DNA Repair Gene Dysfunction
We are now looking to address the mechanism by which BRCA2 mutations and dysfunction leads to genetic instability within primary prostate epithelium. Using a combination of primary human epithelial cultures and murine genetically modified mice, we are determining the relationship between BRCA2 mutation knock-in or nullizygous BRCA2 knock-out, in combination with pertinent mutated oncogenes and tumour suppressor genes, in a series of genotype-phenotype studies. Phenotypes to be investigated will include different inter- and intracellular signalling, differential DNA repair and genomic stability and affects on androgen signalling.