Conventional chemotherapy fails to eradicate most human cancers including nearly all solid tumors, as well as many aggressive lymphomas and leukemias. Our research group seeks to identify new 'synthetic-lethal' strategies to target oncogene and microRNA signaling pathways and thus develop novel cancer therapies. Our work has sought to understand how specific oncogenes and miRNAs function to drive tumorigenesis. We are particularly focused on how cancer signaling pathways are activated in breast and liver cancers, amongst the most prevalent and deadly forms of human cancer. Using a variety of model systems we seek to develop anti-cancer therapeutics that target the basic cell cycle and may selectively inhibit cancer signaling pathways. For example, we have discovered that inhibition of cyclin-dependent kinase 1 (CDK1) causes growth arrest in most non-tumorigenic cells, however, cells transformed by the MYC oncogene are sensitized to undergo cell death. We have also discovered several oncogenic microRNAs which when inhibited can attenuate tumor formation in transgenic animal models. Our current studies seek to further define and validate cell cycle, microRNA and metabolic pathways which may serve as new 'synthetic-lethal' approaches to selectively kill tumor cells across a variety of cancer types. The long-term goals are to translate these findings into new treatments.