The Leukocyte Biology Laboratory is interested in understanding the molecular mechanisms of phagocyte activation. Specifically, we are studying the role of cytoskeletal proteins such as the leukocyte specific actin bundling protein L-plastin (LPL), in regulating the signaling cascades which lead to the development of the effector phenotype in neutrophils and macrophages.
We are defining the role of LPL and the actin cytoskeleton in regulating signal transduction pathways during integrin activation and the role of beta 2 integrin (CD11/CD18 complex) activation in adhesion, respiratory burst and reactive oxygen production, degranulation, prostaglandin and leukotriene production, migration, and phagocytosis. We are applying this information to clinically important inflammatory diseases, particularly gastrointestinal inflammation and arthritis. For example, we are studying the role of neutrophils in mucosal injury during gastrointestinal inflammation induced by ischemic injury and the mechanism of neutrophil and macrophage activation in immune complex disease such as rheumatoid arthritis. We are also interested in the strategies used by intracellular bacterial gastrointestinal pathogens such as Salmonella, to invade macrophages, modulate their activation, induce apoptosis, and subsequently evade the host immune response.