專長
基因轉錄調控、 腦神經退化性疾病、 生化及分子遺傳學分析、小分子藥物開發
辦公室
生物醫學大樓 七樓 R712 室
電話
886-2-2826-7331
Email
thcheng@nycu.edu.tw
ORCiD
0000-0003-2329-7356
經歷
2022-2022
2021迄今
2021-2021
2019 迄今
2019-2021
2018-2019
2017-2019
2017-2017
2017 迄今
2016-2017
2015-2016
2012-2017
2010-2012
2003-2010
2000-2003
國立陽明交通大學 研發長
國立陽明交通大學 副校長
國立陽明交通大學 校區副研發長
國立陽明交通大學 生化暨分子生物研究所 所長
國立陽明大學 副研發長
美國史丹福大學 遺傳學系 客座教授
美國Nuredis Inc., 研究部門負責人
美國Nuredis Inc., 資深訪問學者
國立陽明大學 生化暨分子生物研究所 特聘教授
國立陽明大學 生化暨分子生物研究所 所長
國立陽明大學 生化暨分子生物研究所 代理所長
國立陽明大學 生化暨分子生物研究所 教授
國立陽明大學 生化暨分子生物研究所 副教授
國立陽明大學 生化暨分子生物研究所 助理教授
美國史丹福大學 遺傳學系 博士後研究員
榮譽
2018
2017
09/01/2013-08/31/2017
02/15/2013-11/30/2014
國立陽明大學 傑出校友獎
科技部 傑出研究獎
美國國家衛生研究院 科研計畫補助
美國CHDI基金會 科研計畫補助
研究方向
多種遺傳性腦神經退化性疾病已知是由染色體上某一特定基因之核苷酸重複序列異常擴增所造成，如亨氏舞蹈症、小腦萎縮症、家族性的漸凍人症等。這些致病基因所產生的RNA或是蛋白質對於腦神經細胞具有傷害性，進而造成疾病病徵的產生;但是這些病徵及病理現象可以藉由降低致病基因的表達來減緩甚至停滯疾病的惡化。在我們先前的研究中發現，轉錄延伸因子SUPT4H(酵母菌Spt4的同源基因)對於這些帶有高度核苷酸重複序列的基因表達扮演重要的調控角色。當我們將細胞中或是小鼠的SUPT4H以基因剃除或是SiRNA基因調降時，致病基因表達隨之降低，同時致病基因所產生的病理現象及疾病病徵都能顯著地改善，顯示SUPT4H具有成為核苷酸擴增疾病之藥物開發標的的潛力。
我們實驗室運用多種不同類型的生物模式系統來探討SUPT4H相關的科學議題，如酵母菌、果蠅、人類誘導幹細胞以及小鼠。目前進行中的研究議題為:
- 探討SUPT4H在核苷酸擴增所造成的腦神經退化性疾病之角色以及其在疾病治療之應用。
- 探討SUPT4H對於小鼠腦神經細胞發育以及成鼠腦神經功能的作用。
- 探討SUPT4H對於轉錄作用所誘導之基因體不穩定性的影響。
Multiple inherited neurodegenerative disorders are caused by an abnormal expansion of nucleotide repetitive sequences in the affected genes, including Huntington’s disease (HD), Spinocerebellar ataxia (SCA), and familial amyotrophic lateral sclerosis (ALS). The transcripts and/or translated protein products from this class of disease genes are detrimental to neurons, and the progression of disease phenotypes can be delayed or even reversed by attenuating the expression of disease genes. In our early studies, we identified and characterized SUPT4H (the human homologue of yeast Spt4) as a transcription elongation factor that is required for the expression of genes containing lengthy nucleotide repeats. Through either SUPT4H genetic knock-out or siRNA-mediated knock-down approach, we demonstrated that the phenotypic phenotypes as well as pathological hallmarks associated with disease genes are greatly improved in cell culture and animal models, suggesting SUPT4H is a potential therapeutic target against human nucleotide expansion disorders.
A variety of model organisms, including Yeast, Drosophila, human iPSC, and mouse, are currently employed in the laboratory to address SUPT4H-related scientific subjects. On-going projects are
- Exploring the role of SUPT4H and its application in nucleotide expansion neurological disorders
- Investigating the role of SUPT4H in neural development and brain function using mouse as a model organism.
- Evaluating the effect of SUPT4H on transcription-induced genome instability
研究著作
CC Liu, HR Chan, GC Su, YZ Hsieh, KH Lei, T Kato, TY Yu, YW Kao, TH Cheng, P Chi*, JJ Lin*. (2023). Flap endonuclease Rad27 cleaves the RNA of R-loop structure to suppress telomere recombination. Nucleic Acids Research 51(9):4398-4414.
N Deng, YY Wu, Y Feng, WC Hsieh, JS Song, YS Lin, YH Tseng, WJ Liao, YF Chu, YC Liu, EC Chang, CR Liu, SY Sheu, MT Su, HC Kuo, SN Cohen*, TH Cheng*. (2022). Chemical interference with DSIF complex formation lowers synthesis of mutant huntingtin gene products and curtails mutant phenotypes. Proc Natl Acad Sci U S A 119 (32): e2204779119.
N Deng, Y Zhang, Z Ma, R Lin, TH Cheng, H Tang, MP Snyder, and SN Cohen*. (2022). DSIF modulates RNA polymerase II occupancy according to template G+C content. NAR Genomics and Bioinformatics 4 (3): lqac054.
YH Lee, YS Tsai, CC Chang, CC Ho, HM Shih, HM Chen, HL Lai, CW Lee, YC Lee, YC Liao, UC Yang*, TH Cheng*, YJ Chern*, BW Soong*. (2022). A PIAS1 protective variant S510G delays polyQ disease onset by modifying protein homeostasis. Movement Disorders 37 (4), 767-777.
YC Chen, TH Cheng, WL Lin, CL Chen, WY Yang, C Blackstone, CR Chang*. (2019). Srv2 is a pro-fission factor that modulates yeast mitochondrial morphology and respiration by regulating actin assembly. iScience 11, 305-317.
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 140, 1252-1266.
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.
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.
YW Liu, WK Ong, YW Su, CC Hsu, TH Cheng*, YC Tsai*. (2016).Anti-inflammatory effects of Lactobacillus brevis K65 on RAW 264.7 cells and in mice with dextran sulphate sodium-induced ulcerative colitis. Beneficial Microbes 7, 387-96
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, 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.
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.
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.