Research Interests
The Mackman lab studies the role of tissue factor (TF), coagulation proteases, protease activated receptors (PARs) and extracellular vesicles (EVs) in mouse models of hemostasis, thrombosis, endotoxemia, ischemia-reperfusion injury, cancer, obesity, atherosclerosis and viral infection. My lab has generated and obtained several unique mouse lines that have altered levels of TF, PAR1, and PAR2 for these studies. We have been studying mechanisms of cancer-associated thrombosis since 2007. We have shown that elevated levels of EV TF activity are associated with venous thromboembolism (VTE) in pancreatic cancer patients but not other types of cancer. We have also demonstrated a role for tumor-derived TF+ EVs and neutrophils and neutrophil extracellular traps (NETs) in venous thrombosis in mice bearing human pancreatic tumors. My lab also started studying the role of the clotting cascade in viral infection in 2007. We established both the Coxsachievirus B3 (CVB3) model, which causes myocarditis, and influenza A (H1N1) mouse model. We found that the TF-thrombin-PAR1 pathway enhances the TLR3-dependent antiviral response in mice infection with CVB3. In the H1N1 model PAR1 protects mice by suppressing excess neutrophil recruitment into the lung.
