My laboratory investigates how cancer develops and how the disease changes over time. I am particularly interested in how patterns of DNA damage shape the biology of cancer.
Our genome is vulnerable to many types of damage and it exists in a constant state of repair. We use a variety of discovery systems to study DNA repair. This includes working with rare individuals in which DNA repair mechanisms break down, as they help us understand the connection between DNA damage and disease.
We model DNA damage processes in the laboratory to investigate fundamental blue sky research questions, such as, how does DNA damage contribute to ageing? We also look to apply our research, by investigating new ways to target cancers with altered DNA repair capacity. Most recently our group has been investigating how common drugs used to treat cancer or viral infections impact on our genome.
Our mission is to understand how DNA damage impacts our health. We aim to leverage this knowledge to improve outcomes for cancer patients, by providing new ways to aid detection and by delivering treatments to short-circuit the disease process.
Our major disease focus is on leukaemia, a cancer of the blood system. We are defining genes that contribute to the development of leukaemia, and studying factors that influence a patient’s response to therapy.
My research team has used genomics to reveal the cause of familial cancer syndromes, identify novel fusion oncogenes and define therapy response biomarkers. Our group develops analytical tools to explore how cancers change over time in response to treatment.
The link between DNA damage and cancer is well established, but there is growing evidence of a contribute to other diseases. This project aims to accelerate the natural decay of the genome to determine how somatic mutations contribute to ageing and disease. We will manipulate DNA repair pathways in model systems to stimulate diverse forms of DNA damage and track their influence. We will go on to study how real-world stresses, like cancer therapy or chronic inflammation modify patterns of clonal selection.
Cytidine deaminases from the APOBEC-family make a major contribution to the mutational landscape of cancers from the bladder, breast and lung. These enzymes play a key role in viral defence, but often become misdirected and can trigger thousands of mutations in cellular DNA. We are investigating how APOBEC activity is regulated, how damage from these enzymes triggers cancer and how best to treat cancers with high levels of APOBEC.
Many antiviral therapies target DNA or RNA synthesis to disrupt viral replication. It is exceedingly difficult to target such fundamental biological processes without causing collateral damage. This project will survey DNA damage from antiviral therapies, both in normal tissues and in cancers, to reveal genetic factors, transcriptional states and drug interactions that modify their impact.
Our laboratory has expertise that spans genetics, genomics, bioinformatics, haematology and cancer biology. We collaborate broadly and assemble expert teams to attack challenging questions.