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The Mischel laboratory has identified a central role for ecDNA (extrachromosomal DNA) in cancer development, progression, accelerated tumor evolution and drug resistance. These findings have provided a new understanding of the fundamental mechanisms of oncogene amplification and the spatial organization of altered tumor genomes, launching a new area of cancer research that links circular architecture with tumor pathogenesis.

Working closely with our collaborators in Team eDyNAmiC, we aim to bring new perspectives, new technologies, and new ways to diagnose and treat patients with some of the most aggressive forms of cancer by attacking the unstable genome and drugging the as-yet undruggable. We aim to identify and target the underlying mechanisms that generate ecDNA formation, transcription, and immune evasion as a class. By working with such an outstanding set of colleagues through Team eDyNAmiC, we have the unique opportunity to integrate cell biologic and live-cell imaging to monitor ecDNA in live cells, CRISPR-based and functional technologies to perturb and modulate ecDNAs, evolutionary theory, machine learning and mathematical approaches, and direct learning from patients to better understand the role of ecDNA in human cancer and to identify actionable vulnerabilities.