Associate 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.
Shee-Mei Lok. (2018). Flat-lying antibody prevents disease enhancement. Nature Immunology, In press.
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. (2018). Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody. Structure, In press.
Shee-Mei Lok. (2018). Inhibiting EBV: The Key to Carefree Smooching. Immunity., 48(4):623-625. Pubmed ID: 29669245
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. Pubmed ID: 29522750
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. Pubmed ID: 28968838