Translational Neuro-Oncology Laboratory

The Laboratory for Translational Neuro-Oncology at the UPMC Hillman Cancer Center, under the direction of Kalil Abdullah, MD, is focused on developing novel clinical models of glioma and identifying druggable targets to facilitate early phase clinical trials. 

Gliomas are intensely heterogenous 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 2-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. Ex-vivo culture systems have been created allowing researchers to investigate critical aspects of the tumor microenvironment, immune response, and discover targets for therapy. The 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. This work also includes extensive and sophisticated live-cell imaging analysis that allows for longitudinal, non-invasive assessment of organoid response to treatment. 

Gliomas across the malignancy continuum

Figure legend: Gliomas across the malignancy continuum are presented after extended culture. These organoid cultures are minimally processed and come directly from brain tumor resections, allowing for maintenance of the cytoarchitecture and microenvironmental components of the original tumors (Abdullah et al, Neuro-Oncology 2021).

The organoid model systems, in addition to glioma stem cell and mouse models, allows researchers 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 this work, the Translational Neuro-Oncology lab group focuses on projects that have high potential for immediate clinical translation. To that end, they maintain active collaboration with other laboratories and pharmaceutical companies worldwide. Because of the nature of their research, a close interplay between the neurosurgical operating room and the laboratory is paramount. As such, they have an expansive team of highly motivated scientists and clinical research coordinators that facilitate tissue acquisition, processing and analysis. 

Over the past year, the lab has demonstrated several key findings. They have demonstrated the first known ex vivo models of low-grade glioma that could be reliably reproduced and demonstrated faithful reproduction of the glioma microenvironment when compared to matched parental tumors (Abdullah et al, Neuro-Oncology, 2021). Then, to develop a method to assess these surgically explanted organoids (SXOs), they used rapid live-cell microscopy to noninvasively assess tissue response to treatment which rivaled traditional immunohistochemical methods (Buehler et al, Cancer Informatics, 2021). Finally, with collaborators from Duke University, Translational Neuro-Oncology lab researchers have evaluated an exciting preclinical compound that induces telomeric damage in high grade gliomas that is being developed for use in clinical trials (Yu et al, Clinical Cancer Research, 2021).