Research in my laboratory is focused on deciphering the molecular mechanisms required for normal brain development and how disruptions of these processes lead to malformations of the cerebral cortex. Children with such aberrations typically suffer from severe seizure disorders (epilepsy) as well as severe cognitive and behavioral problems such as autism. To approach these complex neurologic disorders, we have been studying tuberous sclerosis complex (TSC), a disease that prominently features cortical malformations and is caused by loss of either the TSC1 or TSC2 genes. TSC is quite prevalent and is the most common genetic cause of seizures and autism in children. Our previous investigations led us to hypothesize that the TSC1/2 genes are essential for neural progenitor cell function able to impact the differentiation and migration of neurons and glia. Abnormalities of these developmental processes may cause the cortical malformations in TSC that underlie epilepsy as well as autism in these patients. To study these complicated abnormalities of the human brain, we have generated experimental models of TSC using genetically engineered mice and zebrafish as well as in vitro progenitor cell systems including patient-derived induced pluripotent stem cells (iPSCs). The ability to manipulate Tsc1 or Tsc2 gene expression in mouse or human progenitor cells allows us to determine the role of these genes during neuronal and glial cell specification, differentiation, and migration. Our long term goal is to use these models to precisely define the molecular pathways used by the TSC1/2 genes during human brain development. This knowledge will facilitate the development of rational and hopefully more efficacious therapies for children who suffer from epilepsy or autism.