- Cell migration and specification in the developing nervous system
- Animal models of human neurodevelopmental disorders
- Pathogenesis of developmental epilepsies
My laboratory is interested in understanding multiple aspects of early nervous system development. A major focus is on the molecular and cellular mechanisms of neuronal migration. Disruptions in migration are associated with a broad range of human disorders including lissencephaly, developmental epilepsies, intellectual disabilities, and autism. We use a combination of in vivo and in vitro methods to investigate the guidance, mechanisms of movement, and genes regulating neuronal migration. Most recently we have been probing animal models with mutations in genes known to result in human migration disorders. Mutations in both LIS1 and ARX give rise to a spectrum of human neurodevelopmental disorders. Using available animal models, and animal models we have developed, along with human tissue, our studies have provided new insights into normal neurodevelopment and the pathogenesis of phenotypes observed in children. Two recent areas of focus include exploring the intracellular signaling and cytoskeletal dynamics required for cell migration and the transcriptional networks required for regulating neuronal migration.
A related area of investigation includes the transcriptional and cell signaling pathways required for neuronal differentiation as it relates to human developmental disorders. We recently identified a novel human intellectual disability susceptibility gene. Using both in vivo and in vitro systems we have defined the role for this gene in BMP signaling and forebrain cholinergic neuron differentiation. We are using this model to test novel, biologically based, treatments for intellectual disabilities.