In 1994 I moved to the University of Texas MD Anderson Cancer Center to join the faculty in the Department of Tumor Biology and continue my research on the retinoblastoma tumor suppressor gene. There I discovered that cyclin dependent kinases regulate the retinoblastoma tumor suppressor protein by site specific phosphorylation, providing scientific rationale for currently FDA approved therapies targeting cyclin dependent kinases. In 2001 I moved my laboratory to the Department of Pharmacology & Therapeutics at Roswell Park Comprehensive Cancer Center. In recent years my lab has focused its attention on non-canonical functions of tumor suppressor genes, including how genetic alterations in these genes drive cancer lineage plasticity, metastasis, and therapeutic resistance. We are using this information to identify new ways to improve therapeutic outcomes by suppressing cancer lineage plasticity.