Brown University School of Engineering

Biomedical Engineering Seminar: Prof. Craig Lefort (Rhode Island Hospital)

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Thursday, March 06, 2014 2:00pm - 3:00pm

"Inside-out" activation of leukocyte integrins Craig Lefort, Ph.D. Assistant Professor of Surgery (Research) Rhode Island Hospital, Alpert Medical School of Brown University Abstract: Integrins are adhesion and signaling receptors that play critical roles in leukocyte trafficking during the immune response. The integrin LFA-1 plays a dominant role in the adhesion of neutrophils (the first responding leukocytes) to inflamed endothelium by binding to its ligand ICAM-1. The affinity of integrin for ligand is determined by its global structure, regulated by the binding of proteins to the integrin cytoplasmic tails in a process called "inside-out" activation. At least three different integrin affinities have been observed and these are characterized by distinct conformations. Neutrophils employ these different LFA-1 activation states to perform distinct biophysical behaviors. I will describe our work which takes advantage of differential neutrophil behavior to probe the mechanisms that determine the conformational state of LFA-1.