Abstract

This project melds the efforts of five interacting research groups. Its general goal is better understanding of the roles of the blood clotting factors, particularly Fs. VIII and IX, in hemostasis and thrombosis. The strategy is to utilize biochemical and biophysical methods to examine the structure and function of Fs. VIII and IX; to examine their antigenic determinants using both hetero- and allo-polyclonal-antibodies, and monoclonal antibodies raised against entire factors as well as various fragments; to study the assembly of F. VIII in endothelial cells utilizing the methods of somatic cell genetics; and to clone the gene for canine F. IX utilizing the methods of molecular biology. These research programs are closely related to the large in-patient and out-patient services of the NC Memorial Hospital which are concerned with treating patients having disorders of hemostasis and thrombosis. An intimate relation exists between these clincal services and the research programs of the proposed project, and there will be collaborative research involving the basic scientists and clinicians.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL006350-24
Application #
3097393
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1979-01-01
Project End
1988-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
24
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Boulaftali, Yacine; Owens 3rd, A Phillip; Beale, Ashley et al. (2016) CalDAG-GEFI Deficiency Reduces Atherosclerotic Lesion Development in Mice. Arterioscler Thromb Vasc Biol 36:792-9
Bode, Michael F; Mackman, Nigel (2016) A combined deficiency of tissue factor and PAR-4 is associated with fatal pulmonary hemorrhage in mice. Thromb Res 146:46-50
Owens 3rd, A Phillip; Edwards, Todd L; Antoniak, Silvio et al. (2015) Platelet Inhibitors Reduce Rupture in a Mouse Model of Established Abdominal Aortic Aneurysm. Arterioscler Thromb Vasc Biol 35:2032-2041
Wu, Sangwook; Lee, Chang Jun; Pedersen, Lee G (2014) Analysis on long-range residue-residue communication using molecular dynamics. Proteins 82:2896-2901
Bode, Michael; Mackman, Nigel (2014) Regulation of tissue factor gene expression in monocytes and endothelial cells: Thromboxane A2 as a new player. Vascul Pharmacol 62:57-62
Wu, Sangwook; Beard, William A; Pedersen, Lee G et al. (2014) Structural comparison of DNA polymerase architecture suggests a nucleotide gateway to the polymerase active site. Chem Rev 114:2759-74
Perera, Lalith; Beard, William A; Pedersen, Lee G et al. (2014) Applications of quantum mechanical/molecular mechanical methods to the chemical insertion step of DNA and RNA polymerization. Adv Protein Chem Struct Biol 97:83-113
Parker, Christine H; Morgan, Christopher R; Rand, Kasper D et al. (2014) A conformational investigation of propeptide binding to the integral membrane protein ?-glutamyl carboxylase using nanodisc hydrogen exchange mass spectrometry. Biochemistry 53:1511-20
Boulaftali, Yacine; Hess, Paul R; Getz, Todd M et al. (2013) Platelet ITAM signaling is critical for vascular integrity in inflammation. J Clin Invest 123:908-16
Mutoh, Shingo; Sobhany, Mack; Moore, Rick et al. (2013) Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling. Sci Signal 6:ra31

Showing the most recent 10 out of 57 publications