Professor Lok is a recipient for the prestigious National Research Foundation (NRF) fellowship (2009) and NRF Investigatorship (2016). The research in her laboratory focuses on understanding the pathology of flavivirus and alphavirus infections and the mechanism of neutralization by antibodies and other molecules so as to facilitate the development of suitable vaccines and therapeutics. A combination of molecular, immunological, biochemical and structural techniques (x ray crystallography and cryoEM image reconstruction techniques) are used to achieve these aims.
Lok lab uses structural methods such as x-ray crystallography and cryo-electron microscope to study viruses in particular, flaviviruses (dengue and Zika viruses) and alphavirus (Sindbis and Chikungunya viruses). We study the
- Interactions and structural changes of viruses during their infection process, for example:
- How virus binds to its host cell receptor(s)
- How virus fused with its endosomal membrane
- How newly synthesized virus in the cell is assembled
- How virus undergo maturation in the cell.
- Understand how therapeutics such as antibodies could inhibit various stages of the infection process.
- Look at the different possible morphologies of flaviviruses and alphaviruses. This has important implications in the development of vaccine.
All these knowledge will contribute to therapeutics and vaccine development.
Visit Shee-Mei Lok lab here.
https://pubmed.ncbi.nlm.nih.gov/?cmd=search&term=Lok SM[au] and Singapore
Selected publications:
Qun Fei Zhou, Julie M. Fox, James T. Earnest, Thiam-Seng Ng, Arthur S. Kim, Guntur Fibriansah, Victor A. Kostyuchenko, Jian Shi, Bo Shu, Michael S. Diamond, Shee-Mei Lok (2020) Structural basis of Chikungunya virus inhibition by monoclonal antibodies. Proc Natl Acad Sci U S A. 117:27637.
Seamus R. Morrone, Valerie S. Y. Chew, Xin-Ni Lim, Thiam-Seng Ng, Victor A. Kostyuchenko, Shuijun Zhang, Melissa Wirawan, Pau-Ling Chew, Jaime Lee, Joanne L. Tan, Jiaqi Wang, Ter Yong Tan, Jian Shi, Gavin Screaton, Marc C. Morais, Shee-Mei Lok (2020) Tremendous flavivirus structural plasticity demonstrated by a new morphological variant. Nature Communications. Vol 11:3112.(IF:12)
Ter Yong Tan, Guntur Fibriansah, Victor A. Kostyuchenko, Thiam-Seng Ng, Xin-Xiang Lim, Shuijun Zhang, Xin-Ni Lim, Jiaqi Wang, Jian Shi, Marc C. Morais, Davide Corti, Shee-Mei Lok (2020) Capsid protein structure in Zika virus reveals the flavivirus assembly process. Nature Communications Vol 11(1):895.
Jiaqi Wang, Marco Bardelli, Diego A. Espinosa, Mattia Pedotti, Thiam-Seng Ng, Siro Bianchi, Luca Simonelli, Elisa X.Y. Lim, Mathilde Foglierini, Fabrizia Zatta, Stefano Jaconi, Martina Beltramello, Elisabetta Cameroni, Guntur Fibriansah, Jian Shi, Taylor Barca, Isabel Pagani, Alicia Rubio, Vania Broccoli, Elisa Vicenzi, Victoria Graham, Steven Pullan, Stuart Dowall, Roger Hewson, Simon Jurt, Oliver Zerbe, Karin Stettler, Antonio Lanzavecchia, Federica Sallusto, Andrea Cavalli, Eva Harris, Shee-Mei Lok*, Luca Varani*, Davide Corti* (2017) A human bi-specific antibody against Zika virus with high therapeutic potential. Cell. Vol 171:229-241. *co-corresponding authors.
Kostyuchenko VA, Lim EX, Zhang S, Fibriansah G, Ng TS, Ooi JS, Shi J, Lok SM. (2016).Structure of the thermally stable Zika virus. Nature. 533:425-428.
Guntur Fibriansah, Kristie D. Ibarra, Thiam-Seng Ng, Scott A. Smith, Joanne L. Tan, Xin-Ni Lim, Justin S. G. Ooi, Victor A. Kostyuchenko, Jiaqi Wang, Aravinda M. de Silva, Eva Harris, James E. Crowe, Jr. and Shee-Mei Lok. (2015). A human antibody locks dengue virus E protein dimers and prevents antibody-enhanced severe disease. Science. Vol 349:88-91.
Guntur Fibriansah, Joanne L. Tan, Scott A. Smith, Ruklanthi de Alwis, Thiam-Seng Ng, Victor A. Kostyuchenko, Ramesh S. Jadi, Petra Kukkaro, Aravinda M. de Silva, James E. Crowe, Jr. and Shee-Mei Lok. (2015). A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins. Nature Communications. Vol 6:6341.