The primary focus of Dr. Lefort's lab is on elucidating the mechanisms of leukocyte integrin activation. Integrins are adhesion receptors that are critical for leukocyte trafficking by allowing them to interact tightly with the blood vessel wall. The affinity of integrins is highly regulated by proteins that bind to their short cytoplasmic tails and change the structure of the integrin extracellular domains -- a process called "inside-out" activation. We discovered that two of these proteins, Talin-1 and Kindlin-3, play distinct roles in regulating beta-2 integrin activation. We are now further dissecting the molecular details of integrin activation and investigating how the roles of integrins (and their activation) varies across leukocyte subsets and in different vascular beds throughout the body.