Breast Cancer Functional Genomics Laboratory
Previous and current research
Our laboratory studies human breast cancers (primary tumours and cell lines) using a combination of genomics tools and gene disruption approaches. Our primary interest is in understanding how genetic alterations accumulate, how they determine the biology of cancers, and which cell population within the breast epithelium is targeted by these alterations.
Identification of novel cancer genes: Screening of candidate genes focuses on histone tail modifiers and DNA-damage/repair and mitotic checkpoint pathways. We have identified mutations and expression changes in histone acetylases, deacetylases and methylases. A novel oncogene that encodes a BRCA2-interacting protein, EMSY, has been discovered. Using array-CGH in combination with expression profiling we have now identified several new candidate breast cancer oncogenes and tumour suppressor genes. These are currently being studied in both primary tumours and cell lines.
Functional characterisation of cancer genes: We have used homologous recombination, RNAi and overexpression to characterise the function of candidate breast cancer genes. Using this approach we have recently characterised a gene overexpressed in a subset of ER+ breast cancers. This gene appears to 'connect' the ER-response with an NGF/NF-kB pathway involved in the regulation of apoptosis in breast cancer cells.
Validation of human breast carcinoma prognostic/predictive/therapeutic targets: We analyse tumours where detailed clinical outcomes are available in order to identify molecular classifications that are predictive of outcome and response to therapy. Profiling large numbers of paraffin embedded cancer samples in tissue microarrays is then used to validate molecular markers.
Future projects
The molecular taxonomy of breast cancers has revealed a complexity that suggests that different cancers have different cells of origin. The identification and characterisation of these cancer stem cells and their disrupted pathways will be one of the future research priorities. In parallel we will continue to prospectively validate prognostic and predictive signatures and therapeutic targets.
