My long-term interest is to understand how early neurodevelopment is shaped by genetics, physiology, and experience, and how they affect different brain regions and cell types to alter long-term brain function. I focus on developing chemical biology and genomic tools to study these question, spanning from invetebrate behavioral neuroscience to molecular biology in neocortical development.
As a Junior Fellow, I work with Aviv Regev, Feng Zhang and Paola Arlotta in developing a scalable genetic tool, in vivo Perturb-Seq, to study cell-intrinsic gene functions in developing tissues with single-cell resolution. We used in vivo Perturb-Seq to functionally evaluate 35 autism spectrum disorder/neurodevelopmental delay (ASD/ND) de novo loss-of-function risk genes. Using CRISPR-Cas9, we introduced frameshift mutations in these risk genes in pools, within the developing mouse brain in utero, followed by single-cell RNA sequencing of perturbed cells in the postnatal brain. We identified cell type-specific and evolutionarily conserved gene modules from both neuronal and glial cell classes. Recurrent gene modules and cell types are affected across this cohort of perturbations, representing key cellular effects across sets of ASD/ND risk genes. In vivo Perturb-Seq allows us to investigate how diverse mutations affect cell types and states in the developing organism.