Investigating the role of the Ubiquitin-Protein Ligase UBR5 in Hedgehog signalling and intestinal tumourigenesis

Using our novel mouse model we have identified an anti-cancer role for a protein called UBR5 in
gastrointestinal tumourigenesis – the third most common cancer in the western world and the
second most common cause of cancer mortality. Based on our novel observations, we hypothesise
that UBR5 acts to restrain cancer initiation through regulating the activity of an intercellular
signalling molecule, called Hedgehog, which in turn controls stem cell behaviour. Stem cells normally
function to maintain and repair a healthy tissue repair, but when deregulated can cause cancer. To
address UBR5’s role in cancer we will examine Hedgehog activity and stem cell function in murine
gastrointestinal tumours produced in control or UBR5-deficient animals. If our hypothesis is correct,
these findings will help initiate screening and translational studies into preventing and combatting
human cancer.