Description of Research Expertise

The main focus of my research has been on the link between inflammation and thrombosis, with an emphasis on the pathobiology of alpha-defensins, plasminogen activator system and recently developmental endothelial locus-1 (Del-1) and its role in chronic and acute thrombo-inflammatory diseases like thrombotic stroke, acute chest syndrome (ACS) in sickle cell disease. I was among the first to characterize a transgenic mouse that expresses human alpha-defensins in its neutrophils. It has been our underlying hypothesis that the lack of alpha-defensins in mouse neutrophils, the most abundant protein secreted by their activated human counterparts, together with the rapid apoptosis that these cells undergo in tissue, has led to an under-appreciation of their role in inflammatory and thrombotic disorders. I have extensive experience in the production, purification and characterization of human alpha defensins and Del-1 and diverse in vivo animal models of thrombosis, pulmonary embolism, acute lung injury, and ischemic stroke. My recent focus is the role of Del-1 as a pulmonary endothelial cell derived negative regulator of inflammation in the pathogenesis of ACS. My collaborators provided me with Del-1 knock out and over-expressors mice, and I have generated a novel CRISPR mouse with a single amino acid mutation essential for integrin binding and function of Del-1.