Translational Research in Gastrointestinal Cancer

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We’re a translational research team. Our approach is to identify specific situations where advances in science and technology can be exploited to overcome the current challenges in the clinical management of gastrointestinal (GI) cancer. We focus on three areas:

1. Realtime diagnostics (Lead: Iain Tan), non-invasive testing with circulating cell-free DNA;
2. Metastasis (Lead: Clarinda Chua); and
3. Immuno-oncology (Co-Lead: Iain Tan, Koo Si-Lin).

Our approach uses multi-omics analyses of colorectal cancer sets (WGS / WTS / whole proteome / metabolomic / microbiome) with one of the largest pan-omic sets of GI cancers globally. We use patient-derived tumour models for studies in metastases and immune cells (tumour-infiltrating and peripheral immune cells) with corresponding patientderived tumour models for studies in immunotherapy. We are performing window-of-opportunity clinical studies with pre-op immunotherapy and studies towards neoantigen vaccine therapy. Our laboratory has published widely, with publications in Nature, Nature Genetics, Nature Medicine, Science Translational Medicine, Immunity, Annals of Medical Oncology, among others. We have multiple national research grants and are involved with several national research programmes. We lead several investigator-initiated trials and also participate in global Phase 2/3 trials.

Selected publications:

1. Li H, Courtois ET, Sengupta D, et al. Reference component analysis of singlecell transcriptomes elucidates cellular heterogeneity in human colorectal tumors. Nat Genet. 2017;49:708–718.
2. Fukawa T, Chua BY, Chua JM, et al. Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia. Nat Med. 2016;22:666–671.
3. Simoni Y, Fehlings M, Becht E, et al. Expression of CD39 distinguishes neo-antigen specific from bystander CD8+ human tumor infiltrating T cells. Nature. 2018, in press.
4. Tan IB, Malik S, Ramnarayanan K, et al. High-depth sequencing of over 750 genes supports linear progression of primary tumors and metastases in most patients with liver-limited metastatic colorectal cancer. Genome Biol. 2015;16:32.
5. Ng SB, Chua C, Ng M, et al. Individualised multiplexed circulating tumour DNA assays for monitoring of tumour presence in patients after colorectal cancer surgery. Sci Rep. 2017;7:40737.