Neurophysiology of Excitable Networks Group

Epilepsy affects up to 4% of the population at some time in their lives. There are major challenges in clinical epilepsy care with at least 30% of patients resistant to current therapies. Even among those patients whose seizures are controlled, major issues of drug side-effects and co-morbidities often affect quality of life.

Clinical and geneticist colleagues have discovered more than 30 genes associated with epilepsy with more being discovered each month. However, knowing the genetic cause of epilepsy is not enough to tell you how seizures or epilepsy co-morbidities (e.g. learning difficulties) occur. A mutation in a protein can have its impact on several temporal and spatial scales and understanding the cellular consequence of these changes is central to our understanding, and eventual treatment, of epilepsy.

We use a range of experimental techniques to investigate dysfunction at each of these scales. In particular we use brain-slice electrophysiology methods to directly measure neuronal excitability. We also use state-of-the-art imaging and molecular methods.

Our group’s major recent discoveries have come in understanding the genetic epilepsies. Using mouse models of epilepsy based on human mutations, we’ve identified new disease mechanisms, as well as explaining some of the complexity of the genetic architecture of the epilepsies. Evidence that targeted therapy based on cellular mechanism can be effective in these rodent models exemplifies an exciting paradigm in which precision medicine in the epilepsies can advance.

Our group is also investigating the role of genetic risk factors in sudden unexpected death in epilepsy and has recently provided evidence that variants in major genes that affect heart rhythm can increase risk in susceptible individuals.