- 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)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
United States
Zip Code
Fong, Karen P; Zhu, Hua; Span, Lisa M et al. (2016) Directly Activating the Integrin αIIbβ3 Initiates Outside-In Signaling by Causing αIIbβ3 Clustering. J Biol Chem 291:11706-16
Lee, R H; Bergmeier, W (2016) Platelet immunoreceptor tyrosine-based activation motif (ITAM) and hemITAM signaling and vascular integrity in inflammation and development. J Thromb Haemost 14:645-54
Stefanini, Lucia; Bergmeier, Wolfgang (2016) RAP1-GTPase signaling and platelet function. J Mol Med (Berl) 94:13-9
Lozano, María Luisa; Cook, Aaron; Bastida, José María et al. (2016) Novel mutations in RASGRP2, which encodes CalDAG-GEFI, abrogate Rap1 activation, causing platelet dysfunction. Blood 128:1282-9
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
Welsh, John D; Muthard, Ryan W; Stalker, Timothy J et al. (2016) A systems approach to hemostasis: 4. How hemostatic thrombi limit the loss of plasma-borne molecules from the microvasculature. Blood 127:1598-605
Geddings, J E; Hisada, Y; Boulaftali, Y et al. (2016) Tissue factor-positive tumor microvesicles activate platelets and enhance thrombosis in mice. J Thromb Haemost 14:153-66
Piatt, Raymond; Paul, David S; Lee, Robert H et al. (2016) Mice Expressing Low Levels of CalDAG-GEFI Exhibit Markedly Impaired Platelet Activation With Minor Impact on Hemostasis. Arterioscler Thromb Vasc Biol 36:1838-46
Ivanciu, L; Stalker, T J (2015) Spatiotemporal regulation of coagulation and platelet activation during the hemostatic response in vivo. J Thromb Haemost 13:1949-59
Sayani, Farzana A; Abrams, Charles S (2015) How I treat refractory thrombotic thrombocytopenic purpura. Blood 125:3860-7

Showing the most recent 10 out of 28 publications