The IPP complex The integrin-linked kinase, pinch, parvin (IPP) complex is ia hub in integrin-actin and integrin-signaling networks, and in mammalian systems complex formation precedes and is required for its correct targeting to adhesions. In addition, IPP complex formation protects its components from proteasomal degradation. The IPP complex has critical roles in anchorage-dependent cell growth and survival, cell cycle progression, epithelial to mesenchymal transition, cell motility, contractility and early development. The complex is also required for cardiac, vascular, brain, kidney, muscle, skin, platelet, chondrocyte and T cell function and plays important roles in tumor angiogenesis. We are interested in understanding the structural basis for IPP complex formation and the mechansisms of function. The CCM complex Cerebral cavernous malformation (CCM) has a prevalence of 0.1-0.5% in the human population and is an important cause of hemorrhagic stroke. Between 10 and 50% of CCM cases are associated with inherited autosomal-dominant mutations in three genes, CCM1, CCM2 and CCM3. These mutations are associated with destabilized vascular endothelial cell-cell interactions and CCM lesions. The molecular mechanisms for acquisition of CCM lesions are only beginning to be described, and the atomic-level interactions that become disrupted in CCM and their functional consequences have not yet been investigated. We are studying CCM3, CCM2 and CCM1 using a structure-directed functional approach. Our laboratory collaborates with the Calderwood and Min laboratories on cytoskeletal protein complexes.