• DNA Damage Response and Repair
• Assembly and Regulation of Multicomponent Macromolecular Complexes
• Integrative Biophysics, Biochemistry and Structural Biology
• Cryo-Electron Microscopy
• Structure-Based Drug Discovery

Dr Shikang Liang is currently an Assistant Professor in the School of Biomedical Science at the University of Hong Kong. He earned his BSc degree in Biotechnology from Fudan University. During his undergraduate, he joined the joint-undergraduate programme and earned BSc degree in Biochemistry with Honours Class I from University of Birmingham. He was also awarded a one-year exchange scholarship at University of California, Berkeley.

Dr Liang later earned his PhD degree in Biochemistry from the University of Cambridge and decided to continue his postdoctoral training at Cambridge. Since he started his PhD research in the lab of Professor Sir Tom Blundell in 2015, he has been focusing on structural and molecular investigation targeting human DNA damage response and repair. In 2023, he joined the University of Hong Kong as an Assistant Professor.

DNA is the main carrier of human genetic information. It must be delivered undamaged to the next generation to sustain inheritance and health. However, DNA damage is inevitable due to various exogenous and endogenous factors. A single human cell experiences tens of thousands of DNA lesions every day.

To avoid genome instability, relevant DNA damage response and repair (DDR&R) pathways cooperates in a timely and accurate manner. DDR&R is fundamental in genome stability and has exhibited high relevance to different diseases including cancer, immunodeficiency, and neurodegeneration. Drug discovery targeting human DDR&R has also been proved successful and promising in cancer treatment.

The Liang lab is interested in understanding the assembly and regulation of key multicomponent macromolecular complexes regulating DDR&R (e.g., DNA-dependent protein kinase and complexes), using state-of-the-art integrative biochemical, biophysical, and structural methods including cryo-electron microscopy (cryo-EM), and exploring how better molecular understanding of these complexes can assist future rational drug discovery.

* co-corresponding authors

1. Liang, S.*, & Blundell, T. L.* 2023. Human DNA-dependent protein kinase activation mechanism. Nature Structural & Molecular Biology, 30, 140-147.
2. Liang, S.*, Thomas, S.E., Chaplin, A.K., Hardwick, S.W., Chirgadze, D., Blundell, T.L.*, 2022. Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs. Nature, 601, 643–648.
3. Liang, S., Chaplin, A.K., Stavridi, A.K., Appleby, R., Hnizda, A. and Blundell, T.L., 2021. Stages, scaffolds and strings in the spatial organisation of non-homologous end joining: Insights from X-ray diffraction and Cryo-EM. Progress in Biophysics and Molecular Biology, 163, 60-73.
4. Chaplin, A.K., Hardwick, S.W., Liang, S., Stavridi, A.K., Hnizda, A., Cooper, L.R., De Oliveira, T.M., Chirgadze, D.Y. and Blundell, T.L., 2021. Dimers of DNA-PK create a stage for DNA double-strand break repair. Nature Structural & Molecular Biology, 28(1),13-19.
5. Chaplin, A.K., Hardwick, S.W., Stavridi, A.K., Buehl, C.J., Goff, N.J., Ropars, V., Liang, S., De Oliveira, T.M., Chirgadze, D.Y., Meek, K., Charbonnier, J.B. and Blundell, T.L., 2021. Cryo-EM of NHEJ supercomplexes provides insights into DNA repair. Molecular cell, 81(16), 3400-3409.
6. Thapar, R., Wang, J.L., Hammel, M., Ye, R., Liang, K., Sun, C., Hnizda, A., Liang, S., Maw, S.S., Lee, L., Villarreal, H., Forrester, I., Fang, S., Tsai, M.S., Blundell, T.L., Davis, A.J., Lin, C., Lees-Miller, S.P., Strick, T.R., Tainer, J.A., 2020. Mechanism of efficient double-strand break repair by a long non-coding RNA. Nucleic acids research, 48(19),10953-10972.
7. Kefala Stavridi, A., Appleby, R., Liang, S., Blundell, T.L. and Chaplin, A.K., 2020. Druggable binding sites in the multicomponent assemblies that characterise DNA double-strand-break repair through non-homologous end joining. Essays in Biochemistry, 64(5), 791-806.
8. Wu, Q., Liang, S., Ochi, T., Chirgadze, D.Y., Huiskonen, J.T. and Blundell, T.L., 2019. Understanding the structure and role of DNA-PK in NHEJ: How X-ray diffraction and cryo-EM contribute in complementary ways. Progress in biophysics and molecular biology, 147, 26-32.
9. Wang, J.L., Duboc, C., Wu, Q., Ochi, T., Liang, S., Tsutakawa, S.E., Lees-Miller, S.P., Nadal, M., Tainer, J.A., Blundell, T.L. and Strick, T.R., 2018. Dissection of DNA double-strand-break repair using novel single-molecule forceps. Nature structural & molecular biology, 25(6), 482-487.
10. Liang, S., Esswein, S. R., Ochi, T., Wu, Q., Ascher, D. B., Chirgadze, D., Sibanda, B.L. and Blundell, T. L., 2017. Achieving selectivity in space and time with DNA double-strand-break response and repair: molecular stages and scaffolds come with strings attached. Structural Chemistry, 28(1), 161-171.

• https://www.bioc.cam.ac.uk/news/accelerating-cancer-drug-development-targeting-dna-repair-protein

• https://zhuanlan.zhihu.com/p/607947756