Adhesion to the extracellular matrix (ECM) or to neighboring cells regulates multiple cellular processes such as cell migration, morphogenesis, proliferation, gene expression and survival. Activation and regulation of these responses depends on multiple environmental cues, which are sensed and interpreted in specific cell-matrix and cell-cell adhesions. In our lab, we focus in particular on integrin- and cadherin-mediated adhesions, and study the mechanisms whereby they sense external surfaces, recognizing not only their chemical composition, but also their physical properties, including their topography, rigidity and ligand density. Systematic molecular modulation of the adhesion sites is used in an attempt to decipher the mechanisms whereby the adhesion-based molecular machinery integrates complex environmental information and triggers a coherent and robust response. Specifically, we combine a wide variety of molecular perturbation approaches with advanced, quantitative imaging technologies, to study cancer cell invasion and migration, osteoclast-mediated bone remodeling, platelet adhesion and activation, the formation and maintenance of the epithelial barrier function in the gut, the development of antigen-specific stimulatory surfaces that stimulate T-lymphocytes, and more.