Our lab studies how epithelia maintain a functional barrier and proper cell numbers, despite turning over at high rates by cell death and cell division. We found mechanics control both opposing processes: when cells are too sparse, stretch activates cell division and when too many, crowding activates cell death by ‘epithelial cell extrusion’. While we first discovered extrusion as a process that eliminates dying cells without creating any gaps within the epithelium, we later discovered that most epithelial cells die as a result of live cell extrusion. Due to the significant role extrusion plays in epithelial cell death, a variety of diseases, ranging from bacterial and viral pathogenesis, asthma, and cancer, can result when it is misregulated. Inflammation and infection can result from excess extrusion whereas aberrant basal cell extrusion (back into the tissue epithelia encase) can drive cell invasion and de-differentiation in a class of aggressive tumours. We are currently using organoids and mouse lung slices to investigate the fate of cells that invade by basal extrusion and the signalling that drives this.

PhD students:

• Saranne Mitchell
• Faith Fore
• Lily Gates