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Many brain tumors are initiated by mutations in genes that control cellular metabolism. The altered metabolic state produced by these mutations has broad effects on DNA organization and gene expression. Identifying which of these numerous effects are responsible for causing cells to become cancerous is essential to deepen our understanding of brain tumor biology. Unfortunately, many conventional systems used to study brain cancer in the laboratory are not optimized to address this issue. Employing a variety of genetic engineering techniques, the McBrayer lab has created new systems that accurately model the process of brain cancer initiation and are now using sequencing and computational approaches to reveal the underlying molecular dynamics. They aim to generate new insights into the mechanisms that link altered cellular metabolism with increased brain cancer risk. This information may foster the development of new treatment strategies for brain cancer patients and help maximize the impact of existing therapies.