Molecular Oncology Programme

Genomic Instability Group


Our laboratory has centred its research on trying to understand how cells respond to ‘replicative stress’ (RS), which is frequent in cancer and induced by several anticancer agents. In mammals, RS is suppressed by a signalling cascade initiated by ATR and CHK1 kinases. Throughout the years, our laboratory has developed a wide battery of cellular and animal tools for the study of RS. These tools include mice with enhanced or limited ATR-CHK1 function, cell lines in which the pathway can be activated at will, and chemical inhibitors of the ATR kinase. Our studies have revealed the impact of RS on cancer and ageing, have led to drugs that can be used to test our ideas on cancer therapy, and have also unveiled the mechanisms by which these drugs kill cancer cells. Altogether, our main aim is to understand how genome maintenance is safeguarded – particularly during replication – and to exploit this knowledge as a way to fight against cancer.