Project 453072

Pluripotent stem cells have the potential to become any cell type in an adult organism including nerve cells. SOX2 is a critical gene in stem cells and is also required for normal brain development and nerve cell regeneration. SOX2 is also frequently overexpressed in cancer and associated with poor patient outcome. Mutations outside the SOX2 gene, in specialized DNA sequences called enhancers, can influence when and where the SOX2 gene is turned on in the brain. This aberrant expression of SOX2 can lead to altered brain function and, in severe cases, infant death due to brain malformation. Our research team recently discovered enhancer sequences that turn on the SOX2 gene in stem cells and showed that these sequences influence the function of neural stem cells and have links with neurological disease. Our current proposal will determine the mechanisms through which SOX2 gene expression is modulated in neurological diseases. This will allow us to better understand why some people develop neurological disease to improve disease diagnosis and treatment using precision medicine approaches.