Benjamin W. Purow, MD, a professor in the Department of Neurology, was awarded two new R01 grants providing approximately $4 million over the next 5 years to study glioblastoma. He is also co-leading one of the projects in UVA’s recently-awarded $12 million NIH-funded Systems Analysis of Stress-adapted Cancer Organelles (SASCO) Center U54 grant.
Dr. Purow will be using one of the R01 grants to study the vulnerabilities of MMR-deficient glioblastoma. The funding for this project started in August 2022, and will provide approximately $2 million over a 5-year period. Glioblastoma is the most common and aggressive brain cancer, and there is a dire need for new therapeutic approaches. MMR-deficient glioblastoma is a particularly aggressive and treatment-resistant form of this lethal cancer, with extremely high numbers of mutations, and we currently have no effective means to treat it. This grant will support the investigation of two therapeutic strategies that appear to have particular efficacy against MMR-deficient glioblastoma, gaining better understanding of each and aiming to move one or both to the clinic to better treat this devastating form of brain cancer.
Dr. Purow will utilize the other R01 grant to study the novel immunotherapeutic potential of DGKalpha inhibition for glioblastoma. The funding for this project started in December 2022, and also provides nearly $2 million over 5 years. While immunotherapy has led to exciting advances in treating many cancer types, this has not held true for glioblastoma brain cancer. With this new grant, the Purow laboratory will investigate unique ways that inhibiting a protein target called Diacylglycerol kinase-alpha, DGK-alpha, can be applied alone and alongside other therapies to more successfully drive an effective immune response against this dreaded cancer.
In addition to the two newly secured R01 grants, Dr. Purow, along with Matt Lazzara, PhD, professor of Chemical Engineering & Biomedical Engineering, and Kristen Naegle, PhD, associate professor of Biomedical Engineering, is co-leading one of the projects in UVA’s recently-awarded $12 million NIH-funded Systems Analysis of Stress-adapted Cancer Organelles (SASCO) Center U54 grant. Approximately $600 thousand of the $12 million grant will be utilized in the Purow laboratory over a period of 5 years to study EGFR signaling network adaptations to overcome RAS-induced membrane stress in glioblastoma. In particular, the team will try to understand the signaling mechanisms by which glioblastoma cells avoid a form of cell death termed methuosis—“drinking themselves to death.” This could lead not only to new understanding of glioblastoma biology but also to new therapeutic approaches.
Learn more about Project 3. EGFR signaling network adaptations to overcome RAS-induced membrane stress in glioblastoma at the Center for Systems Analysis of Stress-adapted Cancer Organelles (SASCO).