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For neutrophils to perform their function as the primary cellular component of the innate immune response they must undergo a series of phenotypic changes, converting them from benign cells, capable of circulating without inducing tissue injury, to cells capable of migration into tissue and release of toxic agents capable of killing bacteria or injuring normal cells.

My laboratory is interested in understanding the molecular mechanisms leading to the activation of neutrophils and their participation in inflammatory diseases. We have determined that p38 MAPK is crucial to respiratory burst activity, exocytosis, and priming of neutrophil activation by cytokines.

In collaboration with Drs. Ward and Uriarte, current projects are:

• examining the control of granule exocytosis by various kinases and the participation of exocytosis in neutrophil functional responses
• applying state-of-the-art proteomics to identify the constituents of the various granule subsets and to identify the targets of Src tyrosine kinases and p38 MAPK that mediate exocytosis
• examining the role of granule exocytosis in neutrophil-mediated tissue injury, bacterial killing, chemotaxis, phagocytosis, and respiratory burst activity.
• using peptide inhibitors of exocytosis to define the contribution of granule release to neutrophil functions in vitro and in vivo.

The knowledge generated from these projects will be used to provide new approaches for therapeutic manipulation of neutrophil participation in post-traumatic central nervous system injury, ischemia-reperfusion injury, immune complex diseases, vasculitis, and sepsis.

Graduate Students:

Gregory Luerman, Department of Biochemistry and Molecular Biology

Research Technicians:

Suzanne Eades
Terri Manning