Our laboratory uses cell line and patient-derived models of brain tumors cultured in vitro or grown in mice to study therapy resistance. We use steady-state and stable-isotope tracing metabolomics to interrogate metabolic abnormalities in these models, which we then perturb genetically and pharmacologically to determine the relationships that link abnormal metabolism to therapy resistance as well as the mechanisms behind these relationships. We have a particular focus on purine metabolism and are working to measure the activity of this pathway and inhibit it in patients with brain tumors.