New frontiers in functional genomics using high-throughput genome engineering
Forward genetic screens using CRISPR (clustered regularly interspaced short palindromic repeats)–associated nucleases like Cas9 are a powerful tool to pinpoint genes involved in disease. Initial screens capitalized on genome-scale libraries to perturb nearly all protein-coding genes in the human genome to examine therapeutic resistance and gene essentiality in cancer cell lines.
Recently, our lab has further developed the CRISPR screening toolbox in several new directions, including in vivo screens to understand drivers of lung metastasis, saturation mutagenesis of noncoding regions to identify functional elements that drive chemotherapeutic resistance in melanoma, and screens that dissect complex interactions between tumor cells and primary immune cells in cancer immunotherapy. Taken together, these new frontiers expand the potential of CRISPR screens for fundamental genomic discovery, gene regulation, and therapeutic development to overcome drug resistance.
Neville Sanjana is a Core Faculty Member at the New York Genome Center, and an Assistant Professor in the Department of Biology and Center for Genomics and Systems Biology at NYU. He is a recipient of the NIH Director’s New Innovator Award, the NIH Pathways to Independence Award, the Sidney Kimmel Scholar Award, and the Melanoma Research Alliance Young Investigator Award. His research includes pooled screening approaches for functional genomics and gene editing to create pluripotent stem cell and human neuron models of neurodevelopmental disorders.