Lok, Shee Mei

Research Interests:

Assistant Professor Lok is one of the recipients for the prestigious National Research Foundation fellowship. Dengue Virus (DENV) infects approximately 100 million people each year. Increased travel, together with global climate change will result in further geographical expansion of the territory of the dengue mosquito vector, Aedes aegypti. There is an urgent need to develop safe and effective dengue therapeutics and vaccine.

In vitro experiments have shown that non-neutralizing antibodies can enhance DENV infection of Fc receptor bearing macrophages, one of the natural host cells for the virus. This suggested that the presence of non-neutralizing epitopes in a vaccine could potentially increase the chances that a person who had received the vaccine would develop the severe form of the disease, dengue hemorrhagic fever. For this reason, a more promising approach for engineering an effective DENV vaccine is to focus on including neutralizing epitopes. Thus, mapping of neutralizing epitopes is a necessary component of DENV vaccine research. Furthermore, understanding the neutralization mechanism of antibodies and the entry of DENV into the host cells also could aid in the design of targeted therapeutics.

The research in her laboratory therefore, focuses on the understanding of the pathology of dengue virus infection 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) will be used to achieve these aims.

Selected Publications:

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.

Chang WS, Shang H, Perera R, Lok SM, Sedlak D, Kuhn RJ, Lee GU. (2008). Rapid detection of dengue virus in serum using Magnetic separation and fluorescence detection. The Analyst.132(2): 233-240.

Lok SM, Gao R, Rouault M, Lambeau G, Gopalakrishnakone P, Swaminathan K. (2005). Structure and function comparison of Micropechis ikaheka snake venom phospholipase A2 isoenzymes. FEBS J. 272(5):1211-20.

Zhang DH, Li N, Lok SM, Zhang LH, Swaminathan K. (2003). Isomaltulose Synthase (PalI) of Klebsiella sp. LX3: Crystal Structure and implication of mechanism. J Biol Chem. 278 (37): 35428-35434.

Lok SM, Ng ML, Aaskov J. (2001). Amino acid and phenotypic changes in dengue 2 virus associated with escape from neutralization by IgM antibody. J Med Virol. 65(2): 315-323.