New Investigator Grant Awarded to Michael Koldobskiy

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brainstem tumor of childhood with no effective treatment. Although DIPG responds to initial radiation therapy, the tumor inevitably comes back, making it a universally fatal diagnosis. We aim to understand the molecular mechanisms underlying resistance of DIPG to treatment. We study ways in which DIPG cells rely on “epigenetic” modifications, or chemical marks that modify the expression of genes without a change in the genetic sequence itself. We know that DIPG is driven by a genetic change in a key regulator of the epigenome. However, to make progress against DIPG, we need to understand exactly how epigenetic dysregulation drives DIPG resistance. We are studying how variability in epigenetic marks allows DIPG cells flexibility in turning genes on and off. This property enables cellular plasticity and generates heterogeneity among DIPG cells, leading to resistance. By dissecting the mechanisms of epigenetic variability in DIPG, we aim to identify selective vulnerabilities and exploit these for treatment.