New Fralin Biomedical Research Institute laboratory to explore genetic prelude to epilepsy
Led by Associate Professor Matthew Weston, the new research team will study how genetic changes alter protein function and electrical signaling in the brain, triggering seizure disorders in children.
Childhood epilepsy is a disorder of repeated seizures that affects about 1 percent of children. It is the most frequent chronic neurologic condition in childhood, and genetic factors underlie the disease in more than a third of these patients.
The Fralin Biomedical Research Institute at VTC recently recruited neuroscientist Matthew Weston to investigate this seizure activity, particularly how specific genetic variants that cause childhood epilepsy regulate brain activity.
“Some of these children have dozens of seizures a week, which significantly impacts their quality of life and can impair neurological development,” Weston said. “We’re examining the genes, cells, and critical time points of development that influence synaptic changes underlying epilepsy to find new, targeted therapeutic approaches for epilepsy.”
Weston’s laboratory, slated to open in August, studies a handful of genes that encode proteins to regulate healthy brain function. Abnormal protein levels or impaired function can trigger uncontrolled electrical disturbances in the brain.
“Hundreds of genes can give rise to some of these childhood seizure disorders, but we focus on ones that largely effect synaptic transmission or neuro-excitability,” said Weston, who also holds an appointment in Virginia Tech's College of Science in its School of Neuroscience.
His laboratory studies one gene that encodes a potassium ion channel protein. These important molecular structures allow potassium to enter and exit neurons. The research team focuses on a rare mutation in this gene, KCNT1, that allows too much potassium to flow outward through the channels, particularly in a certain type of cell – the brain’s inhibitory neurons - causing severe seizures in children.
Weston’s team described in Cell Reports how this mutation impairs the function of these inhibitory neurons in the cerebral cortex, reducing their ability to brake and refine electrical activity in the brain. Seizures occur when these inhibitory cells can’t slow neuronal firing.
The research team also examines a gene that encodes a molecule, dynamin, that brain cells use to shuttle signaling chemicals across the synaptic gap between two neurons. Weston and his collaborators at Columbia University recently found that this variation also appears to impair inhibitory neurons, resulting in hyperactivity.
The laboratory also investigates how two complexes of a protein, mTOR, influence brain cell proliferation, growth, migration, connectivity, and cell death. In 2020, Weston and his team published a paper in eLife about how mTOR may be involved in neurological diseases.
His research is funded by three grants from the National Institute of Neurological Disorders and Stroke to study mTOR hyperactivation, dynamin, and epilepsy.
Previously an assistant professor at the University of Vermont School of Medicine, Weston completed his undergraduate degree at the University of Virginia and his doctoral degree in neuroscience and postdoctoral training at the Baylor College of Medicine at the Texas Medical Center in Houston.
Weston has received a Pathway to Independence Award and a fellowship training grant from the National Institute of Neurological Disorders and Stroke. He also was awarded a postdoctoral research fellowship by the Epilepsy Foundation.
He has begun recruiting to fill postdoctoral associate, research technician, and graduate student roles in this lab.
