Alterations in intercellular signalling pathways are often the initiating event in carcinogenesis. A prime example being hyperactivation of the Wnt signalling pathway in colon cancer due to loss of function mutations in APC. Cell-to-cell signalling also plays a critical role beyond tumour initiation by allowing cancer cells to reprogram the surrounding tumour microenvironment to promote further tumour growth and metastasis. Such a scenario occurs in prostate cancer, in which tumour cells upregulate and secrete Hedgehog ligands to induce expression of tumour promoting factors in the adjacent stroma.

Given the importance of Wnt and Hedgehog signalling during carcinogenesis, we are interested in teasing apart precisely how both pathways work at the molecular level. A key area of our research is elucidating how the glypican family of extracellular matrix proteins (ECM) regulate Wnt and Hedgehog signalling. A subset of glypicans are frequently misexpressed during carcinogenesis. Establishing precisely how glypicans regulate Wnt and Hedgehog signalling will help us understand how this misexpression helps shape the tumour signalling environment and how this contributes to tumour progression. We are also interested in identifying other ECM components that change during tumorigenesis and investigating what impact this has on the signalling landscape.

To answer these questions the lab uses a combination of imaging, proteomics, molecular biology, CRISPR-Cas9 genome engineering and Drosophila Melanogaster to model tumour formation and progression.