Our research aims to increase knowledge about the genetic control of brain development and how aberrations in developmental processes lead to neurological disorders including epilepsy, hemiplegia, and autism. Since 2006, the Ess laboratory has focused on tuberous sclerosis complex (TSC) as patients with this disease have prominent brain malformations, white matter disease and a very high prevalence of epilepsy and autism. Resulting from mutations in either the TSC1 or TSC2 genes, this disorder involves dysregulation of the mTORC1 and mTORC2 signaling pathways. This has also led to study of DEPDC5 as this gene also controls mTOR signaling and patients have epilepsy as well as increased risk for SUDEP. Since 2014, we have also been interested in a recently defined disorder, alternating hemiplegia of childhood (AHC), a devastating neurodevelopmental disorder due to mutations in the ATP1A3 gene.
To study abnormal developmental processes in TSC and AHC, we have utilized diverse model systems including transgenic mice, zebrafish, and human induced pluripotent stem cells (iPSCs). Now principally employing iPSCs from patients with TSC or AHC and employing CRISPR/Cas9 modifications, our basic and translational research approaches should culminate in advanced knowledge about pediatric neurological disorders that hopefully lead to the development of novel and more effective therapies.
