Research

The laboratory investigates p53-dependent transcriptional programmes to identify genes that mediate tumour suppression beyond canonical cell-cycle control. Using isogenic human cell lines and transcriptomic profiling, the group maps targets whose expression differs with TP53 genotype and explores their consequences for signalling networks such as Hedgehog and mitochondrial metabolism.

Findings from this programme have revealed previously uncharacterised p53-regulated homologues and effectors that connect p53 to pathways controlling metabolism and intercellular signalling. These insights aim to expose actionable vulnerabilities in tumours that retain or lose p53 function.

This programme examines the molecular circuitry that enforces G2/M arrest following DNA damage, with a focus on CDKs and checkpoint kinases. Using genetic knockouts and targeted perturbations, the lab defines which kinases are essential for checkpoint initiation and maintenance, and how their roles vary with p53 status.

Work here clarifies when CDK inhibition can synergise with DNA-damaging therapies, and identifies circumstances under which p53-defective cells rely on alternative checkpoint pathways—information that can inform combination strategies for therapy.

The group explores Chk1 biology using genetic separation-of-function approaches and molecular assays of replication dynamics. By isolating Chk1 activities required for viability from those that regulate checkpoint responses, the programme clarifies the mechanistic basis whereby Chk1 inhibitors exert cytotoxic effects.

These studies inform the rational use of Chk1-targeting agents in combination with DNA-damaging therapies and identify biomarkers that predict sensitivity or resistance to Chk1 pathway modulation.

This programme brings genetic screens, functional genomics and therapeutic tests together to identify how somatic alterations reprogramme tumour-intrinsic innate immunity and influence response to radiation and chemotherapy. The lab uses isogenic models and functional readouts to pinpoint genes and pathways with translational potential.

Integration of genetic findings with imaging and molecular phenotyping aims to prioritise candidates for follow-up in preclinical models and to propose rational combinations with DNA-damaging agents or targeted vectors for therapy.