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)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HL112303-03
Application #
8656779
Study Section
Special Emphasis Panel (ZHL1)
Project Start
Project End
Budget Start
2014-05-01
Budget End
2015-04-30
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
Barranco-Medina, Sergio; Murphy, Mary; Pelc, Leslie et al. (2017) Rational Design of Protein C Activators. Sci Rep 7:44596
Shen, Guomin; Cui, Weidong; Zhang, Hao et al. (2017) Warfarin traps human vitamin K epoxide reductase in an intermediate state during electron transfer. Nat Struct Mol Biol 24:69-76
Chakraborty, Pradipta; Di Cera, Enrico (2017) Induced Fit Is a Special Case of Conformational Selection. Biochemistry 56:2853-2859
Sadler, J Evan (2017) Pathophysiology of thrombotic thrombocytopenic purpura. Blood 130:1181-1188
Liszewski, M Kathryn; Java, Anuja; Schramm, Elizabeth C et al. (2017) Complement Dysregulation and Disease: Insights from Contemporary Genetics. Annu Rev Pathol 12:25-52
Vedantham, Suresh; Goldhaber, Samuel Z; Julian, Jim A et al. (2017) Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med 377:2240-2252
Lokki, A Inkeri; Daly, Emma; Triebwasser, Michael et al. (2017) Protective Low-Frequency Variants for Preeclampsia in the Fms Related Tyrosine Kinase 1 Gene in the Finnish Population. Hypertension 70:365-371
Sanfilippo, K M; Wang, T F; Gage, B F et al. (2016) Incidence of venous thromboembolism in patients with non-Hodgkin lymphoma. Thromb Res 143:86-90
Wagner, Erin K; Raychaudhuri, Soumya; Villalonga, Mercedes B et al. (2016) Mapping rare, deleterious mutations in Factor H: Association with early onset, drusen burden, and lower antigenic levels in familial AMD. Sci Rep 6:31531
Gillrie, Mark R; Renaux, Bernard; Russell-Goldman, Eleanor et al. (2016) Thrombin Cleavage of Plasmodium falciparum Erythrocyte Membrane Protein 1 Inhibits Cytoadherence. MBio 7:

Showing the most recent 10 out of 81 publications