Our project is a proof-of-concept study to determine differences in the phosphorylation status of proteins in different striatal cell types in a novel mouse model of the Okur-Chung neurodevelopmental syndrome that is driven by a mutation in the kinase CK2. The aim is to ascertain if master signal transduction pathways can be identified that are differentially regulated in specific neuron types, which is of crucial importance when developing novel therapeutical approaches for ASD.

Autism can be caused by dysregulated gene expression during development. In the current project, Reza Kalhor plans to create in vivo longitudinal recordings of target gene expression as the mouse brain develops in a series of increasingly complex differentiation and patterning events. Gene expression changes in neurotypical and mouse models of autism will be compared to aid in our understanding of how the foundation for autism phenotype is laid during embryogenesis.

Excessive activity of UBE3A, an E3 ubiquitin ligase, is linked to a prevalent form of autism. The current proposal will analyze genetic variants in UBE3A to develop peptide inhibitors that can inhibit its enzymatic activity.

Matthew MacDonald, Bernie Devlin and Kathryn Roeder plan to leverage the most recent genomic results and integrate them with a wealth of high-quality proteome and transcriptome data to achieve a deeper understanding of how different classes of genetic susceptibility and different ASD risk genes converge on overlapping biological networks critical to ASD.

The overall goal of Xin Tang’s project is to yield insights into the molecular programs that lead to reduced KCC2 gene expression in neurons from individuals with autism and to consequently develop mechanism-guided drugs that restore KCC2 gene expression and ultimately reverse symptoms of the condition.

Defining how epigenetic modification of chromatin regulates neural stem cell proliferation is relevant to understanding the brain overgrowth exhibited by a proportion of people with ASD. Here, Michael Piper’s goal is to understand how the epigenetic landscape regulates transcriptional activity during brain development and how abnormalities in this process can lead to brain overgrowth and ASD.