Group Leader: Dr Chris Tape, Cancer Research UK Career Development Fellow
The human body contains around 40 trillion cells made up from over 200 different cell types. This combination of different cells enables metazoan tissues to achieve complex phenotypes that no one cell type can achieve alone. For example, in the intestine, epithelial cells control nutrient uptake, whereas stromal fibroblasts support epithelial renewal, and tissue-resident leukocytes patrol against infection. No one cell type can perform all these jobs, but together they can collaborate to form a complex tissue epithelium with adaptive immunosurveillance. Such multicellular collaboration requires different cell types to communicate with one another.
Just like healthy intestinal tissue, colorectal cancer (CRC) tumours also contain epithelial, stromal, lymphoid, and myeloid cells. And like healthy tissues, CRC tumours use these different cells to achieve complex phenotypes. The difference with cancer is that these phenotypes (such as immune evasion and metastasis) can kill, rather than aid, the host organism. Unfortunately, we know very little about how the different cell types in cancer communicate with one another to drive tumours.
The Cell Communication Lab studies how oncogenic mutations (e.g. loss of APC, oncogenic KRAS) communicate with stromal and immune cells to drive CRC. By understanding how mutations regulate all cell types within a tumour, we aim to uncover novel approaches to treat cancer.
The lab uses custom cell-specific signalling technologies (such as heterocellular proteomics and single-cell mass-cytometry) to measure how oncogenic signals flow through CRC tumours. We measure heterocellular oncogene signalling in biomimetic organoids in vitro, and clinical samples and genetically engineered mouse models (GEMMs) in vivo.
- C. J. Tape & C. Jørgensen, 'Cell-Specific Labelling For Analysing Bidirectional Signalling by Mass Spectrometry', Kinase Signaling Networks, Methods in Mol. Bio. (2017) 1636: 219-234. PMID: 28730482
- C. J. Tape, 'The Heterocellular Emergence of Colorectal Cancer', Trends in Cancer (2017) 3(2): 79-88. PMID: 28239669
- C. J. Tape, S. Ling, M. Dimitriadi, K.M. McMahon, J.D. Worboys, H.S. Leong, I.C. Norrie, C.J. Miller, G. Poulogiannis, D.A. Lauffenburger, C. Jørgensen, 'Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation', Cell (2016) 165(4): 910–920 PMID: 27087446
- C. J. Tape, 'Systems Biology Analysis of Heterocellular Signaling', Trends in Biotechnology (2016) 34(8). PMID: 27087613
- C. J. Tape, J.D. Worboys, J. Sinclair, R. Gourlay, J. Vogt, K.M. McMahon, M. Trost, D.A. Lauffenburger, D.J. Lamont, C. Jørgensen, 'Reproducible Automated Phosphopeptide Enrichment using Magnetic TiO2 and Ti-IMAC', Analytical Chemistry (2014) 86(20):10296-302. PMID: 25233145
- C. J. Tape, I.C. Norrie, J.D. Worboys, L. Lim, D.A. Lauffenburger, C. Jørgensen, 'Cell-Specific Labeling Enzymes For Analysis of Cell-Cell Communication in Continuous Co-Culture', Mol. Cell Proteomics (2014) Jul 13(7):1866-76. PMID: 24820872
- C. J. Tape, S.H. Willems, S.L. Dombernowsky, P.L. Stanley, M. Fogarasi, W. Ouwehand, J. McCafferty, G. Murphy, 'Cross-domain inhibition of TACE ectodomain', PNAS (2011) Apr 5;108(14):5578-83. PMID: 21415364