In the vast majority of solid tumors, genomic instability manifests itself as gross structural and numerical abnormalities affecting chromosomes. This phenotype, termed chromosomal instability (CIN), accounts for the aneuploidy and chromosomal rearrangements found in virtually all cancer cells at the cytogenetic level. Our lab is broadly interested in the mechanisms that control the fidelity of chromosome transmission in human cells, which we suspect may be disrupted in some CIN cancers. To do this, we exploit novel methods that we recently developed to delete genes in cultured human cells. We can thus rapidly generate isogenic cell lines in which a particular gene has been ‘knocked out,’ either constitutively or conditionally.