Infectious Diseases

Overview

The SIgN Infectious Diseases program uses deep immunophenotyping to identify the underlying pathological mechanisms of immune cells, pathogens and molecules in various vector-borne, bacterial and viral diseases. Using the SIgN Human Monoclonal Antibody Platform, our researchers are developing new biologics for testing in pre-clinical models of infection (including humanized and normal mice and non-human primates) with the aim of translating these findings to the clinic. Using the SIgN Immunomonitoring Platform, our researchers are discovering predictive biomarkers and developing new therapeutic strategies and point-of-care diagnostic technologies for translation at the clinical level.

The Infectious Diseases program covers four main themes:

Vector-borne diseases: including Dengue virus, Chikungunya virus, Zika virus and Malaria

Bacterial and viral diseases: including Tuberculosis and Hepatitis B virus

Anti-microbial resistance: including Candida infection, Carbapenme-resistant Enterobacteriaceae, and microbiome research

Immunomonitoring: by deep immune-phenotyping, immunogenomics and studies of the immune repertoire

Principal Investigators involved include:

Pablo BIFANI
Subhra BISWAS
Katja FINK
Florent GINHOUX
Benoit MALLERET
Evan NEWELL
Lai Guan NG
Lisa NG
Norman PAVELKA
Ee Chee REN
Laurent RENIA
Amit SINGHAL
Cheng-I WANG

Click here to visit the Principal Investigators page. 

Research Highlights

The data produced by the researchers of this program has been recognized for its high scientific excellence, as indicated by numerous successful publications in high impact journals, including Science, Translational Medicine, Blood and Nature Medicine (see below). Furthermore, the studies conducted by our researchers have health, economic and industrial impact. Examples of the translational research conducted, and novel discoveries and innovative technologies contributed by the program include:

• Preclinical development of a potent therapeutic antibody against dengue
• Novel dengue vaccine for low endemic countries
• Effective therapeutic for Chikungunya arthralgia
• Unique assay for anti-malarial drug discovery
• A biochip to detect tropical diseases (VereChip™)

Based on such developments, external partnerships with numerous industry partners have been established, including Chugai, Merck, Janssen and Novartis.

Finally, the Infectious Diseases program has established various cohorts for Dengue, Chikungunya and Zika virus (at the Communicable Disease Centre at Tan Tock Seng Hospital) as well as various Thai, Brazilian, Indian and South African vector-borne diseases cohorts. In addition, the program has established the A*STAR Zika Alliance that we are currently leading (other parties involved include: Bioprocessing Technology Institute, the Bioinformatics Institute, Nanyang Technological University and Communicable Disease Centre at Tan Tock Seng Hospital).

The Infectious Disease program has international collaborations with researchers including at: The Chancellor, Masters and Scholars of The University of Oxford, UK; the University of Campinas, Brazil;  the Cinvestav, Mexico; the Translational Health Science and Technology Institute, India; The New York College of Technology, USA. 

Key Publications

Rivino L et al. Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation. J Clin Invest. 2018.

Gruszczyk J et al. Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax. Science. 2018.

Ko HL et al. Identification of Slug and Sox7 as transcriptional repressors binding to the Hepatitis B Virus Core Promoter. J Hepatol. 2017.

Kam YW et al. Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections. JCI Insight. 2017.

Kosaisavee V et al. Strict Tropism for CD71+/ CD234+ Human Reticulocytes Limits Plasmodium cynomolgi's Zoonotic Potential. Blood. 2017.

Teo TH et al. Fingolimod treatment abrogates chikungunya virus-induced arthralgia. Sci Transl Med. 2017.

Her Z et al. Severity of Plasma Leakage Is Associated With High Levels of Interferon γ-Inducible Protein 10, Hepatocyte Growth Factor, Matrix Metalloproteinase 2 (MMP-2), and MMP-9 During Dengue Virus Infection. J Infect Dis. 2017.

Howland SW et al. Activated Brain Endothelial Cells Cross-Present Malaria Antigen. PLoS Pathog. 2015.

Zhang R et al. A basis for rapid clearance of circulating ring-stage malaria parasites by the spiroindolone KAE609. J Infect Dis. 2016.

Teng TS et al. A Systematic Meta-analysis of Immune Signatures in Acute Chikungunya Virus-infected Patients. J Infect Dis. 2015.

Lee WW et al. Expanding regulatory T cells alleviates chikungunya virus-induced pathology in mice. J Virol. 2015.

Teo TH et al. Chikungunya virus isolates differ in their capacity to induce pro-inflammatory Th1 and NK cell responses and acute joint pathology. J Virol. 2015.

Singhal A et al. Metformin as adjunct anti-tuberculosis therapy. Science Translational Medicine. 2014. 

Lepore M et al. A novel self-lipid antigen targets human T cells against CD1c+ leukemias. J Exp Med. 2014.

Lepore M et al. Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire. Nat Commun. 2014.

Click here to visit the full SIgN Publications page.