Human Translational Studies of Vascular Thrombosis and Inflammation

National Heart, Lung, And Blood Institute

Investigators

Linked publications & trials

Abstract

Thrombosis presenting as venous thromboembolism, stroke, and heart attack is the leading cause of death in the United States. Many of these patients develop thrombosis despite use of antithrombotic drugs, highlighting a need for scientific and therapeutic advancements to reduce cardiovascular mortality and morbidity. Recent discoveries by several groups including ours about the intersection points of inflammation and coagulation have led to a resurgence of interest in the inflammatory mechanisms underpinning thrombosis and vascular disease. In pursuit of a deeper understanding of disease mechanisms and therapeutic opportunities, we utilize clinical and translational tools to characterize the clinical phenotype, and cellular and molecular processes of vascular thromboinflammation. Using multiple, complementary approaches that combine human, murine, and preclinical in vitro/ex vivo studies, we examine vascular disease in a bedside-to-bench and bench-to-bedside approach. These are centered around the following projects: Project (1): Purinergic Dysregulation. Patients with inherited or acquired dysfunction in purinergic signaling are at risk of developing vascular complications. Our studies use patient samples and clinical correlation to probe mechanistic pathways related to inflammatory and thrombotic signaling. Investigations also probe the processes that lead to unrestrained inflammation in patients with human coronavirus. The results of these studies will have implications for multiple patient populations including patients with monogenic disorders, and patients with treated with checkpoint inhibitors for cancer which may release the endogenous brakes on thromboinflammation. Project (2): Autoinflammation. We previously discovered the role of inflammasome activation and interleukin-1beta in venous thrombosis. Our current studies aim to further elucidate the hematologic and vascular processes in patients with acquired and inherited autoinflammatory disorders. These investigations are highly likely to lead to meaningful advances in science and public health.