Epithelial signal relay upon injury and tumour initiation

Tissue repair requires coordinated activation of resident stem and inflammatory cells achieved by secreted damage signals. Defects in the repair process can manifest in loss of tissue structure, prolonged inflammation or scarring and predispose for tumour formation. How the damage signal diffusion is regulated, to ensure stem cell activation while preventing excessive inflammation is not well understood. Moreover, it is unclear whether cancer cells can exploit tissue repair signals by altering their diffusion. Therefore, it is important to understand how secreted damage signals are regulated during tissue repair and tumorigenesis. In the proposed study, I will investigate how cell surface glypicans, which control extracellular gradients, interact with damage induced secreted proteins. By using state-of-the-art optogenetic tools I will dissect how glypican-interactions regulate the diffusion of secreted signals to promote tissue repair in vivo. Moreover, by using mouse and organoid models and spatial sequencing approaches, I will compare the roles of extracellular signal relay by glypicans in tumorigenesis and tissue repair. This work will identify how glypicans regulate damage signals and open avenues to generate treatments against the age-associated regenerative decline and tumorigenesis.