Core A will continue to provide standardized procedures for the quantitative study of processes relevant to thrombus formation and regulation using In vivo models in the murine circulation and ex vivo models in perfusion chambers under the influence of defined flow forces. Core A will also perform isolation, culture and characterization of relevant vascular cells. Project 1 (Griffin;39% use) will utilize primarily in vivo models to study the antithrombotic properties of wild type and mutant activated protein C and protein S. Project 2 (Ginsberg;22% use) will utilize in vivo models to study the arterial thrombogenic phenotype resulting from functional alterations of CD98, as well as ex vivo models to study the thrombogenic potential of smooth muscle cells derived from the same mutant mice. Project 3 (Ruf;39% use) will utilize in vivo models of response to vascular injury to explore the mechanisms leading to the induction of tissue factor activity, as well as complementary ex vivo fiow models to explore the mechanisms of tissue factor decryption in relevant vascular cells under more constrained experimental conditions.

Public Health Relevance

Core A will ensure uniformity of methodological approach with respect to the use of key experimental models that will be crucial to validate the in vivo relevance of the results obtained by the individual projects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL031950-29
Application #
8686044
Study Section
Heart, Lung, and Blood Program Project Review Committee (HLBP)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
29
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Griffin, John H; Mosnier, Laurent O; Fernández, José A et al. (2016) 2016 Scientific Sessions Sol Sherry Distinguished Lecturer in Thrombosis: Thrombotic Stroke: Neuroprotective Therapy by Recombinant-Activated Protein C. Arterioscler Thromb Vasc Biol 36:2143-2151
Ruf, Wolfram; Rothmeier, Andrea S; Graf, Claudine (2016) Targeting clotting proteins in cancer therapy - progress and challenges. Thromb Res 140 Suppl 1:S1-7
Schmidt, Thomas; Ye, Feng; Situ, Alan J et al. (2016) A Conserved Ectodomain-Transmembrane Domain Linker Motif Tunes the Allosteric Regulation of Cell Surface Receptors. J Biol Chem 291:17536-46
Deguchi, Hiroshi; Banerjee, Yajnavalka; Elias, Darlene J et al. (2016) Elevated CETP Lipid Transfer Activity is Associated with the Risk of Venous Thromboembolism. J Atheroscler Thromb 23:1159-1167
Burnier, Laurent; Boroujerdi, Amin; Fernández, Jose A et al. (2016) Physiological cerebrovascular remodeling in response to chronic mild hypoxia: A role for activated protein C. Exp Neurol 283:396-403
Bhat, Vikas; von Drygalski, Annette; Gale, Andrew J et al. (2016) Improved coagulation and haemostasis in haemophilia with inhibitors by combinations of superFactor Va and Factor VIIa. Thromb Haemost 115:551-61
Alsultan, Abdulrahman; Gale, Andrew J; Kurban, Kadijah et al. (2016) Activation-resistant homozygous protein C R229W mutation causing familial perinatal intracranial hemorrhage and delayed onset of thrombosis. Thromb Res 143:17-21
Abplanalp, Wesley T; Conklin, Daniel J; Cantor, Joseph M et al. (2016) Enhanced Integrin α4β1-Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes. Diabetes :
Wang, Yaoming; Zhao, Zhen; Rege, Sanket V et al. (2016) 3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice. Nat Med 22:1050-5
Deguchi, Hiroshi; Sinha, Ranjeet K; Marchese, Patrizia et al. (2016) Prothrombotic skeletal muscle myosin directly enhances prothrombin activation by binding factors Xa and Va. Blood :

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