Our Research
Our lab is focused on understanding the role of extracellular matrix (ECM) internalisation in cancer. The ECM is a complex network of secreted proteins, such as collagens, laminins and fibronectin, which, besides providing support for tissues and organs, also plays an active role in controlling a variety of cellular processes, including cell migration, proliferation and oncogenic transformation. Our recent data indicate that the internalisation of ECM components is strongly upregulated in invasive cancer cells, compared to normal epithelial cells and non-invasive cancer cells, suggesting that ECM uptake might be involved in controlling invasive cell migration. Furthermore, we also found that ECM endocytosis is able to sustain cancer cell growth in nutrient-deprived conditions, raising the intriguing hypothesis that the ECM could represent a source of food for starved cancer cells. We are currently addressing 3 main research questions:
How is ECM internalisation regulated? We are investigating which ECM components are preferentially internalised by cancer cells (using a mass spectrometry approach, in collaboration with Dr Mark Collins at the University of Sheffield), the role of the ECM receptors of the integrin family in controlling ECM uptake and we will use a functional genomic approach (in collaboration with Dr Fred Bard, IMBC A*STAR institute in Singapore) to unravel novel regulators of ECM endocytosis. We have developed an imaging-based approach to visualise and quantify the internalisation of simple and complex 3D matrices, such as collagens, matrigel and fibroblast-generated cell-derived matrices.
How does ECM uptake and remodelling contribute to cell migration? We use live cell imaging to measure cancer cell invasion and migration under circumstances where the internalisation of ECM components is inhibited. In addition, we developed 3D systems and we are using fly (in collaboration with Dr Kyra Campbell) and Zebrafish (in collaboration with Dr Freek van Eeden) in vivo models
How does ECM uptake impinge on cell metabolism? We use a metabolomic approach (in collaboration with Dr Heather Walker at the University of Sheffield) to elucidate how the internalisation and degradation of ECM components affect cancer cell metabolism under nutrient starvation.
We are part of the ECM and stroma interest group at the University of Sheffield. You can find more information here:
https://sites.google.com/sheffield.ac.uk/ecm-stroma/home?authuser=0