Sepsis is caused by microorganism-disseminated infection, with Gram-negative bacteria accounting for ~60% of all cases. Treatment for this condition includes administration of antibiotics and fluids, and costs 20 billion dollars per year. To date, all immunomodulatory therapies developed to treat sepsis have failed during clinical trials, highlighting an urgent need to unravel the pathophysiology of this syndrome, with the goal of developing new, effective drugs. Sepsis is characterized by a host response that includes release of cytokines by innate immune cells to combat the infection and is often associated with thrombosis. Disseminated intravascular coagulation is a hallmark of severe sepsis and is a major cause of mortality. A better understanding of the cellular and molecular pathways that lead to disseminated intravascular coagulation in sepsis is imperative for designing new therapeutic interventions. Neutrophil extracellular traps (NETs) are major drivers of disseminated coagulation in sepsis and their formation is tightly regulated by extrinsic and intrinsic programs. Recent studies underscore that interactions between platelets and neutrophils are critical for driving the formation of NETs and in sustaining Disseminated intravascular coagulation.
We are currently studying the intracellular pathways in both neutrophils and platelets that facilitate disseminated intravascular coagulation in order to identify new therapeutic targets.