This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) will support research at the University of California, Los Angeles (UCLA) to investigate the structure and specificity of the TFPI-2 protein and its potential as a therapeutic agent to inhibit fibrinolysis.
The $511,135 award, effective September 9, 2024 through August 31, 2025, will fund efforts to delineate the specific residues and mechanisms by which the TFPI-2 Kunitz domain 1 (KD1) inhibits proteases like plasmin, factor XIa, and plasma kallikrein. Additionally, the project will assess the efficacy and safety of two TFPI-2 KD1 variants as potent and selective inhibitors of plasmin in mouse bleeding models, and evaluate the most promising variant in a rat trauma model. The goal is to develop a therapeutic agent that can effectively inhibit fibrinolysis to reduce bleeding complications in surgeries and trauma without the adverse effects of broad-spectrum protease inhibitors. The research aims to advance the fundamental understanding of coagulation and fibrinolysis mechanisms while ultimately producing a targeted therapeutic option.
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