Development of a pooled cell fitness assay to evaluate pediatric cancer dependencies
Mentor Name: Stephen Mack
Brain tumors are the leading cause of disease-related death in children. To this date treatments for brain tumors remain relatively non-selective consisting of surgery, radiation, and chemotherapy (in some instances). More effective therapies are needed that also spare normal healthy developing tissue. A major challenge towards this goal, is that generally brain tumor models (i.e. cells and mouse models) grow poorly and inconsistently, if at all. This has made it exceedingly difficult to conduct both genetic and drug related testing. Our project attempts to address this challenge by development of a Cell-Based Fitness assays that uses sequencing to track DNA alterations as a surrogate for protein loss-of-function. This assay can be scaled-up to evaluate the contribution of cancer-associated proteins as potentially important molecular targets. We envision that this method will help fill the gap of target evaluation in pediatric brain tumors, which are difficult to grow and manipulate.