The Gupta Lab studies the gene regulatory networks that cause vascular disease using high-throughput CRISPR screens. We have expanded Perturb-seq methods to cover all 20,000 genes and identified co-regulated gene networks using AI/ML methods. For coronary artery disease we identified a novel collection of variants that regulate endothelial cell shear stress response (Schnitzler, et al. Nature 2024). Surprisingly the genes in this pathway are also associated with increased risk of a rare neurovascular disease-Cerebral Cavernous Malformations. We are studying how these variants affect cellular function in different cell types and stages of development. Additionally, we are using new types of genome-wide CRISPR screens to discover the risk pathways for multiple cardiometabolic traits in other vascular cells, immune cells, and hepatocytes.
