The global emergence of epidemic dengue and other Aedes-borne flaviviruses is fuelled in part by an incomplete understanding of the determinants of immunity against these viruses and the molecular underpinnings of disease pathogenesis. My laboratory aims to address these critical gaps in knowledge at the interface between clinical epidemiology, virology and immunology. We combine molecular virology and host response investigations with epidemiological investigations and experimental medicine studies, including clinical trials. Specifically, we are interested in elucidating: (1) the mechanisms that govern the clinical and epidemiological fitness of flaviviruses; (2) the immune responses necessary for flaviviral immunity and infection enhancement; and (3) the molecular correlates of clinical outcome of flaviviral infection. By developing deeper understanding in these areas, we hope to contribute to the development of effective vaccines and treatment against dengue and other Aedes-borne flaviviruses.
Studies on flaviviral infection and vaccines in humans have also enabled us to bring our approach in interfacing bench and bedside research to bear on other viral infections and development of non-flaviviral vaccines. ViREMiCS is thus actively working with both academic and industry partners to develop molecular correlates of safety and efficacy to evaluate novel therapeutics and vaccines, including those for COVID-19.
Manokaran G, Finol E, Wang C, Gunaratne J, Bahl J, Ong EZ, Tan HC, Sessions OM, Ward AM, Gubler DJ, Harris E, Garcia-Blanco M and Ooi EE (2015). Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness. Science, 350:217-21.
Chan KR, Wang X, Saron WA, Gan ES, Tan HC, Mok DL, Zhang SL, Lee YH, Liang C, Wijaya L, Ghosh S, Cheung YB, Tannenbaum SR, Abraham SN, St John AL, Low JG and Ooi EE (2016). Cross-reactive antibodies enhance live attenuated virus infection for increased immunogenicity. Nat Microbiol, 1:16164.
Kwek SS, Watanabe S, Chan KR, Ong EZ, Tan HC, Ng WC, Nguyen MTX, Gan ES, Zhang SL, Chan KWK, Tan JH, Sessions OM, Manuel M, Pompon J, Chua C, Hazirah S, Tryggvason K, Vasudevan SG and Ooi EE (2018). A systematic approach to the development of a safe live attenuated zika vaccine. Nat Commun, 9:1301.
Wilder-Smith A, Ooi EE, Horstick O, Wills B (2019). Dengue. Lancet 393:350-63.
Chan KR, Gan ES, Chan CYY, Liang C, Low JZH, Zhang SL, Ong EZ, Bhatta A, Wijaya L, Lee YH, Low JG, Ooi EE (2019). Metabolic perturbations and cellular stress underpin susceptibility to symptomatic live attenuated yellow fever infection. Nat Med, 25;1218-1224.
Ng KH, Zhang SL, Tan HC, Kwek SS, Sessions OM, Chan CY, Liu ID, Lee CK, Tambyah PA, Ooi EE*, Yap HK* (2019). Persistent dengue virus infection in an immunosuppressed host reveals the roles of humoral and cellular immune responses. Cell Host Microbe, 26:601-605. *Equal contribution.
Ong EZ, Chan YZF, Leong WY, Lee NMY, Kalimuddin S, Haja Mohideen, SM, Chan KS, Tan A, Bertoletti A, Ooi EE*, Low JG* (2020). A dynamic immune response shapes COVID-19 disease progression and resolution. Cell Host Microbe, 27:879-882.e2. *Co-corresponding authors.
Syenina A, Vijaykrishna D, Gan ES, Tan HC, Choy MM, Siriphanitchakorn T, Cheng C, Vasudevan SG, Ooi EE (2020). Positive epistasis between viral polymerase and 3’ untranslated region of its genome reveals epidemiological fitness of dengue virus. Proc Natl Acad Sci USA, 117:11038-11047.
Choy MM, Ng D, Siriphanitchakorn T, Ng WC, Sundstrom KB, Tan HC, Zhang SL, Chan KWK, Manuel M, Kini RM, Chan KR, Vasudevan SG, Ooi EE (2020). A non-structural 1 protein G53D substitution attenuates a clinically-tested live dengue vaccine. Cell Reports, 31:107617.
Gan ES, Tan HC, Thi Le DH, Huynh TT, Wills B, Seidah NG, Ooi EE*, Yacoub S* (2020). Dengue virus induces PCSK9 expression to alter antiviral responses and disease outcomes. J Clin Invest, 130:5223-5234. *Co-corresponding authors.
Yau C, Gan ES, Kwek SS, Tan HC, Ong EZ, Hamis NZ, Rivino L, Chan KR, Watanabe S, Vasudevan SG, Ooi EE (2020). Live vaccine infection burden elicits adaptive humoral and cellular immunity required to prevent Zika virus infection. EBioMedicine, 61:103028.
Low JG, Ng JHJ, Ong EZ, Kalimuddin S, Wijaya L, Chan YFZ, Ng DHL, Tan HC, Baglody A, Chionh YH, Lee DCP, Budigi Y, Sasisekharan R, Ooi EE (2020). Safety and efficacy of a therapeutic anti-yellow fever virus human antibody. N Engl J Med, 383:452-459.