Jason Knight is a rheumatologist whose research group studies the role of neutrophils in the thromboinflammatory complications of diseases such as antiphospholipid syndrome (APS), lupus, diabetes, and COVID-19. Clinically, Dr. Knight is an expert in the care of patients with APS, an autoimmune disease that is still primarily treated with anticoagulation, rather than immunomodulation. His group has contributed to shifting that paradigm, demonstrating that sticky, neutrophil-derived “spider webs” known as neutrophil extracellular traps (NETs) circulate at high levels in the blood of APS patients where they potentiate thrombin generation. Dr. Knight’s group has shown that NETs are required for APS-accelerated thrombosis in mice and that NET release by APS neutrophils can be restrained by direct and indirect adenosine receptor agonists such as regadenoson, dipyridamole, and defibrotide; his group is also interested in the extent to which natural compounds and dietary factors may modulate neutrophils and NET release. When the COVID-19 pandemic hit, Dr. Knight’s group recognized immunopathogenic similarities between APS and COVID-19 and pivoted their research efforts for most of 2020 to COVID-19. In April 2020, his group was the first to demonstrate the important role of NETs in COVID-19 pathogenesis, work that informed many clinical trials to evaluate NET-targeting therapies in COVID-19. Furthermore, after others reported in small case series that some patients with COVID-19 had positive testing for antiphospholipid antibodies, his group was the first to prove the prothrombotic potential of these autoantibodies by transferring COVID-19 antibodies into mice. Going forward, the goal of the Knight lab is to identify the subset of patients with thrombophilic diseases who can be treated not with lifelong anticoagulants, but rather agents that modulate the immune system.
Jason S. Knight, MD, PhD