Brain tumours, the most common solid malignancies of childhood, differ from other solid malignancies in that brain tumours rarely metastasize outside of the central nervous system. Despite this relatively "restricted" pattern of progression, metastatic brain tumours are therapy resistant. Due to the devastating growth and neurocognitive consequences of the best current treatment which includes radiation, there is much interest in identifying molecular pathways that specify metastatic behaviour in malignant paediatric brain tumours, in order to ultimately develop more effective and less toxic tumour therapy..
Our lab is interested in cellular and molecular mechanisms that underlie tumour progression in central nervous system primitive neuroectodermal tumours (PNET), the most frequent group of paediatric malignant brain tumours. Current projects involve use of high resolution genomic tools such as SNP microarrays and ChiP-on-chip technology to define novel genes and pathways associated with aggressive PNET phenotypes.
A major interest in the lab is to determine how c-Myc, a potent oncoprotein, specifies aggressive phenotypes in cerebellar PNET/medulloblastoma. To investigate the molecular basis of this association we have focused on identifying Myc protein interactors and target genes with key contributions to Myc-mediated transformation in medulloblastoma cells. Recently we identified a novel family of Myc interacting and co-transforming proteins, the JPO proteins, which are overexpressed in metastatic medulloblastoma. Characterization of the role of JPO proteins and other novel Myc partners/targets in medulloblastoma/PNET pathogenesis is the focus of ongoing work.