Maria Chahrour plans to assess, in both human tissue and mouse models, whether derepression of L1Hs retrotransposon activity plays a role in the pathobiology of ASD. This initiative will establish a new potential etiology for ASD, supporting fresh opportunities for diagnosis and treatment.

Pierre Mattar proposes to identify and characterize how chromatin-remodeling enzymes regulate neurogenesis in the developing brain and how dysfunction in these complexes contribute to ASD. Specifically, his team aims to determine how chromatin-remodeling functions are disrupted by ASD-linked mutations in ADNP, a gene that encodes a transcription factor that interacts with chromodomain helicase proteins, and how this affects neural progenitor cell function in the developing mouse neocortex.

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.