Our laboratory’s main focus is modeling the complexities of Alzheimer’s disease (AD) by using CRISPR-mediated genome-editing to introduce specific causal and risk mutations into human pluripotent stem cells (hPSCs), thus allowing more robust cross comparisons between genotypes and the creation of allelic libraries in similar genetic backgrounds. We then differentiate hPSCs into a variety of human central nervous system (CNS) cell types for functional assays, multi-omic analysis, and therapeutic screening. We also manipulate risk and protective genetic variants via CRISPRi and more traditional methods like siRNA and lentiviral overexpression. In addition to disease modeling, we also focus on improving stem cell technology by developing novel or refined methods of hPSC differentiation into CNS cell types in monolayer or 3D conditions. Our approach is very collaborative and we work with many groups within the Taub Institute.