Epithelial homeostasis in health and disease
Epithelial tissues are the principal barriers in our body and the source of common diseases, notably cancer and inflammation. The surprising thing is that despite the fact that they are subject to constant bombardment by toxins, infection and transformation, epithelia stay healthy most of the time – and keep us healthy. This is because epithelia possess mechanisms to maintain homeostasis: to detect potential insults and respond appropriately. We believe that a major early-warning system involves changes in mechanical tension upon injury or transformation, that are detected by the neighbouring epithelium, which responds by eliminating the affected cells. These changes in mechanical force are transmitted through cell-cell junctions and detected at those junctions by mechanotransduction. Conversely, events that compromise junctional mechanotransduction can render epithelia vulnerable to disease. Thus, we aim to understand the cellular mechanisms of junctional mechanosensing; determine how they support tissue homeostasis; and test how they are compromised in disease. To do this, we combine cell biology with biophysics, collaborating with developmental biologists, cancer biologists, mathematicians, engineers and physicists.
Traineeships, honours and PhD projects include
- Control of tissue tension by cadherin-cytoskeletal interactions
- Sensing forces at cell-cell junctions: its role in homeostasis and epithelial inflammation.
- Regulation and dysregulation of junctional mechanics: impact for epithelial organisation and tumour invasion.
