Normal development and cancer

My research is focused on the connection between normal development and cancer.

It is designed to test the central hypothesis that cancers arise in children and adults as an aberrance of development, driven by biology that encompasses the parental cell lineage of each tumour, and that renders the malignant tissue vulnerable to therapeutic attack. Research in my laboratory is organised into three programmes, founded on key sequential observations.

Programme 1 studies the origins and treatment of childhood brain tumours that kill more children than any other cancer.

Over the last five years we have identified major regulatory mechanisms that govern the development and maintenance of clinically relevant subtypes of childhood medulloblastoma, ependymoma and choroid plexus carcinoma, unmasking new treatment approaches.

Over the next five years we will deploy this knowledge, engaging international CRUK and NCI-funded research consortia that I have established, lead and/or participate in, to develop novel diagnostics and treatments. These new treatments will be designed to reduce dependency on conventional therapy that permanently damage survivors.

Programme 2 extends our work in the developing brain to identify factors that govern cancer risk across all organs and ages.

This Programme has provided the first functional, organism-wide evidence that cancer risk is dictated by the complex interaction of stem cell capacity, tissue development and damage.

Over the next five years Programme 2 will analyse our extensive multimodal datasets of normal and malignant tissues to unmask and validate fundamental regulators of cancer risk.

We will use holistic, agnostic, deep-learning approaches for these 'big data' studies, with the goal of developing new cancer treatment and prevention approaches.

Finally, Programme 3 is investigating developmental processes that underpin metastasis–the principal cause of cancer-related death.

We have identified a single ion channel NALCN, as a key regulator of epithelial cell trafficking from both normal and malignant tissues, thereby divorcing metastasis from upstream tumourigenesis and unmasking an oncogene-independent metastatic pathway.

Over the next five years, Programme 3 will investigate further how NALCN regulates epithelial cell trafficking into the circulation, and collaborate with colleagues across the CRUK network and in industry (in part supported by CRUK Partnership seed funding) to determine if NALCN is an anti-metastatic therapeutic target.

My overarching goal is to deploy the knowledge acquired through our research to extend and improve the lives of children and adults with cancer–bringing forward the day when all cancers are cured.