My laboratory focuses on gene expression, and how misregulation can contribute to disorders including autism, epilepsy, and cognitive and behavioral dysfunction. Our goals are to identify genes that are inappropriately expressed, either in amount, location or developmental timeframe within neurodevelopmental disorders. This will allow us to directly characterize the consequences of misexpression at the cellular and organismal level, and will highlight pathways critical to the development of these disorders that may be impaired in other individuals, leading to the identification of additional genetic defects, and to novel or more specific treatment options.
A specific interest in our lab is investigating genes that are imprinted, an epigenetic phenomenon whereby a gene is expressed only from the chromosome inherited from either the mother or the father. The gene for Angelman syndrome, for example, is only expressed from maternal chromosome 15 in neurons. As a result, different phenotypes result if genes are deleted, mutated or otherwise altered on a maternal ch15 vs. a paternal ch15. Proper regulation of imprinted genes is mediated by proteins such as MeCP2, which is mutated in Rett syndrome. The overlap between autism, Rett syndrome and Angelman syndrome may be due to the interplay between MeCP2 and the regulation of ch15 imprinted gene expression levels. We are using both patient samples and rodent models to determine the effects of genetic or environmental insults on the expression patterns of imprinted genes. We are also developing RNAi-based mouse models to analyze the social and behavioral effects of aberrant expression of autism candidate genes.