Stessman aims to use human cell lines engineered to express patient mutations to determine how these genes contribute to disease etiology, particularly during early development of the human brain. These cell lines will also be a useful tool for therapeutic development in the future.

Gabel will utilize mouse models to explore how ASD-associated mutations in DNMT3A alter DNA methylation in the brain and drive ASD pathology.

Ellis and Martinez-Trujillo will explore the effects of SHANK2 mutations on protein translation and network connectivity in iPSC derived neurons.

Blencowe will identify and characterize small molecules to rescue activity-dependent neuronal microexon splicing, providing a potential therapeutic strategy for autism.

Dysregulation of glutamatergic neurotransmission is believed to contribute to the development of autism spectrum disorder (ASD). Bruce Herring’s laboratory recently identified a hotspot of ASD-related de novo mutations in the glutamatergic synapse regulatory protein Trio. Herring’s team now aims to precisely characterize the impact these ASD-related Trio mutations have on glutamatergic synapse function and behavior.

Zhang aims to provide an atomic resolution structure of the Shank3:CaMKIIα complex and to understand the functional effects of activity and Shank3 ASD mutations on this complex.

Panagiotakos and her lab will use the 16p11.2 mouse model to explore how alternations in calcium signaling influence the function of neural stem cells and contribute to disease phenotypes.