We are interested in both cancer cell intrinsic and extrinsic programs that regulate primary tumor growth and initiation and progression of metastasis. Cancer cell intrinsic programs include aberrant signaling pathways mediated by loss of tumor suppressor genes and activation of oncogenes. Our approach is to investigate these pathways at several levels including transcriptional regulation, epigenetic regulation, and regulation by small regulatory RNAs. Cell extrinsic programs include the contribution of the tumor microenvironment. Here we are interested in dissecting the complexity of various cell types recruited from the bone marrow that& comprise the tumor microenvironment. We also study the cooperative heterotypic reciprocal signaling between the bone marrow progenitor cells and tumor epithelial compartments that influence tumor progression. Finally, we are interested in understanding how these two programs are integrated to regulate key tumorigenic processes including angiogenesis, inflammation, epithelial to mesenchymal transition, metastasis initiation and progression. A major aim is to rapidly validate insights obtained from these investigations in preclinical and clinical settings, and to determine the diagnostic and therapeutic potential of candidate molecules in collaboration with clinicians.