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:
- Subhra BISWAS
- Florent GINHOUX
- Lai Guan NG
- Ee Chee REN
- 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.