Cancer Research Programme
There are currently four major areas of interest:
Lineage specific transcription factors We are using genetic and biochemical approaches to define the molecular mechanisms through which lineage-specific transcriptional regulators orchestrate self-renewal and differentiation, focussing on SOX, FOX and bHLH families. These lie at the heart of cell fate decision-making by neural stem and progenitor cells during development and within brain tumours.
Chemical and genetic screening We are carrying out image-based small molecule screens to search for new agents and pathways that can modulate self-renewal and differentiation of normal and glioblastoma-derived neural stem cells.
Epigenetic programming and reprogramming We are investigating whether changes to the epigenome within glioblastoma-derived cancer stem cells enable suppression of malignant properties. We are using both direct differentiation as well as nuclear reprogramming strategies to test this.
Genome editing Designer transcription factors and nucleases (TALENs or CRISPR/Cas system) provide exciting new possibilities for sophisticated genetic and epigenetic manipulations of mouse and human neural stem cells. We are exploiting these tools with the goal of establishing efficient gene targetting in human neural stem cells and in directing stem cell fate.