Graduate Institute of Biomedical Sciences

Research interests

Gene expression in eukaryotic cells relies on rigorous transcriptional regulation. This process is orchestrated by large macromolecular machines—including the Mediator complex, RNA polymerase II, and other transcription-related complexes

—which ensure accurate transcription and maintain normal cellular function. Structural or functional abnormalities in these complexes can lead to cancer and other diseases. Yet, these biomolecules are not only structurally complex but also adopt diverse conformations, and their fine regulatory mechanisms remain incompletely understood. Elucidating their molecular mechanisms is therefore essential for advancing disease research and developing therapeutic strategies.

Our laboratory focuses on transcriptional regulation in eukaryotes, with a particular emphasis on the structural and functional studies of the Mediator complex and its kinase module. We further investigate their interactions with diverse transcription factors and cellular signaling molecules to uncover the molecular mechanisms underlying transcriptional regulation. We utilize a variety of experimental techniques, including single-particle cryo-electron microscopy (cryo-EM), X-ray crystallography, biochemical and biophysical approaches, and AI-assisted computational modeling, to investigate the structures and regulatory mechanisms of these complexes.

Our research encompasses:

• Protein–nucleic acid interactions
• Protein conformational dynamics
• Assembly mechanisms of macromolecular complexes
• Structural and functional impacts of disease-related mutations
• Protein–small molecule interactions

Grounded in structural biology, we aim to elucidate disease-related mechanisms and, through interdisciplinary and clinical collaborations, bridge fundamental discoveries with cancer therapy, opening new avenues for precision medicine.

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)

7. Outstanding Award for Postgraduate Students’ Publications, National Taiwan University College of Medicine (2019)

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

Publications (Recent 5 years)

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.