Targeting Combined Metabolic and Epigenetic Pathways H3K27M DIPG

ONC201 has emerged as one of the most promising therapies for DIPGs. Yet, the precise mechanisms by which ONC201 kills DIPG tumor cells remains to be elucidated. Our research project will investigate how ONC201 simultaneously interrupts energy producing pathways and DNA-associated modifications (called epigenetic modifications) in DIPG tumor cells. We will first carefully dissect out how ONC201 changes metabolism in DIPG tumor mitochondria to alter epigenetic pathways in tumor cells. Then we will try to understand how DIPG tumor cells change their metabolic and epigenetic profiles to escape ONC201 treatment and use this knowledge to provide therapies to overcome ONC201 resistance.