What are the mechanisms that regulate the migration of leukocytes into areas of inflammation? How do tumor cells invade and metastasize? Cell migration plays a central role in many different disease processes including cancer, heart disease, asthma and arthritis. Insight into the mechanisms that regulate cell migration will contribute to our understanding of basic cellular processes, but will also lead to the development of new therapeutic approaches for a wide variety of medical conditions.
Despite extensive interest in the receptors and mechanisms involved during cell migration, many fundamental questions remain unanswered. What are the mechanisms by which a cell initiates and then subsequently stops directional cell migration? How are adhesive events coordinated both temporally and spatially to promote productive, directional cell movements? Our research is aimed at understanding the cellular and molecular mechanisms that regulate cell migration and how defects in cell migration contribute to human disease. We use both in vitro approaches and in vivo model systems including mice and the genetic model system zebrafish.
Cell surface adhesion receptors, including integrins and cadherins, play a central role in during cell migration. Our previous studies have demonstrated that cell migration speed and cell invasiveness are modulated by integrin-ligand binding affinity and cytoskeletal linkages. We have recently identified the calcium-dependent protease calpain as a regulator of integrin-cytoskeletal interactions during cell migration. Specifically we find that calpain modulates integrin-cytoskeletal interactions and cell detachment.