- 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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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University of Pennsylvania
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Stalker, Timothy J; Welsh, John D; Brass, Lawrence F (2014) Shaping the platelet response to vascular injury. Curr Opin Hematol 21:410-7
Min, Sang H; Suzuki, Aae; Stalker, Timothy J et al. (2014) Loss of PIKfyve in platelets causes a lysosomal disease leading to inflammation and thrombosis in mice. Nat Commun 5:4691