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.
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.
|Subramaniam, Saravanan; Jurk, Kerstin; Hobohm, Lukas et al. (2017) Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development. Blood 129:2291-2302|
|Kamikubo, Yuichi; Mendolicchio, G Loredana; Zampolli, Antonella et al. (2017) Selective factor VIII activation by the tissue factor-factor VIIa-factor Xa complex. Blood 130:1661-1670|
|Amar, Arun Paul; Sagare, Abhay P; Zhao, Zhen et al. (2017) Can adjunctive therapies augment the efficacy of endovascular thrombolysis? A potential role for activated protein C. Neuropharmacology :|
|Klann, Jane E; Remedios, Kelly A; Kim, Stephanie H et al. (2017) Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool. J Immunol 198:4639-4651|
|Rothmeier, Andrea S; Marchese, Patrizia; Langer, Florian et al. (2017) Tissue Factor Prothrombotic Activity Is Regulated by Integrin-arf6 Trafficking. Arterioscler Thromb Vasc Biol 37:1323-1331|
|Deguchi, Hiroshi; Navarro, Silvia; Payne, Amanda B et al. (2017) Low level of the plasma sphingolipid, glucosylceramide, is associated with thrombotic diseases. Res Pract Thromb Haemost 1:33-40|
|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|
|Ruf, Wolfram; Rothmeier, Andrea S; Graf, Claudine (2016) Targeting clotting proteins in cancer therapy - progress and challenges. Thromb Res 140 Suppl 1:S1-7|
|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|
|Abplanalp, Wesley T; Conklin, Daniel J; Cantor, Joseph M et al. (2016) Enhanced Integrin ?4?1-Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes. Diabetes 65:3505-3515|
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