The molecular and circuit underpinnings of repetitive behavior dysfunction — a core symptom of ASD — have remained elusive, but it is assumed that they rely on the same basal ganglia circuits that underlie repetitive behavior control and habit formation. The current project aims to investigate, with unprecedented spatial and temporal resolution, the circuit alterations in the striatum that lead to alterations in spontaneous and learned behavioral sequences in ASD.

Ventola will investigate oxytocin effects on behavioral intervention measures in individuals with autism, assessing neuroimaging, eye tracking and behavioral outcomes.

This project aims to develop computational technologies to model human protein-protein interaction networks that are perturbed in autism.

Crabtree and Gleeson will focus on rare high-impact genetic mutations for factors in the BAF complex to test how links between neuronal activity and the epigenome may be interrupted in ASD.

Hilary Coon’s laboratory aims to further our understanding of the unknown genetic liability in ASD. Coon will provide a comprehensive characterization of whole genome sequence (WGS) data in 1138 Simons Simplex Collection families using novel genetic mutational analyses and behavioral classification measures. By stratifying families/probands into behavioral subsets and using background genetic risk to elucidate new causal WGS risk variants within these subsets, Coon aims to uncover new genetic ASD risk variants.

Stephanie Bielas will use the Asxl3 knockout mouse to assess how alterations in histone H2A ubiquitination influence the transcriptome and cell fate of neural progenitor cells during corticogenesis. These findings will help to unveil mechanisms of dysregulation that lead to autism.

The Noonan lab will systematically identify ASD regulatory networks in the developing brain at high resolution, revealing cellular and developmental mechanisms underlying ASD risk.

Giraldez and Krishnaswamy will combine novel genetic and computational methods to study how mutations in ASD-risk genes affect healthy brain cell development.

Rubenstein will identify how defects in brain development are caused by ASD mutations in Pogz and Suv420h1, genes involved in chromatin remodeling and transcriptional silencing.

Grainne McAlonan plans to use brain imaging methods and out-of-scanner measures to assess responses to arbaclofen, a GABAB receptor agonist, in adults with and without autism spectrum disorder.