Email this pageMorrell Lab
Research Focus
Platelets have two major functions: hemostastis/thrombosis and an immune regulatory function. My laboratory uses in vitro techniques and in vivo mouse models to study both important platelet functions.
Pathways of Platelet Activation and Thrombosis: We have recently discovered that platelets express ionotropic glutamate receptors including the AMPA and KA receptors. When stimulated platelets release glutamate that can mediate membrane depolarization, increase GPCR signaling, and thus make platelet activation and thrombosis more efficient. We have also recently discovered that platelet glutamate receptor signaling drives COX activation and the elaboration of thromboxane, contributing to a pro-thrombotic and inflammatory vascular environment. This work is continuing to be expanded to better understand glutamate regulation and signaling in the vasculature.
Immune Regulatory Role of Platelets: Platelets also have an important immune regulatory role that is not well defined. We have two main projects related to this platelet function; the role of platelets in transplant rejection and cerebral malaria.
We have established a skin transplant model to study platelet interactions with endothelial cells and leukocytes in transplant rejection. We have found that platelets accelerate vascular damage and leukocyte trafficking across transplant endothelium in response to alloantibody. This work is being expanded to more closely examine platelet interactions with T-cells and the role of platelet derived chemokines in transplant rejection.
Our lab is actively studying the role of platelets in cerebral malaria. Cerebral malaria is a complication of severe malaria, primarily in children, that has a vascular inflammation based pathogenesis. Using the mouse model we have established an important role for platelets and the platelet derived chemokine Platelet Factor 4 (PF4/CXCL4) in the development of experimental cerebral malaria. We are now dissecting the molecular signaling events between platelets and monocytes that help drive the cerebral immune response.
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