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.
|Klann, Jane E; Kim, Stephanie H; Remedios, Kelly A et al. (2018) Integrin Activation Controls Regulatory T Cell-Mediated Peripheral Tolerance. J Immunol 200:4012-4023|
|Griffin, John H; Zlokovic, Berislav V; Mosnier, Laurent O (2018) Activated protein C, protease activated receptor 1, and neuroprotection. Blood 132:159-169|
|Sinha, Ranjeet K; Wang, Yaoming; Zhao, Zhen et al. (2018) PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke. Blood 131:1163-1171|
|Xu, Xiaohong Ruby; Wang, Yiming; Adili, Reheman et al. (2018) Apolipoprotein A-IV binds ?IIb?3 integrin and inhibits thrombosis. Nat Commun 9:3608|
|Gupta, Naveen; Liu, Roland; Shin, Stephanie et al. (2018) SCH79797 improves outcomes in experimental bacterial pneumonia by boosting neutrophil killing and direct antibiotic activity. J Antimicrob Chemother 73:1586-1594|
|Gupta, Naveen; Sinha, Ranjeet; Krasnodembskaya, Anna et al. (2018) The TLR4-PAR1 Axis Regulates Bone Marrow Mesenchymal Stromal Cell Survival and Therapeutic Capacity in Experimental Bacterial Pneumonia. Stem Cells 36:796-806|
|Amar, Arun Paul; Sagare, Abhay P; Zhao, Zhen et al. (2018) Can adjunctive therapies augment the efficacy of endovascular thrombolysis? A potential role for activated protein C. Neuropharmacology 134:293-301|
|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|
|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|
|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|
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