Vascular Immunobiology Mechanistic and Translational Studies

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

Our discovery of neutrophil hyperactivation, neutrophil extracellular trap formation, the production of pathologic prothrombotic autoantibodies that perturb endothelial and innate immune function in acute critical illnesses have led us to examine additional clinical contexts where autoantibodies and thromboinflammation may be clinically relevant. 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 diseases at large, we are dissecting cellular phenotypes and molecular signaling networks using human samples from multiple, NIH- and non-NIH sponsored clinical studies across a spectrum of diseases, including from randomized clinical trials. These studies include mentoring of early career faculty. We are correlating findings with clinical outcomes to lend context to the trial results, and these analyses are important to lay the groundwork for mechanistic insights that segue into diagnostic and therapeutic targets in future clinical studies.