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UNC Blood Research Center

Overview

Overview

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 large 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.

 

Cancer and viral infections affect tissue factor, coagulation proteases, and PARS function and levels, which in turn affect thrombosis and immune response.

 

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.

 

Schematic of the coagulation cascade, with inhibitors. Description of important features in previous text.