The Mackman lab studies the roles of tissue factor (TF), coagulation proteases and protease-activated receptors (PARs) in health and disease (Figure 1). We have established a variety of different disease models and have a larger number of transgenic mice deficient in different coagulation factors and PARs, as well as mice with low levels of TF and mice with cell type-specific knockout of TF, PAR1 and PAR2. We also use antibodies and pharmacological inhibitors of FXa and thrombin (Figure 1).
The TF:FVIIa complex is the physiological initiator of the blood coagulation cascade (Figure 2). Several anticoagulant pathways, such as tissue factor pathway inhibitor (TFPI), regulate the coagulation cascade. A balance between TF and TFPI is require for normal hemostasis. The fibrinolytic pathway regulates the generation of plasmin, which degrades the clot (Figure 2).