Research programme 01
Mutation-specific TP53 biology and tumour evolution
We define how individual TP53 mutations and p53 isoforms produce distinct effects on genome stability, metabolism, invasion and patient outcome.
Central question
How do specific TP53 alleles and isoforms reprogramme cancer cells in ways that differ from simple loss of p53?
TP53 is frequently treated as a single altered pathway, yet different missense, splice-site and isoform states can generate markedly different biological consequences. The laboratory combines pan-cancer analysis with experimentally defined models to distinguish loss of tumour-suppressive activity from dominant-negative and gain-of-function phenotypes.
Recent work has shown that mutations at codon 179 can drive lipid accumulation and invasive behaviour, while splice-site mutations form biologically and clinically distinct groups with variable effects on TP53 expression, genomic instability and relapse. The programme also examines how alternative p53 transcripts and protein isoforms modify prognosis and therapy response.
Approaches
- Isogenic and engineered cancer-cell models
- CRISPR-Cas9 genome editing
- Targeted and next-generation sequencing
- Transcriptomic and splice-variant analysis
- Metabolic and lipid-phenotype assays
- Invasion, migration and survival studies
Selected work
- TP53 mutation at codon 179 metabolically reprograms cancer cells to promote invasion (2026)
- TP53 Splice Mutations Have Tumour-Independent Effects on Genomic Stability and Prognosis (2025)
- Combining TP53 mutation and isoform has the potential to improve clinical practice (2024)