Yun Li will investigate the effects of candidate ASD genes on neural and glial development and on cell-cell communication using human stem cell-derived 2-D neural cultures and 3-D brain organoids.

Genetic studies of ASD implicate alterations in synaptic development and signaling, with the synaptic protein neurexin-1 playing a pivotal role. Ann Marie Craig aims to develop new approaches to overcome neurexin-1-linked synaptic deficits in ASD by modulating the remaining NRXN1 allele to boost neurexin-1 function and restore synaptic structure and function.

Len Pennacchio will utilize his laboratory’s expertise in high-throughput enhancer screening to experimentally test whether noncoding autism-associated sequence variants alter the function of transcriptional enhancers that normally drive gene expression in the developing brain.

Jonathan Mill’s project aims to characterize multiple layers of gene regulation during brain development, facilitating a systematic exploration of hypotheses related to the neurodevelopmental origins of autism. Further, by characterizing genetic effects on gene regulation during neurodevelopment, this work will facilitate the interpretation of genetic findings for autism.

Early ASD diagnosis is crucial for the initiation of behavioral therapies — therapies which often lead to a better outcome for affected individuals. Veerle Somers will identify and characterize novel maternal autoantibodies associated with the development of ASD in offspring. These findings have the potential to uncover predictive and diagnostic biomarkers for ASD and could elucidate novel etiological mechanisms of early impairment of fetal brain development in ASD.

Gordon Fishell and Jordane Dimidschstein will combine human genetic data with large-scale transcriptomic and epigenetic analyses to assess how alterations in autism risk genes affect biological processes occurring within GABAergic and cholinergic neuronal populations during the early stages of fate specification.

Seth Shipman will apply newly developed technology, called ‘molecular recordings,’ to determine the precise timing of transcriptional events that occurs within individual cell types in the developing brain, in order to provide a more robust framework to guide investigations into how ASD-linked mutations alter brain development.