Unraveling Cytotoxic and Thrombotic Signals in Host-defense Responses

National Heart, Lung, And Blood Institute

Investigators

Linked publications & trials

Abstract

Infections that trigger a hyperinflammatory host-defense response place individuals at high risk for thrombosis and tissue malperfusion. The resulting organ failure can result in the mortality and morbidity associated with critical illness. In pursuit of novel and improve therapeutic approaches to combat infection-associated thrombosis and vascular dysfunction, we undertook mechanistic, translational studies using patient samples, in vitro studies, and animal modeling that identified several mechanisms of thrombosis and potential therapeutic targets. These studies resulted in new insights about thromboinflammation including neutrophil extracellular traps, neutrophil activation biomarkers, prothrombotic autoantibodies, shifts in the immune landscape, and endothelial dysfunction that converged into clinical trials advanced in the extramural NIH and at the Clinical Center. These studies included direct and indirect mentoring of two early career faculty. These published and further ongoing studies related to autoantibodies and immune landscapes have been pivotal in advancing the HHS/NIH mission to respond to current and future threats to public health.