Angharad Wilkie’s interest in molecular biology and cancer research began while studying for her undergraduate degree in Biomedical Science at Bangor University.
Lectures on cancer biology delivered by NWCR-funded researchers sparked an interest in the field, which developed further when she undertook her dissertation project in Dr Rita Cha’s laboratory at the NWCR Institute. She later undertook an internship as a laboratory assistant at the Institute to further enhance her research skills in preparation for a future in cancer research. In 2015, Angharad was accepted for an NWCR-funded studentship, and she was very excited to join Dr Chris Staples’ newly-formed group in Bangor.
Her research centres around the primary cilium; an antenna-like organelle that acts as a crucial signalling hub for certain signalling pathways, some of which may promote therapeutic resistance. Although cilia are often absent from cancer cells certain chemotherapies can temporarily cause ciliary reformation. One of Angharads core aims is to determine whether this reformation alters cancer cell drug sensitivity.
Furthermore, defects in cilium formation result in ciliopathies, genetic diseases with a diverse spectrum of symptoms ranging from the relatively mild to embryonic lethal. Interestingly, there are emerging links between cilium formation and aspects of the DNA damage response (DDR). Most notable among these links is the finding that mutations in several DNA repair proteins can cause human ciliopathies.
In a screen for novel regulators of genome stability the giant ubiquitin ligase HERC2 was identified and it was subsequently shown that HERC2 not only prevents accumulation of endogenous DNA damage but also facilitates ciliogenesis. Angharad also hopes to identify the relevant substrates and interactors of HERC2, and clarify the consequences of its loss for the ciliogenesis machinery. This may be of clinical relevance in lung cancers, where low expression of HERC2 is associated with decreased survival.