Research Abstract:
The goal of our research is an understanding of the initiation and control of hemostasis and the interrelationship between coagulation and inflammation. Rather than hemorrhagic phenomena, the investigative thrust concerns pathologic thrombosis and atherosclerosis.
Our investigations have recently centered on a novel endogenous coagulation inhibitor that circulates bound to plasma lipoproteins that we have isolated, cloned, expressed and characterized, called Tissue Factor Pathway Inhibitor (TFPI). TFPI is a multivalent Kunitz-type proteinase inhibitor that directly inactivates coagulation factor Xa and produces feedback inhibition of the factor VIIa/tissue factor catalytic complex, which is responsible for the initiation of coagulation. Additional work involves the characterization of a previously unrecognized regulator of coagulation we have termed the protein Z-dependent protease inhibitor. The aim of current studies is to define through both in vitro and in vivo experiments the role of coagulation in the inflammatory response and vascular diseases.
Work in the laboratory involves protein purification and characterization, kinetics of proteinase/inhibitor interactions, production of monoclonal and polyclonal antibodies for the development of immunoassays and histochemical studies, expression and characterization of native and mutant recombinant proteins for structure/function studies, and the assessment of particular interventions in animal models using transgenic and gene-deletion techniques.
Selected Publications:
Broze GJ Jr. Protein Z and protein Z-dependent protease inhibitor. In: RW Colman, J Hirsh, VJ Marder, AW Clowes, JN George editors. Hemostasis and Thrombosis, Fifth Edition, Lippincott Williams & Wilkins, Philadelphia, PA, 2006. p. 215-220.
Refaai MA, Ahn C, Lu L, Wu K, Broze GJ, Jr. Protein Z and ZPI levels and cardiovascular events. J Thromb Haemost 2006 4:1628-1629.
Al-Shanqeeti A, van Hycklama A, Berntorp E, Rosendaal FR, Broze GJ Jr. Protein Z and protein Z-dependent protease inhibitor: Determinants of levels and risk of venous thrombosis. Thromb Haemost 2005 93:411-413.
Ndonwi M, Broze GJ Jr, Bajaj SP. The first epidermal growth factor-like domains of factor Xa and fator IXa are important for the activation of the factor VII-tissue factor complex. J Thromb Haemost 2005 3:112-118.
Piro O, Broze GJ Jr. Comparison of cell surface TFPI? and TFPI?. J Thromb Haemost 2005 3:2677-2683.
Last Updated: 12/21/2006 |