Lisa graduated in Biochemistry from the University of Manchester Institute of Science and Technology (UMIST) in the United Kingdom in 1995. She then obtained her PhD in Molecular Virology in coronaviruses from the National University of Singapore (NUS) in 2002. After joining the Genome Institute of Singapore (GIS) in 2002 as a post-doctoral fellow, Lisa has made significant scientific contributions to the field where she worked on viral diseases such as hepatitis, SARS and influenza. Her contributions involved academia to public health in developing a framework to deliver broad-range capability for disease preparedness.
She is currently the Executive Director and Senior Principal Investigator at A*STAR Infectious Diseases Labs (ID Lab), and the research interest of her group (Microbial Immunity Lab) focuses on the immune responses of arthritic arboviruses that are epidemic or highly endemic in the tropical region. Her research group became a member of ICRES (Integrated Chikungunya RESearch), a European Union Frame-work Program 7 funded project in 2009 and has since published several studies in top tier scientific journals. These studies provided key findings to move the human immunology field forward in controlling the rising number of CHIKV infections.
For her previous work and contributions to SARS, she was voted “Most Inspiring Woman” at the Great Women of Our Time Awards for Science and Technology in 2005, and was confered the Junior Chamber International (JCI) “Ten Outstanding Young Persons of the World” Singapore 2013 Scientific and/or Technological Development Award. In recognition of her meritorious research and development efforts on Asia’s infectious diseases, she was conferred the highly prestigious ASEAN (Association of South-East Asian Nations) “International Young Scientist and Technologist Award” in 2008.
Lisa also hold adjunct Professorships with the Department of Biochemistry, Yong Loo Lin School of Medicine at the ‘National University of Singapore’ (NUS), and at the ‘Duke-NUS’ Graduate Medical School. In recognition of her mentoring work for graduate students and scientists, she received the A*STAR “Most Inspiring Mentor Award” in March 2013.
- Adjunct Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS, Singapore
- Adjunct Professor, Emerging Infectious Diseases Program, Duke-NUS, Singapore
- Adjunct Professor, Lee Kong Chien School of Medicine, NTU, Singapore
Infectious diseases are responsible for 26% of the annual deaths worldwide. A substantial fraction is caused by viral pathogens. Globalisation, increased mobility and environmental change, results in a highly increased chance of pandemics of new and re-emerging viral diseases that impose a tremendous threat for public health. Among them, vector-borne infectious diseases have been resurging due to climate change, socio-demographic changes, and genetic mutations in the pathogens. One such disease is Chikungunya Fever (CHIKF), which has emerged as the next important infection in South-East (SE) Asia, the Pacific region and Europe, making it a major threat. It is caused by an alphavirus, Chikungunya virus (CHIKV) and is transmitted by Aedes mosquitoes, CHIKV was first isolated in 1953 in East Africa and has since been associated with periodic outbreaks of human disease.
It is a debilitating disease with abrupt fever onset, rash or haemorrhages, arthralgia and occasional involvement of the nervous system, heart and liver. Persistent incapacitating arthralgia has been recorded to persist for years. The clinical features of recent acute CHIKV infections have been described, however, the long-term sequelae or the pathogenesis of arthropathy, and the acquisition of protective immunity remains unexplored. There is no specific or effective treatment for CHIKF, and patient management is largely palliative and principally based on anti-inflammatory drugs. Given the expanding geographic range of CHIKV and its potential to rapidly cause large scale epidemics, it has become important to understand the immune and pathogenic mechanisms active during CHIKV infections in order to guide the development of targeted and effective control and treatment strategies. Efforts are aimed at gathering fundamental knowledge on the immune responses mounted against CHIKV to exploit this to develop new immune-based preventive and treatment strategies.
Integrated approaches will be applied and will include identification of prognostic markers for improved clinical management of disease, further understanding of disease immune-pathology, generation of tools required for murine models, and tools for immune-monitoring and vaccine development.
Schematic representation of CHIKV dissemination after mosquito bite
Aedes mosquito inoculates CHIKV into intradermal compartments. Resident immune cells in the intradermal layer include dendritic cells (DCs), Langerhans cells (LC), macrophage (MØ) and neutrophils that can interact and contain CHIKV from further virus dissemination. CHIKV-infected cells may migrate to the draining lymph nodes and trigger innate immune response for virus elimination. However, virus escaped from lymph nodes may release into blood circulation and disseminate to various parts of the body. Picture taken from Kam et al., 2009 Microbes and Infection.
A. Electron microscopy of CHIKV. B. Atomic force microscopy of CHIKV
Pictures taken by Jason Kam, Senior Research Fellow and can be found in Her et al., 2009 Microbes and Infection.
Genome organization of CHIKV. The RNA genome contains a 5’ methylated cap and a 3’ polyadenylated structure. It also functions as a RNA template for genome replication within the infected cells. Four non-structural genes encoding the replicase (nsP1 and nsP3), helicase (nsP2), and polymerase (nsP4), and the 5 structural proteins (Capsid-E3-E2-6K-E1). Picture can be found in Teng et al., 2011 Future Virology.
Schematic representation of immune response against CHIKV infection
CHIKV viremia in blood lasts between 2 and 10 days (viral load in red filled area). Specific CD4þ (blue line) and CD8þ T cells (purple line) are expanded corresponding to CHIKV infection. Rapid virus elimination occurs before the expansion of neutralising antibodies (IgG, green line), Clinical symptoms (fever) disappear when CHIKV viremia drops below the level of detection.
Picture can be found in Kam et al., 2009 Microbes and Infection.
Postulated anti-CHIKV signalling cascades by TLR-dependent, RIG-I-dependent, IFN-α/β induction, and IFN-α/β mediated JAK/STAT signalling pathways.
Upon infection of target fibroblasts, the presence of CHIKV RNA in the cytosol triggers innate host response. MDA-5 and RIG-I may act as the potential PRRs to signal to IRFs in a IPS-1 dependent pathway to induce expression of the expression IFN-α/β via activation of IRFs. Alternatively, recognition of CHIKV RNA in the endosomes by TLR 3, 7, 8 and that of viral glycoproteins by TLR 4 can act as possible sensors that signal through various adaptor proteins such as TRIF, TRAM and MyD88 to mediate IFN-α/β induction. Consequentially, the secretion and binding IFN-α/β to its receptors will trigger the activation of the JAK/STAT pathway to amplify the production of IFN-α/β in a positive feedback loop, together with the induction of a variety of cytokines, chemokines and ISGs. In order to evade the innate host response, CHIKV has been shown to induce the shutdown of host transcriptional and translation machinery as well as inhibiting the activation of the IFN-α/β mediated signalling. Picture can be found in Teng et al., 2011 Future Virology.
Co-staining of CHIKV antigens (green) with membrane markers (red)
Pictures taken by Preston Teng, Senior Research Fellow
Importance of animal models in the study of CHIKV disease pathogenesis and treatments
Picture can be found in Teo et al., 2012 Immunological Research.
The use of animal models in CHIKV research remains vital as it not only provides the opportunity to understand the immune-pathogenesis of CHIKV, but will serve as a platform for the development of CHIKV vaccines and therapeutics against CHIKV
Picture can be found in Kam et al., 2012 EMBO Molecular Medicine
|Siew Wai FONG
|Anthony TORRES RUESTA
|Liang Hui LOO
Lisa Ng's ID Labs affiliated publications (last updated Jul 2021)