Regulation of the mammalian cell division cycle is critical to development and disease.  Loss of proliferative control during development is catastrophic, as it can lead to genome instability, apoptosis, and tissue degeneration.  Loss of cell cycle control is also important in disease pathology, as deregulated proliferation is a defining feature of cancer.  A key regulator of progression through the G1 phase of the cell cycle is the pathway controlled by the Retinoblastoma protein (pRB).  It functions beyond G1-S control and has implications for cancer pathogenesis, treatment choice, and outcome.  We are investigating this multifaceted pathway.