Wednesday, November 9, 2022

CCMB Seminar: Jesse Engreitz, Ph.D.

4:00 PM to 5:00 PM

Palmer Commons, Forum Hall

"From variants to functions for coronary artery disease: Systematic Perturb-seq links GWAS loci to disease programs in endothelial cells"


Genome-wide association studies (GWAS) have discovered >200 associations for coronary artery disease (CAD), each of which could point to genes and pathways that influence disease risk. It is thought that a fraction of these CAD risk loci influences the functions of endothelial cells, and that genes in multiple GWAS loci might act together in certain pathways. Yet, identifying these genes and pathways has proven challenging: each GWAS locus can have 2-20 candidate genes, a gene may participate in one or more pathways in a given cell type, and it remains unclear which genes and pathways would be likely to influence disease risk. I will present our work to address this challenge by developing a Variant-to-Gene-to-Program (V2G2P) framework to study the role of endothelial cells in coronary artery disease, involving building a Variant-to-Gene map with ABC and a Gene-to-Program map with systematic Perturb-seq. Our study nominates new genes that likely influence risk for CAD, identifies convergence of CAD risk loci into certain gene programs in endothelial cells, and demonstrates a generalizable strategy to catalog gene programs to connect disease variants to functions.

Jesse Engreitz

Jesse Engreitz, Ph.D.

Assistant Professor of Genetics, Stanford Medicine

Jesse is currently an Assistant Professor at Stanford University in the Department of Genetics and the Children’s Heart Center Basic Sciences and Engineering (BASE) Initiative, and is a recipient of the NHGRI Genomic Innovator Award. He co-leads a Functional Characterization Center at Stanford for the Impact of Genomic Variation on Function (IGVF) Consortium, and is an Associate Director of the Novo Nordisk Foundation Center for Genomic Mechanisms of Disease at the Broad Institute.

Previously, Jesse was a Junior Fellow at the Harvard Society of Fellows and led a research group at the Broad Institute of MIT and Harvard. During his postdoctoral fellowship at the Broad Institute, Jesse developed large-scale CRISPR tools to map enhancer-gene regulation with Eric Lander and Nir Hacohen, and launched the Variants-to-Function (V2F) Initiative to connect genetic disease variants to their molecular and cellular functions. Jesse previously attended Stanford University, where he developed computational algorithms for analyzing gene expression with Russ Altman, and completed his PhD in the Harvard-MIT Division of Health Sciences and Technology, where he studied genome regulation by long noncoding RNAs with Eric Lander and Mitch Guttman. His research has been supported by the National Human Genome Research Institute, National Heart, Lung, and Blood Institute, Additional Ventures, Foundations for the National Institutes of Health, Harvard Society of Fellows, Fannie and John Hertz Foundation, and Department of Defense. Outside the lab, Jesse enjoys playing jazz/rock/funk, testing Chinese recipes, and surfing.