The main focus of Dr. Horbinski's research laboratory is on the effects of altered glioma metabolism in the microenvironment. Mutations in isocitrate dehydrogenase 1 or 2 (mutant IDH1/2) are present in a large proportion of gliomas, and are known to alter tumor metabolism and DNA methylation. Dr. Horbinski was the first to discover that these mutations also suppress thrombosis (blood clots), both within the tumor and throughout the patient. This has profound implications for what the tumor looks like surgically and under the microscope, and predicts which brain tumor patients are at risk for potentially life-threatening blood clots.
Our group was also the first to demonstrate that the metabolic product of mutant IDH1, D-2-hydroxyglutarate, directly stimulates neuronal network activity, which correlates with increased seizure risk in patients whose gliomas contain mutant IDH1.
In addition to primary gliomas, Dr. Horbinski also employs animal models of metastatic cancer using patient-derived xenografted tumor tissues. These models nicely recapitulate most of the key histologic and clinical features of metastatic carcinomas, making them ideal platforms in which to evaluate novel anti-metastatic therapies.
Dr. Horbinski and the NSTB collaborate with many investigators on a wide range of brain tumor projects, including groundbreaking work involving epigenomic regulation of pediatric and adult gliomas, cell signaling and stem-like properties, personalized anti-glioma vaccines, and targeted nanotherapeutics. The NSTB collects around 350 central and peripheral nervous system tumors and matched biofluids per year, distributing fresh, frozen, and paraffin-embedded samples to numerous intramural and extramural investigators.
As a board-certified neuropathologist with expertise in molecular diagnostics, Dr. Horbinski is spearheading the expansion of molecular testing of brain tumors for clinical and research applications. A key point of emphasis is the implementation of next generation sequencing-based profiling of pediatric and adult tumors, which has been shown to greatly improve diagnostic and prognostic accuracy.