The primary goal of our research program is to understand how the normal brain becomes epileptic. We seek to understand the cellular and molecular mechanisms behind the development of epilepsy. If these mechanisms can be understood, then new treatments and therapies can be designed to prevent – and ultimately cure – epilepsy.
The hippocampus is a brain region particularly vulnerable to epileptogenic injury, exhibiting extensive pathology and cell loss. In addition, neurons in this region are among the last to be generated in the brain and are one of the few populations of neurons produced throughout childhood and into adulthood in humans. These new neurons are disrupted during epileptogenesis, forming aberrant “short circuits” in the hippocampus that promote seizures.
We are exploring the role of disrupted mTOR signaling in mediating the aberrant integration of abnormal neurons in the hippocampus. Mutations in mTOR signaling pathway genes, such as PTEN, TSC1 and TSC2, cause epilepsy, autism and cognitive dysfunction in humans. Ongoing research in the lab is aimed at understanding how disrupted mTOR signaling promotes the aberrant rewiring of hippocampal neurons, and whether modulating this pathway can be used to prevent and treat epilepsy.