Sheemei Lok

Professor

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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:
  1. How virus binds to its host cell receptor(s)
  2. How virus fused with its endosomal membrane
  3. How newly synthesized virus in the cell is assembled
  4. 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.

Xin-Ni Lim, Chao Shan, Jan K. Marzinek, Hongping Dong, Thiam Seng Ng, Justin S. G. Ooi, Guntur Fibriansah, Jiaqi Wang, Chandra S. Verma, Peter J. Bond, Pei-Yong Shi, Shee-mei Lok (2019) Molecular basis of dengue virus serotype 2 morphological switch from 29oC to 37oC. PLOS Pathogen. Accepted.

Seamus R. Morrone & Shee-Mei Lok. (2019). Structural perspectives of antibody-dependent enhancement of infection of dengue virus. Curr. Opin. Virol., 36:1-8.

Melissa Wirawan, Guntur Fibriansah, Jan K. Marzinek, Xin Xiang Lim, Thiam-Seng Ng, Adelene Y. L. Sim, Qian Zhang, Victor A. Kostyuchenko, Jian Shi, Scott A. Smith, Chandra S Verma, Ganesh Anand, James E. Crowe Jr., Peter J. Bond & Shee-Mei Lok. (2019). Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody. Structure, 27(2):253-267.e8.

Shee-Mei Lok. (2018). Flat-lying antibody prevents disease enhancement. Nature Immunology, 19(11):1150-1152.

Shee-Mei Lok. (2018). Inhibiting EBV: The Key to Carefree Smooching. Immunity., 48(4):623-625.

Felix A. Rey, Shee-Mei Lok. (2018). Common Features of Enveloped Viruses and Implications for Immunogen Design for Next-Generation Vaccines. Cell, 172(6):1319-1334.

Emily N Gallichotte, Kenneth H Dinnon III, Xin-Ni Lim, Thiam-Seng Ng, Elisa X.Y. Lim, Vineet D Menachery, Shee-Mei Lok*, Ralph S Baric* (2017) CD-loop extension in Zika virus envelope protein key for stability and pathogenesis. The Journal of Infectious Diseases. J. Infect. Dis., jix473. *co-corresponding authors.

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, 171(1):229-241.*co-corresponding authors. 

Xin-Xiang Lim, Arun Chandramohan, Xin Ying Elisa Lim, James E. Crowe, Jr., Shee-Mei Lok, Ganesh S. Anand. (2017). Epitope and Paratope Mapping Reveals Temperature-Dependent Alterations in the Dengue-Antibody Interface. Structure, 25(9):1391-1402. 

Shee-Mei Lok. (2017). Unsweetened IgG is bad for dengue patients. Cell Host and Microbes, 21(3):312-314. 

Xin-Xiang Lim, Arun Chandramohan, Xin Ying Elisa Lim, Nirmalya Bag, Kamal Kant Sharma, Melissa Wirawan, Thorsten Wohland, Shee-Mei Lok, Ganesh S. Anand. (2017). Conformational changes in intact dengue virus reveal serotype-specific expansion. Nature Communications, 8:14339.

Shuijun Zhang, Victor A. Kostyuchenko, Thiam-Seng Ng, Xin-Ni Lim, Justin S.G. Ooi, Sebastian Lambert, Ter Yong Tan, Douglas G. Widman, Jian Shi, Ralph S. Baric and Shee-Mei Lok. (2016). Neutralization mechanism of a highly potent antibody against Zika virus. Nature Communications. Vol 7: 13679.

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.

Shee-Mei Lok. (2015). The interplay of dengue virus morphological diversity and human antibodies. Trends in Microbiology. Vol 24(4):284-93.

Shee-Mei Lok. (2014). Human antibodies stop dengue virus by jamming its mechanics. Proceedings of National Academy of Sciences USA. Vol 111:1670-1671.

Victor A. Kostyuchenko, Pau Ling Chew, Thiam-Seng Ng, Shee-Mei Lok (2014). Near-atomic resolution cryo-EM structure of Dengue serotype 4 virus. Journal of Virology. Vol 88: 477-482.

Guntur Fibriansah, Joanne L. Tan, Ruklanthi de Alwis, Scott A. Smith, Thiam-Seng Ng, Victor A. Kostyuchenko, Kristie D. Ibarra, Eva Harris, Aravinda de Silva, James E. Crowe, Jr. and Shee-Mei Lok (2014). A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface. EMBO Molecular Medicine. Vol 6: 358-371.

Guntur Fibriansah, Thiam-Seng Ng, Victor A. Kostyuchenko, Jaime Lee, Sumarlin Lee, Jiaqi Wang, Shee-Mei Lok (2013). Structural Changes in Dengue Virus When Exposed to a Temperature of 37oC. Journal of Virology, Vol 87:7585-92.

Victor A Kostyuchenko, Qian Zhang, Joanne L Tan, Thiam-Seng Ng, Shee-Mei Lok (2013). Immature and mature Dengue serotype 1 virus structures provide insight into the maturation process. Journal of Virology. Vol 87:7700-7.

Ee Ping Teoh, Petra Kukkaro, En Wei Teo, Angeline Lim, Tze Tong Tan, Andy Yip, Wouter Schul, Myint Aung, Victor A. Kostyuchenko, Yee Sin Leo, Soh Ha Chan, Kenneth G.C. Smith, Eng Eong Ooi, D. Michael Kemeny, Grace K. Tan, Jowin K. W. Ng, Mah Lee Ng, Sylvie Alonso, Pei Yong Shi, Dale Fisher, Brendon Hanson, Shee-Mei Lok* and Paul A. MacAry*. (2012). The Structural Basis for Serotype-Specific Neutralization of Dengue Virus by a Natural Human Antibody. Science Translational Medicine. Vol 4:139 * co-corresponding authors

Li L, Lok SM, Yu IM, Zhang Y, Kuhn RJ, Chen J, Rossmann MG. (2008). Structure of the flavivirus precursor membrane-envelope protein complex and its implication for maturation. Science. 319: 1830-1834.

Lok SM, Kostyuchenko V, Nybakken GE, Holdaway HA, Battisti AJ, Sukupolvi-Petty S, Sedlak D, Fremont DH, Chipman PR, Roehrig JT, Diamond MS, Kuhn RJ, Rossmann MG. (2008). Binding of a neutralizing antibody to dengue virus resulted in an altered arrangement of the surface glycoproteins. Nature Structural and Molecular Biology. 15 (3): 312-317.