Genome instability is a hallmark of cancer. Our lab combines sensitive, high-throughput, genomic assays, and computational modeling, in order to crack the genomic code that drives genome instability in different cell-types, pathologies and conditions, and to grasp the landscape of DNA lesions in cancer. We are particularly interested in the “double-edged swords” of the genome – physiological mechanisms that impose a threat on genome integrity, such as those involve in the formation of the immune repertoire, or the relief of DNA torsional stress. We investigate how these processes are targeted across the genome, how they are controlled, and what makes certain genomic sites more vulnerable than others to the “off-target” activity of these processes. Understanding this natural fragility of the genome will enable us to predict oncogenic events and to mark targets for cancer diagnosis and therapy.