This project aims to identify molecular switches that can dictate the ability of RAS to contribute to either lung cancer or IPF using 3D culture and proteomics.
Epithelial-mesenchymal transition (EMT) enables the formation of different tissues during embryogenesis, but importantly it is activated in disease-associated process such as organ fibrosis, wound healing and cancer invasion. EMT requires complex orchestration of multiple signalling pathways, including RAS pathway, which has been implicated in lung cancer as well as in IPF. Alveolar Type II (ATII) cells function as stem cells, contributing to alveolar renewal, repair and cancer. Therefore, they are a highly relevant model for studying pathologic EMT, especially considering the high burden of lung diseases, including acute lung injury, lung fibrosis and lung cancer. This project aims to identify molecular switches that can dictate the ability of RAS to contribute to either lung cancer or IPF using 3D culture and proteomics. Specifically, we aim to (i) construct and compare the protein networks in 3D-cultured ATII cells treated with supernatants secreted from IPF-associated fibroblasts or lung cancer-associated fibroblasts in the presence or absence of RAS activation; (ii) assess selected molecules in functional studies using knockout, knockdown, inhibitors and imaging approaches. This project will take place in an active and energetic community of researchers at Southampton of biomedical researchers, bioinformaticians and clinicians, with the support from scientists in the Francis Crick Institute.
Funding: Wessex Medical Research
Funding Duration: 2 October 2017 - 1 October 2019