A multitude of brain cancer (glioma) mutations, identified by large-scale next generation sequencing (NGS), are predicted to drive disease through computational algorithms in silico. To investigate whether predicted glioma mutations alter neural stem and/or progenitor cell fate cell (alone or in combination) in intact tissues or organisms, the Brain Cancer Discovery Group uses a combination of Drosophila and human functional genetic models.
Solving mysteries of the neural stem cell niche to understand brain cancer
Gliomas are highly heterogeneous, comprising glioma stem and progenitor cells (GSPCs) embedded within a tumour mass containing glia and neurons. We predict GSPCs drive tumour expansion in response to a combination of internal (cell-intrinsic) cues and external (extrinsic) signals from neighbouring glial cells comprising the bulk of the tumour. Thus, tumour progression will occur, at least in part, as a consequence of defective communication from mutant glia.
We aim to elucidate pathways critical for communication between neural stem and progenitor cells (NSPCs) and their surrounding glial microenvironment, which we know is essential for normal brain development and predicted to be dysregulated in, and fundamental to, glioma initiation and progression. The Drosophila brain provides an excellent model; with the cortex glia microenvironment, or niche, providing neural stem cells (NSCs) with the structural support and secreted signals required for stemness and differentiation. The increased knowledge of the complex cellular genetics underlying glioma cell-cell interactions will enable identification of urgently needed novel therapeutic agents for treatment of primary brain cancer.