Dr. Walsh’s research has focused on the development and function of the human cerebral cortex, and the analysis of genetic diseases that affect the developing brain, resulting in epilepsy, intellectual disability, autism spectrum disorders, and other conditions. His lab has identified dozens of neurological disease genes through world-wide collaborations. He discovered that a few disease genes essential for constructing the human brain were also important targets of the evolutionary processes that shaped the human brain, leading to the founding of the Allen Discovery Center for Human Brain Evolution in 2017, with Professors David Reich and Michael Greenberg. The Center is dedicated to using ancient DNA, human genetics, and cellular neurobiology to understand the parts of the genome that define the unique aspects of the human brain.

Dr. Walsh's lab has more recently pioneered the discovery of somatic mutations—present in some cells but not all brain cells--as important causes of human focal epilepsy, autism, and schizophrenia, as well as developing methods to accurately sequence the genomes of single neurons from human brain. This work has revealed that any given neuron in human brain has hundreds to thousands of mutations relative to the neuron next to it, increasing with age, and in neurodegenerative diseases, despite the fact that neurons do not undergo cell division. These somatic mutations create a mosaic human brain with remarkable genomic diversity.

Dr. Walsh is an elected member of the National Academy of Medicine, the American Academy of Arts and Sciences, and the National Academy of Sciences. He received the UNC-Perl Neuroscience Award and shared the Gruber Neuroscience prize in 2021 and the Kavli Neuroscience Prize in 2022.