One of the Horbinski Lab's research interests is the effects of mutant isocitrate dehydrogenase 1 or 2 ("mutant IDH"). Mutant IDH is present in about 30 percent of all diffusely infiltrative gliomas and alters tumor metabolism and DNA/histone methylation. Our group was the first to discover that mutant IDH also suppresses 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, called venous thromboembolism, or VTE. Ongoing efforts in the lab include developing a predictive marker of VTE in glioma patients. We are also studying the effect of Tissue Factor, a procoagulant that is produced at much higher levels in IDH wild-type gliomas than IDH mutant gliomas, on tumor self-renewal.
Our group was the first to demonstrate that the metabolic product of mutant IDH, D-2-hydroxyglutarate, directly stimulates neuronal network activity, which correlates with increased seizure risk in patients whose gliomas contain mutant IDH. Now we are exploring this in cell cultures and mouse models of mutant IDH-induced seizures, in order to develop better ways of controlling seizures in patients with IDH mutant gliomas.
A newer line of investigation in the Horbinski Lab involves meningiomas. These tumors are actually more common than gliomas, grow as solid masses instead of diffusely infiltrating the brain, and exist outside the blood-brain barrier. Despite these features, there currently exist no chemotherapeutic treatments for recurrent and/or high grade meningiomas. Using widely available and new in-house meningioma models, we aim to see whether existing chemotherapies could be repurposed to augment surgery and radiotherapy in high-risk meningiomas.
Dr. Horbinski is director of the Northwestern Nervous System Tumor Bank (NSTB), which collaborates 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, anti-glioma immunotherapy, and targeted nanotherapeutics. The NSTB collects around 350-400 central and peripheral nervous system tumors and matched biofluids per year, distributing fresh, frozen, and paraffin-embedded samples to numerous intramural and extramural investigators. The NSTB also collects gliomas in the postmortem setting, serving as a valuable resource in the study of therapy resistance and patterns of disease spread.
As a board-certified neuropathologist with expertise in molecular diagnostics, Dr. Horbinski is medical director of Neuropathology at Northwestern Memorial Hospital and is active in the 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 greatly improves diagnostic and prognostic accuracy.