Our laboratory studies the response to genomic DNA damage in mammalian cells. Double stranded breaks (DSBs) are among the most dangerous DNA lesions as they can be resolved aberrantly forming chromosomal translocations and deletions that can lead to cellular transformation and cancer. We haveelucidated novel pathways activated by DNA DSBs generated during antigen receptor gene assembly in developing lymphocytes. How these pathways function to maintain genome stability, regulate normal lymphocyte development and impact the function of mature adaptive and innate immune cells is a current focus of the lab. More recently we have also beenstudying features of DNA DSB repair that are unique to cancer cells and are potential targets for novel cancer therapeutics. To this end we have developed cancer cell lines where we can induce DNA DSBs at defined genomic locations and mouse models of genome instability and cancer. CRISPR/Cas9 screens are being used to identify novel components of these pathways that could be targets for new classes of cancer therapeutics.