Vascular Immunobiology Mechanistic and Translational Studies

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Our nascent discovery of neutrophil hyperactivation, neutrophil extracellular trap formation, the production of pathologic prothrombotic autoantibodies that perturb endothelial and innate immune function in acute COVID have led us to examine additional clinical contexts where autoantibodies and thromboinflammation could have clinical relevance. We identified an FDA-approved drug that modulates the immune and coagulation systems through purinergic signaling, and moved this to the clinic in an investigator-initiated, randomized clinical trial. To elucidate mechanisms and potential therapeutic targets in thromboinflammatory disease, we are dissecting cellular phenotypes and molecular signaling networks using samples from patients enrolled in three, NIH-sponsored, randomized, COVID clinical trials. We are correlating findings with clinical outcomes to lend context to the trial results, and these analyses are important to lay the groundwork for diagnostic and therapeutic targets in future clinical studies.