Brain function and development depend on precise control of gene expression. Thousands of genes must be finely regulated in time and space to achieve proper specialization of brain regions. Moreover, this regulation must be sustained throughout the long lifespan of brain cells, which in many cases is measured in years. Defects in genes affecting this regulation thus, are the basis of a large proportion of brain disease, including, in particular, childhood brain tumors.
Childhood tumors of the brain are lethal and disabling diseases that represent the primary cause of cancer-related death in children in Canada. While overall survival and quality of life have greatly improved for other cancer types such as leukemia, disease outcome has not changed over the last three decades for several brain tumor types. Cure remains a rare exception, and most survivors are left with severe cognitive and neurological deficits. These cancers have a significant impact on both children and their families.
Here, we propose to characterize the expression changes that happen during human brain development, with a particular focus on genes and pathways involved in pediatric brain tumors. Using large-scale datasets profiling gene expression in the human developing brain, and novel datasets we will generate at the single-cell level, we will provide a comprehensive map of gene expression switches that may be altered in childhood brain tumors. We will develop computational methods to integrate this data with a large collection of samples derived from patients. This will allow us to identify developmental pathways altered in these aggressive tumors, which may enable identification of novel targets for therapeutic intervention.