of EGFR-overexpressed of human glioblastoma multiforme. Intl. J. Oncol. 24:581-590.
  13. Wensi S. Hu*, Chun-Chun Yang. 2001. IS1550 from Mycoplasma fermentans is transposable in Escherichia coli. FEMS Microbiol. Lett. 198:159-164. (corresponding author)
  14.   Wensi S. Hu, Michael M. Hayes, Richard Yuan-Hu Wang, James Wai-Kuo Shih, Shyh-Ching Lo. 1998. High-Frequecy DNA rearrangements in the Chromosomes of Clinically Isolated Mycoplasma fermentans. Current Microbiology. 37:1-5. (first author)