- Core B The Thrombosis Models Core (Core B) will serve as a resource for all projects that include animal studies. The Core will provide the resources and expertise to facilitate the design, execution and interpretation of several thrombosis models. Among the models included are: 1) FeCl3 or rose Bengal-induced injury of the mouse carotid artery in which thrombus formation is monitored by measuring blood flow through the carotid artery using a Doppler flow probe;2) Laser, micropuncture, or rose Bengal-induced injury in the cremaster muscle microcirculation visualized in real-time by intravital microscopy;3) laser, FeCl3 or rose Bengal-induced injury of mouse mesenteric arteries or veins visualized by intravital microscopy;and 4) sytems to study platelet function ex vivo, including a flow chamber system and platelet aggregometer. A detailed description of each of these models including the molecular mechanisms involved and specific advantages of each is included in the description of Core B provided in this proposal. The physical resources necessary to conduct these studies (including the Doppler flow probe setup and confocal intravital microscopy system) are already in place. The core director, Dr. Timothy Stalker, has extensive experience performing in vivo thrombosis studies and will serve as a resource to all project investigators. In addition to standard thrombosis models, the core will also collaborate with project investigators to develop more advanced imaging techniques and additional thrombosis models that may then be utilized by all project investigators to advance their projects and increase our understanding of the spatio-temporal dynamics of hemostasis and thrombosis in vivo.

Public Health Relevance

- Core B Thrombosis is a major contributing factor to several pathological conditions including heart attacks and strokes that are among the leading causes of morbidity and mortality in the United States and throughout the developed world. The Thrombosis Models Core will be a major mechanism of integration among the projects in this program that has the overall goal of gaining a better understanding of the mechanisms responsible for thrombosis in order to advance new therapeutic strategies targeting this pathology.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL120846-01A1
Application #
8742308
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2014-08-08
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$208,500
Indirect Cost
$73,500
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Paul, David S; Casari, Caterina; Wu, Congying et al. (2017) Deletion of the Arp2/3 complex in megakaryocytes leads to microthrombocytopenia in mice. Blood Adv 1:1398-1408
Tomaiuolo, Maurizio; Brass, Lawrence F; Stalker, Timothy J (2017) Regulation of Platelet Activation and Coagulation and Its Role in Vascular Injury and Arterial Thrombosis. Interv Cardiol Clin 6:1-12
Zhao, Liang; Thorsheim, Chelsea L; Suzuki, Aae et al. (2017) Phosphatidylinositol transfer protein-? in platelets is inconsequential for thrombosis yet is utilized for tumor metastasis. Nat Commun 8:1216
Lee, Robert H; Bergmeier, Wolfgang (2017) Sugar makes neutrophils RAGE: linking diabetes-associated hyperglycemia to thrombocytosis and platelet reactivity. J Clin Invest 127:2040-2043
Shen, Jian; Sampietro, Sara; Wu, Jie et al. (2017) Coordination of platelet agonist signaling during the hemostatic response in vivo. Blood Adv 1:2767-2775
Kononova, Olga; Litvinov, Rustem I; Blokhin, Dmitry S et al. (2017) Mechanistic Basis for the Binding of RGD- and AGDV-Peptides to the Platelet Integrin ?IIb?3. Biochemistry 56:1932-1942
Welsh, J D; Poventud-Fuentes, I; Sampietro, S et al. (2017) Hierarchical organization of the hemostatic response to penetrating injuries in the mouse macrovasculature. J Thromb Haemost 15:526-537
Bennett, Joel S (2016) Shedding New Light on the Platelet Storage Lesion. Arterioscler Thromb Vasc Biol 36:1715-6
Zhu, S; Welsh, J D; Brass, L F et al. (2016) Platelet-targeting thiol reduction sensor detects thiol isomerase activity on activated platelets in mouse and human blood under flow. J Thromb Haemost 14:1070-81
Zhou, Zinan; Tang, Alan T; Wong, Weng-Yew et al. (2016) Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling. Nature 532:122-6

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