Research

Phosphoinositide 3-kinases (PI3Ks) are central regulators of cellular signalling, controlling cell survival, growth and metabolism. Each isoform has its own tissue distribution, functional role and regulatory mechanism. Our research asks what individual PI3K isoforms actually do, and how those roles change during cancer initiation and progression.

A major focus is the set of activating oncogenic mutations in the pathway that drive tumourigenesis across a wide range of cancers. By working out how these mutations promote uncontrolled proliferation and survival, we aim to identify isoform-selective therapeutic targets that could lead to more effective and less toxic treatment. The work also maps interactions between PI3K and other signalling pathways, which is where much of the complexity of tumour behaviour and therapy resistance lives.

PI3K inhibitors have shown real promise as cancer therapies, but many tumours eventually develop resistance, which limits their long-term effectiveness. Our lab investigates the molecular mechanisms behind that resistance and looks for strategies to overcome it.

We use a combination of cell line models and xenografts to study the regulatory mechanisms involved. That includes identifying secondary mutations in PI3K and its downstream effectors, as well as alterations in other signalling routes that bypass PI3K inhibition altogether. We also test combination therapies aimed at those escape routes, including synergistic drug pairings that may restore inhibitor efficacy and improve patient response.

The tumour suppressor PTEN is the principal brake on the PI3K pathway. Loss of PTEN function, which is common across many cancers, dysregulates lipid signalling and leads to unchecked growth and survival. Our research focuses on the lipidomic changes that follow PTEN loss and how those alterations contribute to tumourigenesis and progression.

Using lipidomic profiling, we track specific changes in lipid metabolism — phosphoinositides, sphingolipids and other membrane-associated lipids — and ask how they affect key cellular processes. We are also testing whether those changes can serve as biomarkers for early diagnosis or prognosis. The work may reveal lipid-based and lipid-regulated targets for therapeutic intervention in PTEN-null cancers.