Dialogue between genomic instability and metabolism in diseases

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

The DNA damage response (DDR) is a signaling network that enables cells to detect and repair genomic damage. Over the past three decades, inhibiting the DDR has proven to be an effective cancer therapeutic strategy. Although cancer drugs targeting the DDR have received approval for treating various cancers, tumor cells often develop resistance to these therapies, in large part due to their ability to undergo energetic metabolic reprogramming. Metabolic intermediates influence the ability of tumor cells to sense oxidative stress, leading to impaired redox metabolism that creates redox vulnerabilities. The overarching goal of my group is to elucidate the complex interplay between the DDR and redox metabolism. To this end, we employ CRISPR-based high-throughput screens, mouse models of cancer, and other molecular biology tools, to investigate combination therapies that target the DDR, and redox metabolism in tumor cells.