Paul Salomon Mischel

I am a physician scientist trained in pathology and cancer biology. My lab has made a series of discoveries published in Nature, Science, and Nature Genetics, that have 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. I lead Team eDyNAmiC, which was awarded one of the $25M Cancer Grand Challenges Awards from CRUK and the National Cancer Institute, to tackle the extrachromosomal DNA grand challenge. My lab has also uncovered metabolic co-dependencies that are downstream consequences of oncogene amplification. These include a central role for altered biochemical mechanisms that regulate oncogene copy number and function. These discoveries have resulted in new understandings of some of the fundamental processes by which oncogene amplification drives cancer progression and drug resistance and pointed that way towards new treatments that are being developed.