Kevin C. Ess, MD, PhD

Associate Professor of Pediatrics Pediatric Neurology
Gerald M. Fenichel Chair in Neurology Department of Pediatrics
Director Division of Pediatric Neurology

Research in the Ess laboratory is focused on deciphering the molecular mechanisms required for typical 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 study 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. To study these complicated abnormalities of the human brain, members of the Ess lab have generated experimental models of TSC using genetically engineered mice as well as in vitro progenitor cell systems. 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 more efficacious therapies for children who have epilepsy or autism.

To study the control of neural progenitor cell differentiation, we have generated animal models of TSC that inactivate the mouse Tsc1 gene in various progenitor cell populations. These models target dorsal Emx1 progentors or ventral Dlx5/6 progenitors to inactivate the Tsc1 gene in glutamatergic neurons/glia and GABAergic interneurons respectively. In addition to mouse models, we are also generating novel models using human induced pluripotent stem cells to study the role of the TSC genes during differentiation and the production of many neural and non-neural lineages.