More than half of the genes associated with autism spectrum disorders (ASDs) encode for regulatory proteins. In the current project, Kasper Lage’s team aims to unravel the regulatory networks of transcription factors TCF4, CHD8, DYRK1A and GIGYF1 in human induced pluripotent stem cell (iPSC)-derived glutamatergic excitatory neurons using newly developed genome-wide chromatin-binding profiling methods. They then plan to use integrative computational methods to associate the identified regulatory networks with ASD genome-wide association studies and exome sequencing data to identify the subnetworks and sets of target genes most enriched in ASDs.

Mark Zylka plans to evaluate the extent to which molecular phenotypes worsen with age in Chd8^V986*/+ heterozygous mice, which harbor a loss-of-function autism-linked mutation. Results from this study are expected to highlight the importance of expanding the age range over which autism model mice are evaluated, with the ultimate aim of better understanding neuropathological changes in older individuals with ASD.