Grant: Master's Award: Canada Graduate Research Scholarships - Master's program

Mutations in the Rearranged during Transfection (RET) gene, which encodes a cell surface protein, result in multiple endocrine neoplasia 2 (MEN2), a multi-tumour cancer syndrome characterized by the development of thyroid and adrenal cancers. There are two subtypes of MEN2 which vary in their clinical presentation: MEN2A occurs more frequently whereas MEN2B is more aggressive with an earlier age of onset. The molecular properties of the MEN2 RET mutants that lead to their varying clinical presentations are yet to be clearly elucidated, ultimately leading to knowledge gaps surrounding disease mechanisms. Currently, available treatments for MEN2-related cancers include blocking RET activity, however, drug resistance and unwanted side effects remain persistent problems with their use, underscoring the need for the discovery of novel therapeutic targets. Thus, this project aims to identify differences between the MEN2 RET mutant interactions with proteins involved in downstream signalling pathways that are important for cancer progression. We are using a variety of molecular methods to identify downstream signalling interactions that distinguish MEN2A and MEN2B forms, starting with an unbiased approach to elucidate global differences in protein interactions and signals specific to each mutant form. RET-interacting proteins identified through this work could provide new insights on the natural history of the MEN2 subtypes that could aid in our understanding of the diseases. Finally, candidate interacting proteins identified could also serve as potential therapeutic targets to bypass current drug resistance issues faced with the use of RET-selective inhibitors offering patients therapeutic alternatives.