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賴銘志(Ming-Chih Lai)

賴銘志 (Ming-Chih Lai)

職稱

副教授

最高學歷

國防醫學院生命科學所 博士

E-mail

mclai@mail.cgu.edu.tw

電話：

+886-3-211-8800 ext.3354

傳真

+886-3-211-8700

實驗室

核酸研究實驗室

專長

核酸代謝、癌症研究及分子病毒

研究方向及研究室特色

(一)探討大腸癌細胞在缺氧環境下的轉譯調控

大腸癌在全世界是很普遍的癌症，目前在國人癌症死因中排名第三(僅次於肺癌及肝癌)，其發生率在過去二十多年仍持續穩定增加，雖然已有許多研究報告讓我們了解大腸癌形成的基因致變過程，然而多數大腸癌末期病人卻常因為治療無效而死亡，其五年存活率仍然不高，所以我們亟需新的策略及更佳的療法來治療大腸癌。 

    細胞缺氧是普遍常見的生理及病理現象，以腫瘤生成為例，由於癌細胞的快速增生及異常的血管新生造成腫瘤內有許多不同程度的缺氧區域，癌細胞必須藉由改變基因表現來適應缺氧環境的壓力，缺氧在腫瘤惡性化過程中也扮演著重要角色，腫瘤內的缺氧細胞也是造成臨床上預後不良的主要原因，先前的研究顯示經過缺氧處理的癌細胞對於放射治療及許多常用的化學治療藥劑有較強的抵抗能力，因此，深入了解缺氧所導致基因表現的變化，可能開啟未來在癌症治療上的新視野。

    目前我們的研究方向如下：

(1) 鑑定大腸癌細胞在缺氧環境下所調控的基因

(2) 探討大腸癌細胞在缺氧下進行轉譯調控的分子機制

(3) 鑑定大腸癌細胞在缺氧環境下所活化的ITAFs因子

(4) 找尋大腸癌的診斷生物標記及抗癌標的分子

(二) 研究DEAD-box RNA解旋酶DDX3的生物功能

    人類DDX3蛋白是屬於DEAD-box RNA解旋酶家族的成員之一，此類RNA解旋酶在真核生物的基因表現上扮演不可或缺的角色，DDX3及其同源蛋白已經被證明參與mRNA代謝的許多過程，包括轉譯初期。我們之前的研究發現：細胞在壓力的環境下，DDX3會集中到細胞質的壓力體(SGs)，這也暗示DDX3在轉譯初期上的角色。DDX3對於一般mRNA的轉譯似乎並非必要，但它可以協助具有較長及二級結構5' UTR的特定mRNA轉譯。考量DDX3在執行轉譯功能時需要其RNA解旋酶活性，所以我們認為DDX3在轉譯初期可能是藉由解開特定mRNA的5' UTR二級結構來協助核糖體掃描。

    未來我們將研究DDX3所媒介的轉譯調控在生物功能上的重要性，目前還有許多尚未解答的問題如下：

(1) DDX3在先天免疫反應中所扮演的真實角色

(2) DDX3對於microRNA熟成的重要性

(3) DDX3在生殖細胞發育過程中所扮演的關鍵角色

(4) DDX3的後轉譯修飾對其功能的影響及調控

論文與著作

Publications:

  1. Tsung-Ming Chen, Ming-Chih Lai, Yi-Han Li, Ya-Ling Chan, Chih-Hao Wu, Yu-Ming Wang, Chun-Wei Chien, San-Yuan Huang, H. Sunny Sun*, Shaw-Jenq Tsai*. (2019). hnRNPM induces translation switch under hypoxia to promote colon cancer development. EBioMedicine doi: 10.1016/j.ebiom.2019.02.059 (SCI, 2017 IF=6.183, Ranking 13/133 in MEDICINE, RESEARCH & EXPERIMENTAL)
  2. Yu-Chang Ku, Min-Hua Lai, Chen-Chia Lo, Yi-Chuan Cheng, Jian-Tai Qiu, Woan-Yuh Tarn, Ming-Chih Lai*. (2019). DDX3 participates in translational control of inflammation induced by infections and injuries. Mol. Cell. Biol. 39(1): e00285-18 (SCI, 2017 IF=3.813, Ranking 85/293 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  3. Jeng-Ting Chen, Chien-Chun Liu, Jau-Song Yu, Hung-Hsuan Li, Ming-Chih Lai*. (2018). Integrated omics profiling identifies hypoxia-regulated genes in HCT116 colon cancer cells. J. Proteomics 188: 139-151 (SCI, 2017 IF=3.722, Ranking 17/79 in BIOCHEMICAL RESEARCH METHODS)
  4. Ming-Chih Lai*, Chiao-May Chang, H. Sunny Sun*. (2016). Hypoxia induces autophagy through translational up-regulation of lysosomal proteins in human colon cancer cells. PLOS ONE 11(4): e0153627 (SCI, 2017 IF=2.766, Ranking 15/64 in MULTIDISCIPLINARY SCIENCES)
  5. Ming-Chih Lai*, H. Sunny Sun, Shainn-Wei Wang, Woan-Yuh Tarn*. (2016). DDX3 functions in antiviral innate immunity through translational control of PACT.
    FEBS J. 283(1): 88-101 (SCI, 2017 IF=4.530, Ranking 58/293 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  6. Tsung-Ming Chen, Yu-Heng Shih, Joseph T. Tseng, Ming-Chih Lai, Chih-Hao Wu, Yi-Han Li, Shaw-Jenq Tsai*, H. Sunny Sun*. (2014). Overexpression of FGF9 in colon cancer cells is mediated by hypoxia-induced translational activation. Nucleic Acids Res. 42(5): 2932-2944 (SCI, 2017 IF=11.561, Ranking 10/293 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  7. Ming-Chih Lai, Shainn-Wei Wang, Lie Cheng, Woan-Yuh Tarn, Shaw-Jenq Tsai*, H. Sunny Sun*. (2013). Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation. PLOS ONE 8(7): e68665 (SCI, 2017 IF=2.766, Ranking 15/64 in MULTIDISCIPLINARY SCIENCES)
  8. Woan-Yuh Tarn*, Ming-Chih Lai*. (2011). Translational control of cyclins. Cell Div. 6(1):5 (SCI, 2017 IF=4.684, Ranking 57/190 in CELL BIOLOGY)
  9. Ming-Chih Lai, Wen-Cheng Chang, Sheau-Yann Shieh, Woan-Yuh Tarn*. (2010). DDX3 regulates cell growth through translational control of cyclin E1.
    Mol. Cell. Biol. 30(22): 5444-5453 (SCI, 2017 IF=3.813, Ranking 85/293 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  10. Ming-Chih Lai, Tsui-Yi Peng, Woan-Yuh Tarn*. (2009). Functional interplay between viral and cellular SR proteins in control of post-transcriptional gene regulation. FEBS J. 276(6): 1517-1526 (SCI, 2017 IF=4.530, Ranking 58/293 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  11. Ming-Chih Lai, Yan-Hwa Wu Lee, Woan-Yuh Tarn*. (2008). The DEAD-box RNA helicase DDX3 associates with export messenger ribonucleoproteins as well as tip-associated protein and participates in translational control. Mol. Biol. Cell 19(9): 3847-3858 (SCI, 2017 IF=3.512, Ranking 87/190 in CELL BIOLOGY)
  12. Ming-Chih Lai, Woan-Yuh Tarn*. (2004). Hypophosphorylated ASF/SF2 binds TAP and is present in messenger ribonucleoproteins. J. Biol. Chem. 279: 31745- 31749 (SCI, 2017 IF=4.010, Ranking 75/293 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  13. Ming-Chih Lai, Hao-Wei Kuo, Wen-Cheng Chang, Woan-Yuh Tarn*. (2003). A novel splicing regulator shares a nuclear import pathway with SR proteins.
    EMBO J. 22(6): 1359-1369 (SCI, 2017 IF=10.557, Ranking 13/293 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  14. Chin Li, Ru-Inn Lin, Ming-Chih Lai, Pin Ouyang, Woan-Yuh Tarn*. (2003). Nuclear Pnn/DRS protein binds to spliced mRNPs and participates in mRNA processing and export via interaction with RNPS1. Mol. Cell. Biol. 23(20): 7363-7376 (SCI, 2017 IF=3.813, Ranking 85/293 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  15. Ming-Chih Lai, Ru-Inn Lin, Woan-Yuh Tarn*. (2003). Differential effects of hyperphosphorylation on splicing factor SRp55. Biochem. J. 371(Pt 3): 937-945 (SCI, 2017 IF=3.857, Ranking 81/293 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  16. Ming-Chih Lai, Ru-Inn Lin, Woan-Yuh Tarn*. (2001). Transportin-SR2 mediates nuclear import of phosphorylated SR proteins. Proc. Natl. Acad. Sci. USA 98(18): 10154-10159 (SCI, 2017 IF=9.504, Ranking 5/64 in MULTIDISCIPLINARY SCIENCES)
  17. Ming-Chih Lai, Ru-Inn Lin, Shin-Yi Huang, Ching-Wei Tsai, Woan-Yuh Tarn*. (2000). A human importin-β family protein, transportin-SR2, interacts with the phosphorylated RS domain of SR proteins. J. Biol. Chem. 257(11): 7950-7957 (SCI, 2017 IF=4.010, Ranking 75/292 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  18. Ming-Chih Lai, Bee Heong Teh, Woan-Yuh Tarn*. (1999). A human papillomavirus E2 transcriptional activator. The interactions with cellular splicing factors and potential function in pre-mRNA processing. J. Biol. Chem. 274(17): 11832-11841 (SCI, 2017 IF=4.010, Ranking 75/293 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  19. Ming-Chih Lai, Yuung-Chiarng Wang, Feng-Yuan Yang, Lo-Chun Au*. (1997). Enhancement of transfection efficiency by using oligodeoxyribonucleotide as carrier. Anal. Biochem. 251(2): 292-294 (SCI, 2017 IF=2.275, Ranking 42/79 in BIOCHEMICAL RESEARCH METHODS)