I am interested in a number of areas relevant to cancer biology. I have had extensive experience in unraveling the signaling pathways involved in sensing and responding to DNA damage. This has involved both yeast and mammalian systems. I am continuing to explore new avenues in DNA damage signaling. In additon to our interests in DNA damage and cell cycle regulation in general, I have worked extensively in the past on Cdk regulation including Cdk2, cyclin A, cyclin F, and the p21 family of Cdk inhibitors, CKIs, including the Beckwith-Weidemann gene, p57. More recently our studies of cyclin and CKI metabolism led to the discovery of F-box proteins and the SCF pathway of regulated protein stability. The SCF pathway has been shown to be of broad significance in biology. More recently, he and his collaborators have developed technology to perform genetic screens in mammalian tissue culture cells to explore cell cycle and growth regulatory pathways as well as viral replication. These studies led to an appreciation of the extensive role of halploinsufficiency in driving tumorigenesis and provide evidence for a novel theory that explains how aneuploidy drives tumorigenesis.