Research

Heterocellular Signalling in CRC

The human body contains around 40 trillion cells comprising over 200 different cell types. This complex ‘heterocellularity’ enables metazoan tissues to achieve multiple phenotypes from an isogenic genome. For example, in the human colon, intestinal epithelial cells control nutrient uptake, whereas stromal fibroblasts support epithelial renewal, and tissue-resident macrophages patrol against infection. This multicellular collaboration requires different cell types to communicate.

Like healthy tissue, cancer also contains lots of different cell types. For example, colorectal cancer (CRC) tumours contain mutated epithelial cells, stromal fibroblasts, and multiple immune cells. Each of these cell types contribute to CRC, but the signalling mechanisms underpinning their malignant behaviour are poorly-understood.

The Cell Communication Lab studies how oncogenic mutations (e.g. loss of APC) communicate with stromal and immune cells in CRC. By understanding how mutations regulate all cell types within a tumour, we aim to uncover novel approaches to treat cancer. 

The lab uses cell-specific signalling technologies to measure how oncogenic signals flow through CRC tumours. We measure heterocellular oncogene signalling in biomimetic organoids from genetically engineered mouse models (GEMMs) and clinical patients. You can read more about this approach in our pre-print ‘Single-Cell Signalling Analysis of Heterocellular Organoids’.

You can read more about heterocellular signalling in CRC in our review article for Trends in Cancer 'The Heterocellular Emergence of Colorectal Cancer' and