Harnessing Viral Mimicry to Target H3K27M-Driven Pediatric Glioma

Midline high-grade glioma (mHGGs) in children frequently contain a H3 lysine-to-methionine mutation (H3K27M) in histone proteins. Dr. Mack and collaborators showed in prior work that H3K27M-driven mHGGs harbor a global re-patterning of histone modification (H3K27me3 loss and subsequent H3K27ac gain). Moreover, this disrupted epigenome activates the expression of endogenous retroviral (ERV) elements. While the role of ERVs in pediatric glioma is poorly characterized, Dr. Mack showed that ERV expression can be amplified by epigenetic therapies to place cells in a state that mimics a viral infection. In light of these highly unexpected and compelling findings, Dr. Mack proposes to 1) Decode the role of DNA hypomethylation in an Olig2-H3F3A:K27M-PDGFRa Driven Allograft Model and 2) Determine the efficacy of DNA methylome priming of H3K27M glioma cells to immunotherapy.