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Cheng, Tzu-Hao
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  • Professor & Director
  • Education : PhD, Pharmacology, Rutgers University/UMDNJ, USA ; Post-doc, Genetics, Stanford University, USA
  • Office : R712, 7F, Tradition Medicine Building
  • Phone : 886-2-28267331
  • Email : thcheng@ym.edu.tw
Research--Translational control of mdm2 by eIF4E, Genetic approach to identify the suppressors of polyQ aggregation and explore their potential in the treatment of Huntington's disease

Huntington’s disease (HD) and multiple neurodegenerative disorders are caused by CAG tri-nucleotide expansion. In our earlier published investigation, we showed that the yeast transcription elongation factor Spt4 modulates the expression of genes containing expanded CAG repeats, while having marginal effects on the one with short or no CAG repeats. Lowering SUPT4H (which is homolog of yeast Spt4 in mammalian cells) can selectively reduce the mutant huntingtin gene expression, ameliorate polyQ-mediated protein aggregation, and rescue cells from the deleterious effect of CAG expansion genes in murine striatal neurons. Additional animal studies also reveal that reduction of SUPT4H in mouse brains is associated with decreased HTT protein aggregation, prolonged lifespan, and delay of the motor impairment that normally develops in HD mouse model of R6/2.

We currently are aimed to further understand the functional aspects of SUPT4H in transcription of CAG-expanded DNA template and to assess the suitability of SUPT4H as a therapeutic target against HD and other CAG expansion diseases.

Publications

CR Liu and TH Cheng*. (2015). Allele-selective Suppression of Mutant Genes in Polyglutamine Diseases. Journal of neurogenetics 29 (2-3): 41-49.

 

HM Cheng, Y Chern, CS Lin, SH Li, IH Chen, CR Liu, S Chun, F Rigo, CF Bennett, N Deng, Y Feng, YT Yan*, SN Cohen*, and TH Cheng*. (2015). Effects on Murine Behavior and Lifespan by Selectively Decreasing Expression of Mutant Huntingtin Allele by Supt4h knockdown. PLoS Genetics 11, e1005043.

 

HS Hsu, MH Lin, YH Jang, TT Kuo, CC Liu, and TH Cheng*. (2015). The 4E-BP1/eIF4E ratio is a determinant for rapamycin response in esophageal cancer cells. Journal of Thoracic and Cardiovascular Surgery 149, 378-385.

 

YS Lin, YJ Chen, SN Cohen, and TH Cheng*. (2013). Identification of TSG101 functional domains and p21 loci required for TSG101-mediated p21 gene regulation. PLoS One 8, e79674.

 

YS Lin,TH Cheng,CP Chang, HM Chen, and Y Chern*. (2013). Enhancement of brain-type creatine kinase activity ameliorates neuronal deficits in Huntington's disease. Biochim Biophys Acta. 1832, 742-753.

 

CR Liu, CR Chang, Y Chern, TH Wang, WC Hsieh, WC Shen, CY Chang, IC Chu, N Deng, SN Cohen*, and TH Cheng*. (2012). Spt4 is Selectively Required for Transcription of Extended Trinucleotide Repeats. Cell 148, 690-701.

 

YT Lin, Y Chern, CK Shen, HL Wen, YC Chang, H Li, TH Cheng, HM Hsieh-Li. (2011). Human Mesenchymal Stem Cells Prolong Survival and Ameliorate Motor Deficit through Trophic Support in Huntington's Disease Mouse Models. PLoS One 6, e22924.

 

HS Hsu, HW Chen, CL Kao, ML Wu, Anna FY Li, and TH Cheng*. (2011). MDM2 is overexpressed and regulated by the eukaryotic translation initiation factor 4E (eIF4E) in human squamous cell carcinoma of esophagus. Annals of Surgical Oncology 18, 1469-1477.

 

V Ghukasyan, CC Hsu, CR Liu, FJ Kao and TH Cheng*. (2010). Fluorescence lifetime dynamics of eGFP in protein aggregates with expanded polyQ. Journal of Biomedical Optics 15, 016008.

 

CL Kao, HS Hsu, HW Chen, and TH Cheng*. (2009). Rapamycin increases the p53/MDM2 protein ratio and p53-dependent apoptosis by translational inhibition of mdm2 in cancer cells. Cancer Letters 286, 250-259.

 

TH Cheng, PK Hsu, Anna FY Li, IC Hung, MH Huang, and HS Hsu. (2009). Correlation of p53, MDM2 and p14ARF protein expression in Human Esophageal Squamous Cell Carcinoma. Journal of Cancer Research and Clinical Oncology 135, 1577-1582.

 

HH Chua, HH Lee, SS Chang, CC Lu, TH Yeh, TY Hsu, TH Cheng, JT Cheng, MR Chen, and CH Tsai. (2007). Role of TSG101 in Epstein-Barr viral late gene transcription. Journal of Virology 81, 2459-2471.

 

TH Cheng and SN Cohen. (2007). Human MDM2 isoforms translated differentially on constitutive versus p53-regulated transcripts have distinct functions in the p53/MDM2 and TSG101/MDM2 feedback control loops. Molecular and Cellular Biology 27, 111-119.

 

SH Chao, TH Cheng, CY Shaw, MH Lee, YH Hsu, and YC Tsai. (2006). Characterization of a Novel PepF-Like Oligopeptidase Secreted by Bacillus amyloliquefaciens 23-7A. Applied and Environmental Microbiology 72, 23-27.

 

Yao-Cheng Li, Tzu-Hao Cheng, and Marc R. Gartenberg. (2001). Establishment of transcriptional silencing in the absence of DNA replication. Science 291, 650-653.

 

Tzu-Hao Cheng and Marc R. Gartenberg. (2000). Yeast silent chromatin is a dynamic structure that requires silencers continuously. Genes and Development 14, 452-463.

 

Tzu-Hao Cheng, Chuang-Rung Chang, Prabha Joy, Svetlana Yablok, and Marc R. Gartenberg. (2000). Controlling gene expression in yeast by inducible site-specific recombination. Nucleic Acids Research e28.

 

Athar Ansari, Tzu-Hao Cheng, Marc.R. Gartenberg. (1999). Isolation of chromatin rings from yeast employing site-specific recombination in vivo. Methods 17, 104-111.

 

Tzu-Hao Cheng, Yao-Cheng Li, and Marc R. Gartenberg. (1998). Persistence of an alternate chromatin structure at silenced loci in the absence of silencers. Proc Natl Acad Sci U S A 95, 5521-5526.

 

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