By serving as the cofactor for the enzyme, activated factor Vll (FVIIa), tissue factor (TF) is critical for hemostasis. Preclinical and clinical data, however, have implicated TF in the progression and/or complications associated with a multitude of pathological conditions including atherothrombosis, ischemia/reperfusion injury, sepsis, acute lung injury/acute respiratory distress syndrome (ALI/ARDS), thrombotic microangiopathy (e.g. hemolytic uremic syndrome associated with E. coli verotoxin, certain drugs, and ricin toxicity), glomerulonephritis, antiphospholipid syndrome, inflammatory bowel disease, hepafic veno-occlusive disease (aka sinusoidal obstruction syndrome, associated with chemotherapy and following bone marrow transplantation), arthritis, organ transplant rejection, sickle cell anemia, cancer growth and metastasis, chemotherapy-associated thrombosis (e.g. thalidomide, lenalidomide) and post-surgical venous thromboembolic disease. Therefore the development of an agent(s) that could safely limit the action of TF would conceivably improve the medical therapy for many people.

Agency
National Institute of Health (NIH)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HL112303-03
Application #
8656779
Study Section
Special Emphasis Panel (ZHL1)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Zhou, Hui-fang; Yan, Huimin; Pan, Hua et al. (2014) Peptide-siRNA nanocomplexes targeting NF-?B subunit p65 suppress nascent experimental arthritis. J Clin Invest 124:4363-74
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Pozzi, Nicola; Chen, Zhiwei; Gohara, David W et al. (2013) Crystal structure of prothrombin reveals conformational flexibility and mechanism of activation. J Biol Chem 288:22734-44
Barranco-Medina, Sergio; Pozzi, Nicola; Vogt, Austin D et al. (2013) Histone H4 promotes prothrombin autoactivation. J Biol Chem 288:35749-57

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