New Investigator Grant Awarded to Stephen Mack

Diffuse intrinsic pontine glioma (DIPG) remains a universally fatal disease. Treatment consists of radiotherapy, which may alleviate patient symptoms, but ultimately is not curative. Our understanding of the genetic basis of DIPG has improved substantially in the last decade however these findings have led to only a handful of potential therapies currently being tested in clinical trials. Novel and rationale approaches are desperately needed to devise effective, safe, and durable treatments for patients with DIPG. Towards this goal, our lab recently found that DIPG patient tumors which commonly harbor a H3K27M mutation express high levels of viral sequences normally silent in non-malignant cells. Importantly, we show that viral element expression can be exacerbated by specific drugs categorized as epigenetic therapies. My proposal seeks to understand the functional contribution and regulation of these viral elements to DIPG biology. I anticipate that these findings will delineate the mechanisms that activate viral sequence expression, the ways cells respond, and new pathways that may be leveraged to treat DIPG patients.