Interpreting the Impact of ASD Gene Mutations Using Pluripotent Stem Cells

The autism genome is comprised of genes that directly regulate protein expression and genes that indirectly regulate activity by turning on or off genes that affect protein expression. The latter genes are described as  “epigenetic” and are influenced by both genetic mutations and environmental factors. What is not known is whether epigenetic mutations affect downstream processes related to autism like altering connections or function of brain cells. This project will use human induced pluripotent stem cells, or iPSCs, with a mutation of a gene called SETD1A that controls epigenetic gene regulation to examine the effects of mutations on gene expression in different types of cells. In addition, this fellow will examine how these mutations affect brain cell shape and functionality. Finally, they will investigate whether these effects are reversible, leading the way to new therapies that can help those with ASD.