My research interests focus on the mechanisms whereby the transcription factors, Runx2 and Lef1, regulate gene expression in osteoblasts. Runx2 is required for bone formation and contributes to cancer-induced bone disease. We have identified multiple repression domains in Runx2 and are currently determining how these domains mediate interactions with other proteins to contribute to transcription repression. Among the proteins we have identified are four histone deacetylases (Hdacs) and a transcription factor (Lef1). Our studies focus on defining how the interactions of these proteins with Runx2 are regulated during osteoblast differentiation and cancer-induced bone disease. We utilize molecular biology, cell biology, biochemistry and mouse models to determine how Runx2, Lef1 and Hdacs regulate bone formation and bone disease associated with metastatic cancer.