Main Appointments
- Group Leader, Singapore Immunology Network (SIgN, A*STAR, Singapore)
- Visiting Scientist, National Cancer Centre Singapore (NCCS, Singapore)
Research Focus
Our research focuses on the systematic discovery and validation of novel therapeutic targets for immunotherapy of solid tumours using focused functional genetic and pharmacological screens, beginning with hepatocellular carcinoma. Hepatocellular carcinoma
(HCC) is the primary form of liver cancer and a highly lethal disease (>900,000 new cases and >800,000 deaths globally every year), with most cases occurring in East and Southeast Asia. HCC is most commonly detected at an advanced stage that
is typically fatal within a year if left untreated. Although recent successes with combination immunotherapies have revolutionised treatment options for HCC, about two-thirds of patients with advanced HCC still do not respond to any kind of therapy.
A critical gap in the rational design of the next generation of effective HCC immunotherapeutics is the paucity of knowledge of dominant immunosuppressive molecular pathways specific to the liver and to the HCC tumour microenvironment.
My group uses two approaches to uncover targets:
- High-throughput functional phenotypic in vitro screening of drugs for their ability to block the immunosuppression of activated CD8 T cells by liver-resident cells. Click here for an example from my previous work where we used a similar approach to discover a novel role for the epigenetic regulator HDAC3 in regulating CD8 T cell cytotoxicity.
- Focused CRISPR-Cas9 genetic screening of potential target molecules on tumour-infiltrating CD8 T cells in mouse models of HCC. Click here for an example from my previous
work where we used a similar approach to identify the epigenetic regulator CARM1 as a potential target for immunotherapy in a mouse model of melanoma that is highly resistant to immunotherapy.
By combining these two approaches, we aim to discover immunosuppressive molecular drivers and pathways intrinsic to the liver and specific to the HCC tumour microenvironment, respectively.
More recently, we have developed a high-throughput platform for magnetic particle imaging (MPI) of adoptively transferred immune cells labelled with magnetic nanoparticles. This platform uses a custom-built MPI device developed by our partner, Dr Tay Zhi Wei (formerly from IBB, currently moved to National Institute of Advanced Industrial Science and Technology, Japan) and is capable of imaging 5 mice in one sitting for at least two weeks following cell transfer,
enabling the longitudinal monitoring of their dynamics in real-time and accelerating research in cell therapies for solid tumours.
Overall, our research aims to generate validated, high-confidence targets for the downstream development of rationally engineered therapeutics and cell therapy products in partnership with clinicians driving clinical trials and with industry partners.