Craig Morrell, D.V.M., Ph.D.
Associate Professor, Department of Medicine, Aab Cardiovascular Research Institute
2005 | PhD | Pathobiology | The Johns Hopkins U Sch Medicine
2000 | DVM | Veterinary Medicine | Tufts University Sch of Veterinary Med
1995 | Sc.B | Biology | Brown University
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.
- P90RSK Targets the ERK5-CHIP Ubiquitin E3 Ligase Activity in Diabetic Hearts and Promotes Cardiac Apoptosis and Dysfunction., Le NT, Takei Y, Shishido T, Woo CH, Chang E, Heo KS, Lee H, Lu Y, Morrell C, Oikawa M, McClain C, Wang X, Tournier C, Molina CA, Taunton J, Yan C, Fujiwara K, Patterson C, Yang J, Abe JI., Circ Res. 2012 Jan 19.
- Associations of large artery structure and function with adiposity: Effects of age, gender, and hypertension. The SardiNIA Study., Scuteri A, Orru' M, Morrell CH, Tarasov K, Schlessinger D, Uda M, Lakatta EG., Atherosclerosis. 2011 Dec 14.
- Immunomodulatory mediators in platelet transfusion reactions., Morrell CN., Hematology Am Soc Hematol Educ Program. 2011;2011:470-4.
- Association of Frontal QRS-T Angle-Age Risk Score on Admission Electrocardiogram With Mortality in Patients Admitted With an Acute Coronary Syndrome., Lown MT, Munyombwe T, Harrison W, West RM, Hall CA, Morrell C, Jackson BM, Sapsford RJ, Kilcullen N, Pepper CB, Batin PD, Hall AS, Gale CP; Evaluation of Methods and Management of Acute Coronary Events (EMMACE) Investigators., Am J Cardiol. 2012 Feb 1;109(3):307-13.
- An assessment of the concentration-related prognostic value of cardiac troponin I following acute coronary syndrome., Gale CP, Metcalfe E, West RM, Das R, Kilcullen N, Morrell C, Crook R, Batin PD, Hall AS, Barth JH., Am J Cardiol. 2011 Nov 1;108(9):1259-65.