The Abdullah laboratory at the University of Pittsburgh is focused on developing novel clinical models of glioma and identifying druggable targets to facilitate early-phase clinical trials. Gliomas are intensely heterogeneous tumors that not only contain numerous cell types but also demonstrate the ability to transition between different phenotypic states. This complexity has made developing model systems that recapitulate human tumor biology both difficult and essential. Traditionally, models of gliomas are two-dimensional cell lines and only represent certain subtypes of the highest-grade glioma, glioblastoma. This is because the unique biology of lower-grade gliomas has prevented them from being studied either outside of the lab or in animals. We have created ex-vivo culture systems that allow us to investigate critical aspects of the tumor microenvironment, immune response, and discover targets for therapy. Our laboratory has previously shown the ability to establish lower-grade glioma organoids in vitro, maintain those cultures for extended periods of time, hibernate, and then reanimate tumor tissue without loss of either genetic or phenotypic fidelity. Our work also includes extensive and sophisticated live-cell imaging analysis that allows for longitudinal, non-invasive assessment of organoid response to treatment. Our organoid model systems, in addition to glioma stem cell and mouse models, allow us to perform highly sophisticated assessments of drug response across platforms and identify rare but critical druggable targets in gliomas. These analyses include complex metabolic tracing and immune cell response assessment. Despite the fundamental principles of genomics, immunology, and cellular cancer biology that underlie our work, our group focuses on projects that have a high potential for immediate clinical translation.