Harald Sontheimer, Ph.D.
I. D. Wilson Chair in the College of Science, Virginia Tech
Executive Director, School of Neuroscience, College of Science, Virginia Tech
Commonwealth Eminent Scholar in Cancer Research
Director, Center for Glial Biology in Health, Disease, and Cancer
Professor, Virginia Tech Carilion Research Institute
Glial cells make up half of the brain, yet little is understood about their function. Harald Sontheimer, professor and director of the Glial Biology in Health, Disease, and Cancer Center at the Virginia Tech Carilion Research Institute, is working to learn more.
Sontheimer made foundational discoveries on the functional properties of glial cells in the brain, including the localization and mechanisms of a range of receptors and ion channels that were previously thought to exist only on nerve cells. His work on the fundamental properties of glial cells led to his discovery of a major new therapeutic approach for the treatment of glioblastoma, the deadliest and most prevalent primary brain tumor in humans. He identified a compound called chlorotoxin in scorpion venom, which has the peculiar ability to interact specifically with a protein expressed only on the surface of malignant glial cells. Sontheimer determined that this molecule could prevent the spread of brain tumor cells beyond the original site of malignancy.
In his current research, Sontheimer is focused on developing treatments to extend and improve the quality of life for patients with glioblastomas. These tumors generally cause debilitating injury, often beginning with seizures and leading to progressive cognitive decline and personality changes. The debilitation is caused by the tumor releasing toxic levels of the neurotransmitter glutamate to kill surrounding nerve cells. However, it’s been observed that while many patients experience these symptoms and succumb to the disease within a few months to a year, some patients live much longer and often with only minimal disability. These profound differences were not understood until Sontheimer and his research team discovered that the cause was whether the tumor released glutamate.
The glutamate release occurred through a specific system called the Xc glutamate transporter, which is encoded by the SLC7A11 gene. Patients, who express this gene, on average, die much more quickly from the glioma than patients who do not. Sontheimer mimicked the two discrepant disease outcomes in the laboratory in mice by transplanting tissue from human glioma patients. In the mice with tumors that released glutamate, the gene could be inhibited and the seizures prevented with an available FDA approved drug called sulfasalazine.
Based on these laboratory findings in mice, Sontheimer’s research group conducted a clinical pilot study with nine glioma patients to test the drug’s effectiveness in humans. Just as in the mice, the patients who expressed the SLC7A11 gene had a reduction in glutamate release – and symptoms – when treated with sulfasalazine. An expanded therapeutic clinical study will begin shortly, and Sontheimer will continue to research glial biology and develop possible therapeutic interventions.
Sontheimer earned his doctoral degree in cell biology and biophysics from the University of Heidelberg in 1988. He conducted postdoctoral research at Yale University, where he served as an assistant professor of neurology and neurobiology from 1991 to 1994. Before arriving at the Virginia Tech Carilion Research Institute, Sontheimer was a professor of neurobiology at the University of Alabama at Birmingham.