My research group has a number of interests involving cancer, developmental biology, biochemistry, cell biology and molecular biology. A major focus of the lab is to understand how genes expressed at specific stages of retinal development are regulated. Towards this end, we are characterizing genes whose expression profiles suggest a role in the commitment and differentiation of retinal precursor cells. Using the chick retina as our model system, we are carrying out chromatin immunoprecipitation (ChIP) and in ovo electroporation experiments to understand the role that the transcription factor AP-2 plays in retinal differentiation.

Another focus of the lab is to understand how retinoblastoma, a childhood tumour of the retina, differs from normal retinal cells. Using a differential screening approach, we have identified a novel member of the DEAD box protein family, called ‘DEAD box 1’ or DDX1. DDX1 is believed to unwind double-stranded RNA and to play a role in the processing of RNAs. We have discovered that DDX1 is amplified and over-expressed in retinoblastoma as well as in another childhood tumour called neuroblastoma. We propose that over-expression of DDX1 in these tumours provides a growth advantage. We are using DNA transfections, confocal microscopy, transgenic mice and biochemical assays to determine the function of DDX1 in both normal and cancer cells.

A third focus of the lab is to identify and characterize glial differentiation genes that are expressed in brain tumours called malignant gliomas. We have discovered that brain fatty acid-binding protein (B-FABP), a marker of radial glial differentiation, is co-expressed with glial fibrillary acidic protein (GFAP), another marker of glial cell differentiation, in malignant glioma tumour cells. Our goals are to determine how the expression of glial cell differentiation markers (e.g. B-FABP and GFAP) is regulated in malignant glioma tumour cells and to study the function of these genes in malignant glioma cells. We believe that a better understanding of these glial differentiation genes will provide insight into how to treat malignant glioma tumours, by inducing their terminal differentiation. We are using microchip cDNA arrays, cell invasion and motility assays, transformation assays, as well as a variety of assays related to the regulation of gene expression, to understand how the expression of glial genes affects the growth properties of malignant glioma cells.