The systems biology of oncogenic PI3Kα-driven stemness regulation

Defects in a gene known as PIK3CA are common in breast cancer and in developmental disorders featuring vascular malformations. In these conditions, cells with a PIK3CA mutation are out of tune with their environment and misinterpret the signals they receive. Research suggests that this misinterpretation may result in a loss of cell identity, whereby a cell becomes more 'plastic' and harder to eradicate with conventional therapies. Taking an engineering view, I propose to study the cell as a 'computational system' in order to understand how PIK3CA is wired to regulate cell plasticity, and how this changes according to different conditions - specifically focussing on models of the breast and the vasculature. To succeed, I will collaborate with drug development experts and computer scientists who will teach me how to analyse new types of experimental data that can be used to predict optimal therapeutic strategies for cells with genetic PIK3CA defects.