Christopher Walsh

Our lab is interested in identifying mutations that disrupt the normal development and function of the human cerebral cortex,  causing autism, epilepsy, intellectual disability and other learning disorders. Not only are these genes vital for the normal development of the cortex, but also some appear to have been altered evolutionarily to allow the unique aspects of the brain that underlie human cognitive abilities.  Therefore these genes define in some sense what makes us uniquely human.  We have already identified more than two-dozen human disease genes. Our genetic work has benefited from worldwide collaborations, especially in Middle Eastern countries where marriage between distant relatives is common, since this enhances the effects of recessive mutations and makes them easier to map and identify.  On the other hand, recent work has focused on somatic mutations that cause just a portion of the brain to be abnormal, typically resulting in epilepsy. We have identified somatic mutations in AKT3, MTOR, and PIK3CA that cause epileptic brain malformations, and we are actively searching for additional somatic mutations causative of neuropsychiatric disorders.  We have also explored the extent to which the genome of one neuron differs from that of other neurons , and found tremendous genomic differences between brain cells.