H3.3K27M-altered pediatric diffuse midline glioma (DMG) are fatal brain tumors, accounting for 10% of pediatric brain tumors and affecting young children between the median ages of 5-10 years old. Despite advances in surgical resection, radiation, and chemotherapy, there remains no effective curative option. There is an unmet clinical need to develop new and effective therapies for DMG. The majority of DMGs are driven by mutated histone proteins known as H3.3K27M oncohistones. When H3.3K27M oncohistones are incorporated onto chromatin, they cause genes to be inappropriately transcribed and the production of pro-tumorigenic proteins, but also paradoxically of anti-tumorigenic proteins derived from viral relics in the human genome. My research leverages this susceptibility and explores a novel way to treat DMG using an emerging therapeutic approach called “viral mimicry” to induce virus reactivation. In this process, tumor cells are tricked into thinking they are infected with a virus which prompts the immune system to mount an antiviral response against the tumor causing tumor cell eradication. Using drugs that promote viral mimicry may therefore constitute a new and effective treatment modality for DMG patients.