The specific proteolytic activation steps of blood coagulation are catalyzed by serine proteinases that are homologous to each other and to the archetypal serine proteinases

Public Health Relevance

The formation of a blood clot results from a series of very specific activation steps in which an inactive precursor in blood is cleaved at specific sites to form an active product. Our research is directed towards obtaining new insights into how these reactions of high specificity occur. The findings will reveal novel strategies for interfering with these reactions and for the treatment of life-threatening blood clots associated with a variety of human diseases

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL074124-10
Application #
8450261
Study Section
Special Emphasis Panel (ZHL1-PPG-J)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
10
Fiscal Year
2013
Total Cost
$466,814
Indirect Cost
$183,037
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Vadivel, Kanagasabai; Kumar, Yogesh; Bunce, Matthew W et al. (2017) Interaction of factor V B-domain acidic region with its basic region and with TFPI/TFPI2: Structural insights from molecular modeling studies. Int Biol Rev 1:
Thalji, Nabil K; Ivanciu, Lacramioara; Davidson, Robert et al. (2016) A rapid pro-hemostatic approach to overcome direct oral anticoagulants. Nat Med 22:924-32
Bradford, Harlan N; Krishnaswamy, Sriram (2016) The Fragment 1 Region of Prothrombin Facilitates the Favored Binding of Fragment 12 to Zymogen and Enforces Zymogen-like Character in the Proteinase. J Biol Chem 291:11114-23
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Pickens, Brandy; Mao, Yingying; Li, Dengju et al. (2015) Platelet-delivered ADAMTS13 inhibits arterial thrombosis and prevents thrombotic thrombocytopenic purpura in murine models. Blood 125:3326-34
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Baroni, M; Pavani, G; Pinotti, M et al. (2015) Asymmetric processing of mutant factor X Arg386Cys reveals differences between intrinsic and extrinsic pathway activation. Biochim Biophys Acta 1854:1351-6
George, L A; Thalji, N K; Raffini, L J et al. (2015) Correction of human hemophilia A whole blood abnormalities with a novel bypass agent: zymogen-like FXa(I16L). J Thromb Haemost 13:1694-8

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