The most frequently diagnosed cancer is skin cancer. Mechanical features of the tissue microenvironment are crucial players in the regulation of normal skin regeneration and in skin carcinogenesis. The mechanosensor Yes-associated protein (YAP) plays a key role in translating external mechanical stimuli into regenerative responses. Dr Beverdam developed the viable YAP2-5SA-?C mouse line that exhibits increased YAP activity in the epidermis resulting in severe hyperplasia and dermal fibrosis. Dr Beverdam also found that epidermal YAP activates Wnt/?-catenin, ROCK, and Shh/GLI2 signalling to promote fibroblast activation and dermal fibrosis. These pathways all play key roles in carcinogenesis of the skin and of other tissues. In this project, the Scientia scholar will employ complex mouse genetics, advanced 2D and 3D imaging technology and pioneering approaches to measure tissue biomechanical properties to elucidate the mechanisms activated by epidermal YAP that promote Wnt/?-catenin, ROCK, and Shh/GLI2 mechanosignalling during normal skin regeneration, and how this is perturbed in skin carcinogenesis in mouse and man. Outcomes will open up innovative therapeutic avenues to treat skin cancer and other epithelial cancers displaying increased YAP activity.
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St George and Sutherland Clinical School
St Vincent's Clinical School