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賴銘志

賴銘志/Ming-Chih Lai

職稱: 副教授

現職: 副教授

信箱: mclai@mail.cgu.edu.tw

電話: 03-2118800#3354

學歷: 國防醫學院生命科學所博士

專長領域: 核酸代謝、癌症研究及分子病毒

工作經歷

2022-迄今  長庚大學生物醫學系 副教授

2014-2022  長庚大學生物醫學系 助理教授

2010-2014  成功大學生理科所 (專案)助理研究員

2008-2010  中央研究院生物醫學所 博士後研究員

研究方向及研究室特色

(一)   研究DEAD-box RNA解旋酶DDX3DDX24的生物功能

人類 DDX3 DDX24 蛋白皆屬於 DEAD-box RNA 解旋酶家族,此類 RNA 解旋酶在真核生物的基因表現與調控中扮演不可或缺的角色。先前,我們發現 DDX3 參與細胞生長與先天免疫(包含發炎反應);最近更證實 DDX3 microRNA 生合成與 RNA 干擾過程中具有關鍵作用,並對卵子及卵巢的發育至關重要。然而,目前仍有若干重要問題尚待釐清:

1.      DDX3 對神經元與腦部發育的影響

2.      DDX3 與神經退化性疾病之可能關聯

另一方面,我們近期的研究顯示,DDX24 可透過調控 HO-1 表現,發揮抗氧化、抗凋亡及抗發炎的功能。關於 DDX24 的作用機制,仍有多項值得深入探討的研究方向:

1.      DDX24 在免疫與發炎反應中的重要性

2.      DDX24 調控 ANKRD1 之機制與功能

3.      DDX24 調控 FERMT1 之機制與功能

(二)      探討大腸癌細胞在缺氧下的轉譯調控機制

大腸直腸癌(colorectal cancer, CRC)是全球最常見的癌症之一。在台灣,CRC 已連續十餘年位居癌症發生率第一名。許多末期CRC患者因治療成效有限,五年內的死亡率依然偏高,因此迫切需要開發新的治療策略與改良療法。缺氧是腫瘤微環境中常見的生理與病理現象,已知能促進腫瘤惡化並與不良預後密切相關。因此,深入探討缺氧所誘導的基因表現變化,可能為癌症治療開啟新的契機。本研究將著重於以下核心問題:

1.      探討缺氧在大腸癌細胞中所誘導之轉譯調控的分子機制

2.      發掘大腸直腸癌的診斷性生物標記與潛在抗癌治療標靶

() 提升中國倉鼠卵巢細胞之重組蛋白生產能力

值得注意的是,目前將近八成經核准使用的人類治療性抗體皆由中國倉鼠卵巢(Chinese hamster ovary, CHO)細胞所生產。為了進一步提升CHO細胞的重組蛋白產量並降低細胞培養成本,我們將運用基因工程技術對CHO細胞株進行改良。


論文與著作

1.      Yu-Xiu Lin, Pei-Yu Hung, Yu-Ting Jiang, Ting-Yi Wu, Hsin-Yuan Hung, Ming-Chih Lai*. (2025 Aug). Anti-apoptotic and anti-oxidative effects of DDX24 through HO-1 transcriptional regulation. FASEB J. 39(16):e70968. doi: 10.1096/fj.202500598RR. (SCIE, 2024 IF=4.2, Ranking 17/107 in BIOLOGY)

2.      Hung-Hsuan Li, Hsin-Yuan Hung, Jau-Song Yu, Yu-Cheng Liao, Ming-Chih Lai*. (2025 Feb). Hypoxia-induced translation of collagen-modifying enzymes PLOD2 and P4HA1 is dependent on RBM4 and eIF4E2 in human colon cancer HCT116 cells. FEBS J. 292(4):881-898. doi: 10.1111/febs.17371. (SCIE, 2024 IF=4.2, Ranking 99/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

3.      Ming-Chih Lai*, Yen-Ling Yu, Chiao-Nung Chen, Jau-Song Yu, Hsin-Yuan Hung, Shih-Peng Chan*. (2025 Jan). DDX3 participates in miRNA biogenesis and RNA interference through translational control of PACT and interaction with AGO2. FEBS Open Bio 15(1):180-195. doi: 10.1002/2211-5463.13920. (SCIE, 2024 IF=2.3, Ranking 234/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

4.      Shang-Yu Tsai, Chih-Hung Lin, Yu-Ting Jiang, Guo-Jen Huang, Haiwei Pi, Hsin-Yuan Hung, Woan-Yuh Tarn, Ming-Chih Lai*. (2024 Nov). DDX3 is critical for female fertility via translational control in oogenesis. Cell Death Discovery 10(1):472. doi: 10.1038/s41420-024-02242-6. (SCIE, 2024 IF=7.0, Ranking 42/204 in CELL BIOLOGY)

5.      Ming-Chih Lai*, Yi-Pin Chen, Ding-An Li, Jau-Song Yu, Hsin-Yuan Hung, Woan-Yuh Tarn* (2022 Feb) DDX3 interacts with USP9X and participates in deubiquitination of the anti-apoptotic protein MCL1. FEBS J. 289(4): 1043-1061. doi: 10.1111/febs.16219. (SCIE, 2024 IF=4.2, Ranking 99/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

6.      Ming-Chih Lai, Han-Hsiang Chen, Peng Xu, Robert YL Wang*. (2020 Jan). Translation control of Enterovirus A71 gene expression. Journal of Biomedical Science 27(1):22. doi: 10.1186/s12929-019-0607-9. (SCIE, 2024 IF=12.1 Ranking 9/195 in MEDICINE, RESEARCH & EXPERIMENTAL)

7.      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 Mar). hnRNPM induces translation switch under hypoxia to promote colon cancer development. EBioMedicine 41: 299-309. doi: 10.1016/j.ebiom.2019.02.059. (SCIE, 2024 IF=10.8, Ranking 13/195 in MEDICINE, RESEARCH & EXPERIMENTAL)

8.      Yu-Chang Ku, Min-Hua Lai, Chen-Chia Lo, Yi-Chuan Cheng, Jian-Tai Qiu, Woan-Yuh Tarn, Ming-Chih Lai*. (2018 Dec). DDX3 participates in translational control of inflammation induced by infections and injuries. Mol. Cell. Biol. 39(1): e00285-18. doi: 10.1128/MCB.00285-18. (SCIE, 2024 IF=2.7, Ranking 197/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

9.      Jeng-Ting Chen, Chien-Chun Liu, Jau-Song Yu, Hung-Hsuan Li, Ming-Chih Lai*. (2018 Sep). Integrated omics profiling identifies hypoxia-regulated genes in HCT116 colon cancer cells. J. Proteomics 188: 139-151. doi: 10.1016/j.jprot.2018.02.031. (SCIE, 2024 IF=2.8, Ranking 38/86 in BIOCHEMICAL RESEARCH METHODS)

10.  Ming-Chih Lai*, Chiao-May Chang, H. Sunny Sun*. (2016 Apr). Hypoxia induces autophagy through translational up-regulation of lysosomal proteins in human colon cancer cells. PLoS One 11(4): e0153627. doi: 10.1371/journal.pone.0153627. (SCIE, 2024 IF=2.6, Ranking 44/135 in MULTIDISCIPLINARY SCIENCES)

11.  Ming-Chih Lai*, H. Sunny Sun, Shainn-Wei Wang, Woan-Yuh Tarn*. (2016 Jan). DDX3 functions in antiviral innate immunity through translational control of PACT. FEBS J. 283(1): 88-101. doi: 10.1111/febs.13553. (SCIE, 2024 IF=4.2, Ranking 99/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

12.  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 Mar). Overexpression of FGF9 incolon cancer cells is mediated by hypoxia-induced translational activation. Nucleic Acids Res. 42(5): 2932-2944. doi: 10.1093/nar/gkt1286. (SCIE, 2024 IF=13.1, Ranking 13/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

13.  Ming-Chih Lai, Shainn-Wei Wang, Lie Cheng, Woan-Yuh Tarn, Shaw-Jenq Tsai*, H. Sunny Sun*. (2013 Jul). Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation. PLoS One 8(7): e68665. doi: 10.1371/journal.pone.0068665. (SCIE, 2024 IF=2.6, Ranking 44/135 in MULTIDISCIPLINARY SCIENCES)

14.  Woan-Yuh Tarn*, Ming-Chih Lai*. (2011 Feb). Translational control of cyclins. Cell Div. 6(1):5. doi: 10.1186/1747-1028-6-5. (SCIE, 2024 IF=2.2, Ranking 158/204 in CELL BIOLOGY)

15.  Ming-Chih Lai, Wen-Cheng Chang, Sheau-Yann Shieh, Woan-Yuh Tarn*. (2010 Nov). DDX3 regulates cell growth through translational control of cyclin E1. Mol. Cell. Biol. 30(22): 5444-5453. doi: 10.1128/MCB.00560-10. (SCIE, 2024 IF=2.7, Ranking 197/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

16.  Ming-Chih Lai, Tsui-Yi Peng, Woan-Yuh Tarn*. (2009 Mar). Functional interplay between viral and cellular SR proteins in control of post-transcriptional gene regulation. FEBS J. 276(6): 1517-1526. doi: 10.1111/j.1742-4658.2009.06894.x. (SCIE, 2024 IF=4.2, Ranking 99/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

17.  Ming-Chih Lai, Yan-Hwa Wu Lee, Woan-Yuh Tarn*. (2008 Sep). 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. doi: 10.1091/mbc.e07-12-1264. (SCIE, 2024 IF=2.7, Ranking 133/204 in CELL BIOLOGY)

18.  Ming-Chih Lai, Woan-Yuh Tarn*. (2004 Jul). Hypophosphorylated ASF/SF2 binds TAP and is present in messenger ribonucleoproteins. J. Biol. Chem. 279: 31745- 31749. doi: 10.1074/jbc.C400173200. (SCIE, 2024 IF=3.9, Ranking 114/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

19.  Ming-Chih Lai, Hao-Wei Kuo, Wen-Cheng Chang, Woan-Yuh Tarn*. (2003 Mar). A novel splicing regulator shares a nuclear import pathway with SR proteins. EMBO J. 22(6): 1359-1369. doi: 10.1093/emboj/cdg126. (SCIE, 2024 IF=8.3, Ranking 30/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

20.  Chin Li, Ru-Inn Lin, Ming-Chih Lai, Pin Ouyang, Woan-Yuh Tarn*. (2003 Oct). 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. doi: 10.1128/MCB.23.20.7363-7376.2003. (SCIE, 2024 IF=2.7, Ranking 197/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

21.  Ming-Chih Lai, Ru-Inn Lin, Woan-Yuh Tarn*. (2003 May). Differential effects of hyperphosphorylation on splicing factor SRp55. Biochem. J. 371(Pt 3): 937-945. doi: 10.1042/BJ20021827. (SCIE, 2024 IF=4.3, Ranking 91/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

22.  Ming-Chih Lai, Ru-Inn Lin, Woan-Yuh Tarn*. (2001 Aug). Transportin-SR2 mediates nuclear import of phosphorylated SR proteins. Proc. Natl. Acad. Sci. USA 98(18): 10154-10159. doi: 10.1073/pnas.181354098. (SCIE, 2024 IF=9.1, Ranking 14/135 in MULTIDISCIPLINARY SCIENCES)

23.  Ming-Chih Lai, Ru-Inn Lin, Shin-Yi Huang, Ching-Wei Tsai, Woan-Yuh Tarn*. (2000 Mar). A human importin-β family protein, transportin-SR2, interacts with the phosphorylated RS domain of SR proteins. J. Biol. Chem. 257(11): 7950-7957. doi: 10.1074/jbc.275.11.7950. (SCIE, 2024 IF=3.9, Ranking 114/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

24.  Ming-Chih Lai, Bee Heong Teh, Woan-Yuh Tarn*. (1999 Apr). 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. doi: 10.1074/jbc.274.17.11832. (SCIE, 2024 IF=3.9, Ranking 114/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

25.  Ming-Chih Lai, Yuung-Chiarng Wang, Feng-Yuan Yang, Lo-Chun Au*. (1997 Sep). Enhancement of transfection efficiency by using oligodeoxyribonucleotide as carrier. Anal. Biochem. 251(2): 292-294. doi: 10.1006/abio.1997.2297. (SCIE, 2024 IF=2.5, Ranking 45/86 in BIOCHEMICAL RESEARCH METHODS)

26.  W. -J. Peng, J. -T. Pan, M. -C. Lai, C. -F. Chiu and T. -H. Lin*. (1997 Oct). The genome of moloney murine leukemia virus can be integrated by the Integrase of human Immunodeficiency virus type 1 expressed alone in vivo. Proc. Natl. Sci. Counc. ROC, Part B: Life Science 21(4): 144-160. (SCI)

27.  C. -Y. Wang, C. -F. Yang, M. -C. Lai, Y. -H. Lee, T. -L. Lee and T. -H. Lin*. (1994 Aug). Molecular dynamics simulation of a leucine zipper motif predicted for the integrase of human immunodeficiency virus type 1. Biopolymers 34(8): 1027-1036. doi: 10.1002/bip.360340806. (SCIE, 2024 IF=3.2, Ranking 151/319 in BIOCHEMISTRY & MOLECULAR BIOLOGY)