Tzu-Hao Cheng
Basic Neuroscience
Name Tzu-Hao Cheng
Office Tel No. 886-2-28267331
EDUCATION/TRAINING PhD, Pharmacology, Rutgers University/UMDNJ, USA ; Post-doc, Genetics, Stanford University, USA
Research Supt4h on Huntington's disease and other polyQ-mediated neurodegenerative disorders
研究概況 研究領域--1.CAG三核苷酸擴張序列對轉錄作用之影響
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.
Year Paper Title
2017 PC Tsai, BW Soong, I Mademan, YH Huang, CR Liu, CT Hsiao, HT Wu, TT Liu, YT Liu, YT Tseng, KP Lin, UC Yang, KW Chung, BO Choi, GA Nicholson, ML Kennerson, CC Chan, PD Jonghe, TH Cheng, YC Liao*, S Züchner, J Baets, and YC Lee*. (2017). A recurrent WARS mutation is a novel cause of autosomal dominant distal hereditary motor neuropathy. Brain (in press) .
2016 NJ Kramer, Y Carlomagno, YJ Zhang, S Almeida, CN Cook, TF Gendron, M Prudencio, MV Blitterswijk, V Belzil, J Couthouis, JW Paul III, LD Goodman, L Daughrity, J Chew, A Garrett, L Pregent, K Jansen-West, LJ Tabassian, R Rademakers, K Boylan, NR Graff-Radford, KA Josephs, JE Parisi, DS Knopman, RC Petersen, BF Boeve, N Deng, Y Feng, TH Cheng, DW Dickson, SN Cohen, NM Bonini, CD Link, FB Gao, L Petrucelli*, AD Gitler*. (2016). Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts. Science 353, 708-712.
2016 SY Chen, SC Teng, TH Cheng*, KJ Wu*. (2016). miR-1236 regulates hypoxia-induced epithelial-mesenchymal transition and cell migration/invasion through repressing SENP1 and HDAC3. Cancer Letters 378, 59-67.
2015 CR Liu and TH Cheng*. (2015). Allele-selective Suppression of Mutant Genes in Polyglutamine Diseases. Journal of neurogenetics 29 (2-3): 41-49.
2015 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.
2015 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.
2013 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.
2013 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.
2012 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
2011 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.
2011 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
2010 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
2009 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.
2009 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.
2007 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.
2007 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.
2006 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.
2001 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.
2000 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.
2000 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.
1999 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.
1998 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.