Arnold Kriegstein will apply single-cell RNA sequencing technologies to brain tissue samples from individuals with Dup15q syndrome, a genetically defined type of ASD, as well as to cerebral organoids derived from Dup15q-induced pluripotent stem cells. The goal of the project is to identify which cell types are affected by ASD during development and how this impacts mature brain circuits.

Jun Huh will examine human-derived bacteria that can colonize the guts of pregnant mice to identify bacteria that can promote anti-inflammatory responses. Such factors could help to prevent the development of brain pathologies and behavioral phenotypes relevant to autism in offspring that can be triggered by uncontrolled inflammatory activity during pregnancy.

Nael Nadif Kasri will assess differences in neuronal network activity and transcriptional profiles in neural cells derived from induced pluripotent stem cells from individuals with syndromic forms of ASD, building a phenotypic map based on network activity and cellular profiles. These phenotypic maps will aid in the dissection of the underlying cellular and molecular mechanisms involved in distinct forms of ASD.

Genomic and transcriptomic studies implicate fetal cerebral cortex transcriptional dysregulation in ASD, but the implicated regulatory elements, their target genes and their role in development remain unclear. Flora Vaccarino will use cortical organoids derived from individuals with ASD to investigate whether transcriptional dysregulation of specific cell types during early development represents a convergent pathophysiology in ASD.