生物科技產業碩-博士學位學程

研究主題

(一)   研究DEAD-box RNA解旋酶DDX3的生物功能

人類DDX3蛋白是DEAD-box RNA解旋酶家族成員之一，這些RNA解旋酶在真核生物的基因表現與調控扮演不可或缺的角色。先前，我們證明DDX3對於具有較長及二級結構5’ UTR的特定mRNA轉譯至關重要。因為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可能在轉譯初期藉由解開特定mRNA的5’ UTR二級結構來促進核糖體掃描。研究DDX3介導轉譯調控的生物功能非常有趣。然而，目前還有一些尚未清楚解答的問題如下：

(1)   DDX3在microRNA生合成及RNA干擾所扮演的角色

(2)   DDX3在卵子發生和女性生育能力中的重要性

(3)   DDX3對於神經元和腦部發育的影響

(4)   DDX3可能與神經退化性疾病有關

(二)   探討大腸癌細胞在缺氧下的轉譯調控機制

大腸直腸癌（CRC）是全球最常見的癌症之一。在台灣，大腸直腸癌已連續15年位居癌症發生率首位。許多大腸直腸癌末期患者常因治療無效而在五年內死亡。因此，亟需新的策略和改進的療法來治療大腸直腸癌。缺氧是普遍常見的生理及病理現象，包括腫瘤生成。缺氧可能促進腫瘤惡化並與預後不良有關。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。我們目前的研究主要集中在以下問題：

(1)   在大腸癌細胞中研究缺氧誘導轉譯的分子機制

(2)   鑑定在缺氧下活化特定mRNA轉譯的RNA結合蛋白

(3)   尋找大腸直腸癌的診斷生物標記和潛在的抗癌標靶

(三)   提高中國倉鼠卵巢細胞生產重組蛋白的能力

值得注意的是，將近八成核准使用的人類治療抗體是由中國倉鼠卵巢(CHO)細胞所產生。為了提高CHO細胞重組蛋白的產量並且降低細胞培養成本，我們計劃利用基因工程技術來改良CHO細胞株。

發表著作

1.      Hung-Hsuan Li, Hsin-Yuan Hung, Jau-Song Yu, Ming-Chih Lai*. (2024 Dec). Hypoxia-induced translation of collagen-modifying enzymes PLOD2 and P4HA1 is dependent on RBM4 and eIF4E2 in human colon cancer HCT116 cells. FEBS J. (SCI, 2023 IF= 5.5, Ranking 58/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

2.      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. (SCI, 2023 IF= 6.1, Ranking 49/205 in CELL BIOLOGY)

3.      Ming-Chih Lai^*, Yen-Ling Yu, Chiao-Nung Chen, Jau-Song Yu, Hsin-Yuan Hung, Shih-Peng Chan^*. (2024 Nov). DDX3 participates in miRNA biogenesis and RNA interference through translational control of PACT and interaction with AGO2. FEBS Open Bio doi: 10.1002/2211-5463.13920. (SCI, 2023 IF= 2.8, Ranking 184/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

4.      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. (SCI, 2023 IF= 5.5, Ranking 58/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

5.      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. (SCI, 2023 IF= 9.0 Ranking 30/205 in CELL BIOLOGY)

6.      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. (SCI, 2023 IF= 9.7, Ranking 12/189 in MEDICINE, RESEARCH & EXPERIMENTAL)

7.      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. (SCI, 2023 IF= 3.2, Ranking 155/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

8.      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. (SCI, 2023 IF= 2.8, Ranking 35/85 in BIOCHEMICAL RESEARCH METHODS)

9.      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. (SCI, 2023 IF= 2.9, Ranking 31/134 in MULTIDISCIPLINARY SCIENCES)

10.  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. (SCI, 2023 IF= 5.5, Ranking 58/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

11.  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. (SCI, 2023 IF= 16.6, Ranking 6/313 in BIOCHEMISTRY & MOLECULAR BIOLOGY)

榮譽事項

1. 第十六屆細胞及分子生物新知研討會 壁報論文獎
2. 第一屆永信李天德醫藥科技獎--傑出論文獎 & 董事長特別獎
3. 八十九學年度國科會研究獎勵(乙種)
4. 八十八學年度國科會研究獎勵(乙種)