Friend or foe? Deciphering the conflicting functions of YAP in breast cancer.

The Hippo/YAP signalling pathway is frequently dysregulated (~80%) in breast cancer. Yet, efforts aimed at targeting this pathway for therapeutic purpose have yielded limited success. This is due in part to the fact that YAP, the pathway’s downstream effector and most amenable target, displays both oncogenic and tumour-suppressing functions depending on cellular contexts. Currently, it is not fully understood when/how YAP exhibits a specific function, and this knowledge gap hampers translation of YAP-directed therapy into clinics. Our data and others have indicated that the specific function of YAP is driven by its ability to form functionally distinct complexes with various transcriptional factors, and such formations are tightly controlled by phosphorylation events. This project employs an integrative systems biology approach combining predictive, network-level mathematical modelling with state-of-the-art experiments to decipher the conflicting functions of YAP in breast cancer, and utilizes that understanding to develop network-level biomarkers that can inform the sensitivity of drugs targeting YAP. Students will work in a highly stimulating and interdisciplinary research environment consisting of both computational and experimental scientists. Students with either excellent computational or experimental background (or both) are encouraged to apply.