生化暨分子生物學科

研究方向及研究室特色

研究方向及研究室特色：
在細胞中，基因表達仰賴嚴謹的轉錄調控。此過程由 Mediator 複合體、RNA 聚合酶 II 及多種轉錄相關複合體等巨分子機器共同協調，確保轉錄能夠精準執行並維持細胞正常運作。一旦這些複合體出現結構或功能異常，便可能導致癌症與其他疾病。然而，這些生物大分子不僅結構高度複雜，亦展現多樣的構型，其精細的調控機制至今仍有許多未解之處。深入理解其分子運作原理，對於疾病研究與治療策略的發展至關重要。

本實驗室專注於真核基因轉錄調控研究，特別聚焦於 Mediator 複合體及其激酶模組的結構與功能，並探討其與多種轉錄因子及細胞訊號傳遞因子的交互作用，以揭示轉錄調控的分子機制。我們運用多種實驗技術，包括單顆粒冷凍電子顯微鏡 (cryo-EM)、X 光晶體學、生化與生物物理方法，以及 AI 輔助的計算建模，來研究這些複合體的結構與調控機制。

研究範疇涵蓋：

• 蛋白質與核酸的交互作用
• 蛋白質構型變化與功能調控
• 巨分子複合體的組裝機制
• 疾病相關突變對蛋白質結構與功能的影響
• 蛋白質與小分子藥物的作用模式

我們以結構生物學為核心，深入解析疾病機制，並透過跨領域與臨床合作，連結基礎研究與癌症治療，為精準醫學探索更多可能。

獲獎 AWARD

1. CPRIT BIG-TCR Annual Retreat, Poster Session – First Prize, Postgraduate group (2024)

2. Department of Biochemistry and Molecular Biology Annual Retreat (McGovern Medical School) – First Place, Poster Presentation (2024)

3. CPRIT BIG-TCR Postdoctoral Research Fellowship – funded by the Cancer Prevention and Research Institute of Texas (2023–2024)

4. Department of Biochemistry and Molecular Biology Annual Retreat (McGovern Medical School) – Third Place, Oral Presentation (2023)

5. Department of Biochemistry and Molecular Biology Annual Retreat (McGovern Medical School) – First Place, Oral Presentation (2022)

6. Distinguished Thesis Prize, 15th TienTe Lee Biomedical Award (2019)
    第十五屆永信李天德醫藥科技獎 — 傑出論文獎

7. Outstanding Award for Postgraduate Students’ Publications, National Taiwan University College of Medicine (2019)
    國立臺灣大學醫學院研究生優秀著作獎 — 107學年度博士班傑出著作獎

8. The 23rd NSRRC (National Synchrotron Radiation Research Center) Users’ Meeting and Workshops – First Place, Student Oral Presentation in Biological Science (2017)

最近五年所發表論文

1. Ti-Chun Chao†, Shin-Fu Chen†, Hee Jong Kim, Hui-Chi Tang, Hsiang-Ching Tseng, An Xu, Leon Palao 3rd, Subash Khadka, Tao Li, Mo-Fan Huang, Dung-Fang Lee, Kenji Murakami#, Thomas G Boyer#, Kuang-Lei Tsai# (2024) Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module. Mol Cell.  84(20), 3932–3949.e10 (†co first author)

2. Ko-Ting Liu, Shin-Fu Chen, Nei-Li Chan (2024) Structural insights into the assembly of type IIA topoisomerase DNA cleavage-religation center. Nucleic Acids Res., gkae657.

3. Jose J Gorbea Colón†, Leon Palao III†, Shin-Fu Chen, Hee Jong Kim, Laura Snyder, Yi-Wei Chang#, Kuang-Lei Tsai#, Kenji Murakami# (2023) Structural basis of a transcription pre-initiation complex on a divergent promoter.  Mol Cell.  83(4):574-588.e11. (†co first author)

4. Lindsey Barron, Subash Khadka, Robert Schenken, Long He, John Blenis, Julian Blagg, Shin-Fu Chen, Kuang-Lei Tsai, Thomas G Boyer. (2021) Identification and characterization of the mediator kinase-dependent myometrial stem cell phosphoproteome.  F&S Science. Volume 2, Issue 4, Pages 383-395

5. Feng Xiong†, Ruoyu Wang†, Joo-Hyung Lee, Shenglan Li, Shin-Fu Chen, Zian Liao, Lana Al Hasani, Phuoc T Nguyen, Xiaoyu Zhu, Joanna Krakowiak, Dung-Fang Lee, Leng Han, Kuang-Lei Tsai, Ying Liu, Wenbo Li. (2021) RNA m6A modification orchestrates a LINE-1–host interaction that facilitates retrotransposition and contributes to long gene vulnerability. Cell Res. 31(8):861-885. (†co first author)

6. Yi-Chuan Li†, Ti-Chun Chao†, Hee Jong Kim, Timothy Cholko, Shin-Fu Chen, Guojie Li, Laura Snyder, Kotaro Nakanishi, Chia-en Chang, Kenji Murakami, Benjamin A Garcia, Thomas G Boyer#, Kuang-Lei Tsai#. (2021) Structure and noncanonical Cdk8 activation mechanism within an Argonaute-containing Mediator kinase module. Sci Adv. 7(3):eabd4484.