Research

The p53 family comprises multiple proteins and isoforms that can cooperate or antagonise one another. The laboratory identifies p53 interaction partners in melanoma, with particular emphasis on p53/p73 isoforms and the NME and GLI protein families.

Expression profiling, functional interaction studies and patient-derived melanoma material are used to define network states linked to invasion, metastasis and resistance. The long-term goal is to identify combinations of proteins that can serve as biomarkers or therapeutic targets.

Targeted therapy can produce substantial initial responses in metastatic melanoma, but resistant populations frequently emerge. The laboratory examines molecular features that distinguish sensitive, persister and resistant states.

Recent work focuses on p53-family isoforms and microRNAs as regulators of acquired resistance. Comparing paired melanoma models before and after resistance reveals candidate mechanisms that may be targeted to delay or reverse treatment failure.

NME proteins have roles that extend beyond nucleotide metabolism. The laboratory investigates NME1 and NME2 in cell migration, their potential synergistic actions and their movement between cellular compartments after stress.

Live-cell imaging, oligomerisation measurements and functional assays connect protein localisation and assembly with tumour-cell behaviour and DNA-damage responses.

Balkan endemic nephropathy is associated with exposure to aristolochic acid and a high incidence of upper urinary tract urothelial carcinoma. The laboratory has helped define characteristic TP53 mutations and aristolactam–DNA adducts linked to this environmental carcinogen.

This work demonstrates how mutational patterns can connect exposure, mechanism and disease and provides a model for the molecular epidemiology of environmentally driven cancers.