Every living cell in our body is composed of hundreds of thousands of proteins. These proteins are highly coordinated in their functions and are fundamental to our life. The broad theme of our research is to understand the molecular basis of some key protein-protein interactions in cell signaling and their dysfunctions in human diseases. We are currently focusing on a class of cell surface receptors, integrins, and their associated proteins. Integrins are major components of cell-extracellular matrix (ECM) adhesion, cell morphology, and cell motility. Using structural biology techniques, including NMR spectroscopy and crystallography, we are building a molecular landscape of integrin-mediated protein interaction network. Our work has significantly advanced the field by providing atomic-level visualization of some important part of this network and mechanistic insight of integrin signaling. In collaboration with a group of cell biologists and clinical scientists, we were able to link our recent atomic findings in integrin network to the pathogenesis of several human disorders such as thrombosis and cardiac failure. We will continue to resolve the molecular puzzle of this network to gain fundamental understanding of the integrin-mediated cell adhesion events. Our studies may ultimately lead to better approaches for investigating and treating the relevant human diseases.