- Yogen Kanthi, M.D. Research
As a cardiologist and clinical vascular medicine specialist, Dr. Kanthi’s laboratory aims to understand how inflammation and coagulation contribute to vascular disease. We are interested in developing a deeper understanding of how innate immune circuits and communicate with coagulation and the vessel wall to license or restrict thrombosis.
Dr. Kanthi joined the NIH to build a translational vascular medicine research program. His team has studied the role of inlammasome activation and purine signaling in venous thrombosis (JCI, ATVB, Nature Communications). The Laboratory of Vascular Thrombosis and Inflammation (LVTI)has made seminal discoveries in COVID-19 pathology, being the first to identify neutrophil extracellular traps in patients with COVID-19 (JCI Insight), a new calprotectin biomarker for COVID-19 severity (J Leuk Biol), and the discovery of prothrombotic autoAntibodies in patients with COVID-19 (Science Translational Medicine).
With expertise in thrombo-inflammation and vascular biology, Dr. Kanthi launched a clinical trial at the University of Michigan (NCT04399179) to test dipyridamole, a repurposed FDA-approved drug in patients with COVID-19.
The goal of the LVTI is to identify the molecular and cellular processes that lead to vascular thrombo-inflammation and design better therapeutic approaches for patients with vascular disease.
- Yogen Kanthi, M.D. Research
We are working closely with our collaborator, Dr. Jason Knight to leverage our strengths in inflammation and thrombosis, two processes at the heart of severe COVID-19 illness to understand this disease, and develop potential new treatments.
Our laboratory studies disease mechanisms in venous thrombosis with a major area of focus on regulation of venous homeostasis. We are exploring endogenous vasculo-protective enzymes that function at the intersection of inflammation and coagulation. We are also interested in disease pathways that are triggered by abnormal innate immune activation and cell stress responses that lead to an imbalance in coagulation and fibrinolysis. Our work utilizes human vascular cells and tissues from patients with vascular disease, primary cultures endothelial cells, and mouse models of venous thrombosis.
Veins are the most commonly used conduit to surgically bypass arterial stenoses. Veins are structurally distinct from arteries, and are forced to adapt to the arterial environment when used as arterial bypass grafts. Unfortunately, this remodeling can be pathologic and a high proportion of vein bypass grafts will fail, leading to ischemia or additional procedures. We are specifically studying the effect of extracellular nucleotide signalling in vein graft maladaptation. Using state-of-the-art mechanical stretch models that mimic vein graft function and mouse models of vein graft disease, our investigative efforts have focused on venous adaptations to arterial environments.