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Temporospatial Immunomic Genomic Experimentable Research (TIGER)

Our Mission

Our mission is to participate in world-leading & game-changing research that addresses the most pressing problems in GI cancers. We seek to identify specific situations where advances in science & technology intersect with current challenges in the clinical management of these cancers. Through multi-disciplinary collaborations, we aim to generate meaningful knowledge that lead to solutions that can effect dramatic improvements in patient outcomes.

Our approach is to sustain a comprehensive cohort of patients with serial tumor and blood samples collected across the patient’s journey with cancer to understand how the patient’s cancer changes spatiotemporally with treatment and time. We process patient samples in a manner compatible with the establishment of patient derived tumor models and isolate various components, e.g. immune cells, prospectively.

Detailed study description

Prospective observational cohort with prospectively processed samples optimal for biological interrogation

Prospective observational study:

  • > 1,200 patients with serial clinical samples, for -omic analysis of patient samples across clinically relevant events
  • > 8,000 serial plasma and buffy coat or PBMC samples
  • 500 serial time point frozen tumor tissues from ~ 200 patients
  • 50 patient-derived tumor models (PDXs, 2D/3D Patient derived lines including spheroids/ organoids) (together with Dr. Dasgupta Ramanaj from NCCS/GIS)
  • “Living Processed Biobank”: > 50 additional tumors processed & slow frozen viable either for future establishment of tumor models or for molecular omic analyses
  • 80 tumors with freshly isolated tumor infiltrating lymphocytes kept frozen viable (together with Dr. Evan Newell from SIgN, A*STAR)

Translational Research Priority Areas:

  • Real-time diagnostics / biology /intervention, led by Dr. Iain Tan (MBBS, PhD): Perform -omic analysis of serial patient samples to characterize molecular evolution over time using leading edge technologies (ctDNA, CTCs, scRNASeq, metabolomics, proteomics) for diagnostics/ therapeutics Development of -omic informed therapeutic strategies e.g. neoantigen vaccines and ctDNA informed anti-metastatic therapy
  • Tumor models, led by Dr Clarinda Chua (MBBS, MCI): Patient derived tumor models to functionally characterize and perturb processes in drug resistance and metastasis
  • Immunology, led by Dr. Koo Si-Lin (MBBS, MMed): Comprehensive immunophenotyping to characterize the immune landscape and immunological vulnerabilities of colorectal cancer (Cytoff / TCR repertoire studies)

Research Benchmarks

  • Multiple productive local/international collaborations
  • Multiple international & local research awards
  • More than $5 million in national competitive research funding (last 3 years)
  • > 50 publications including Nature Medicine, Nature Genetics, Immunity, Science Translational Medicine, JCO, Lancet Oncology, Cancer Research (last 3 years)

Selected publications:

  1. Li H #, Courtois ET #, Sengupta D, Tan Y, Chen KH, Kong SL, Chua C, Hu Y, Wee L, Hon LK, Tan WS, Wong M, Choi PJ, Wee L, Hillmer AM, Tan IB *, Robson P*, Prabhakar S* (co-corresponding author) Reference Component Analysis of Single Cell Transcriptomes Reveals Cellular Heterogeneity in Human Colorectal Tumors. Nature Genetics 2017 (in press)
  2. Suzuki Y, Ng SB, Chua C, Leow WQ, Chng J, Liu SY, Ramnarayanan K, Gan A, Ho DL, Ten R, Su Y, Lezhava A, Lai JH, Koh D, Lim KH, Tan P, Rozen SG, Tan IB. Multiregion ultra-deep sequencing reveals early intermixing and variable levels of intratumoral heterogeneity in colorectal cancer. Mol Oncol. 2017 Feb;11(2):124-139.
  3. Ng SB, Chua C, Ng M, Gan A, Poon PS, Teo M, Fu C, Leow WQ, Lim KH, Chung A, Koo SL, Choo SP, Ho D, Rozen S, Tan P, Wong M, Burkholder WF, Tan IB. Individualised multiplexed circulating tumour DNA assays for monitoring of tumour presence in patients after colorectal cancer surgery. Sci Rep. 2017 Jan 19;7:40737.
  4. Simoni Y, Fehlings M, Kløverpris HN, McGovern N, Koo SL, Loh CY, Lim S, Kurioka A, Fergusson JR, Tang CL, Kam MH, Dennis K, Lim TK, Fui AC, Hoong CW, Chan JK, Curotto de Lafaille M, Narayanan S, Baig S, Shabeer M, Toh SE, Tan HK, Anicete R, Tan EH, Takano A, Klenerman P, Leslie A, Tan DS, Tan IB, Ginhoux F, Newell EW. Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency. Immunity. 2017 Jan 17;46(1):148-161.
  5. Fukawa T, Chua BY, Chua JM, Tan EJ, Huang D, Qian C, Ong P, Li ZM, Chen SW, Mak SY, Elsa Mohan S, Wang RR, Lim WJ, Kanayama H, Lai JH, Chua C, Ong HS, Tan KK, Ho YS, Tan IB*, Teh BT*, Ng SC* Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia. Nature Medicine 2016 online 2 May 2016 2016 Jun;22(6):666-71. (IF 2730.3) *Co-corresponding author
  6. Tan IB, Malik S, Ramnarayanan K, McPherson JR , Ho DL, Suzuki Y, Ng SB, Su Y, Lim KH, Koh K, Chew MH, Chan CY, Ten R, Goh BKP, Chung AYF, Tan J, Chan CX, Tay ST, Lezhava A, Nagarajan N, Hillmer AM, Tang CL, Chua C, Teh BT, Rozen S, Tan P. 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 Biology 2015 Feb 12;16:32
  7. Lei Z, Tan IB, Das K, Deng N, Zouridis H, Pattison S, Chua C, Feng Z, Guan YK, Ooi CH, Ivanova T, Zhang S, Lee M, Wu J, Ngo A, Manesh S, Tan E, Teh BT, So JB, Goh LK, Boussioutas A, Lim TK, Flotow H, Tan P, Rozen SG. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil. Gastroenterology. 2013 Sep;145(3):554-65.
  8. Ku G*, Tan IB*, Yau T, Boku N, Laohavinij S, Cheng AL, Kang YK, de Lima Lopes G Jr (2012) Management of colon cancer: resource-stratified guidelines. 2012 Lancet Oncol 13(11):e470-81 (co-first)
  9. Tan IB, Ivanova T, Lim KH, Ong CW, Deng N, Lee J, Tan SH, Wu J, Lee MH, Ooi CH, Rha SY, Wong WK, Boussioutas A, Yeoh KG, So J, Yong WP, Tsuburaya A, Grabsch H, Toh HC, Rozen S, Cheong JH, Noh SH, Wan WK, Ajani JA, Lee JS, Tellez MS, Tan P. Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy. Gastroenterology. 2011 Aug;141(2):476-85, 485.e1-11.
  10. Tan IB, Cutcutach I, Zhi Jiang Zang, Iqbal J, Yap SF, Hwang W, Lim WT, Rozen S, Tan EH, Tan P. Fanconi's Anemia in Adulthood: Chemoradiation-Induced Bone Marrow Failure and a Novel FANCA Mutation Identified by Targeted Deep Sequencing. J Clin Oncol April 2011