Assistant Professor, Department of Molecular and Comparative Pathobiology
Background and Training
ScB Brown University 1995
DVM Tufts University 2000
PhD Johns Hopkins University 2005
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, such as the AMPA receptor, that when glutamate bound mediate membrane depolarization, increased GPCR signaling, and thus more efficient platelet activation and thrombosis (recently accepted at The Journal of Experimental Medicine). This work is continuing to be expanded to better understand glutamate regulation and signaling in the vasculature.
Immune Regulatory Role of Platelets: Platelets have a less well explored immune regulatory role. We have two main projects related to this important platelet function; platelets in transplant rejection and cerebral malaria.
We have established a skin transplant model to study platelet interactions with endothelial cells and leukocytes in response to alloantibody. We have found that platelets accelerate vascular damage and leukocyte trafficking across transplant endothelium in response to alloantibody (recently accepted at Circulation Research). 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 platelet derived chemokines in the development of experimental cerebral malaria.
Selected Publications
Morrell CN, Sun H, Mason EA, Martin TV, Swaim AM, Gozen O, Beique JC, Ampagoomian D, Sprengel R, Rothstein JD, Faraday N, Huganir RL, Lowenstein CJ. “Glutamate Mediates Platelet Activation Through the AMPA Receptor” The Journal of Experimental Medicine.
Morrell CN, Mason EA, Martin TV, Swaim AM, Ballard M, Murata K, Baldwin WM. “Alloantibodies to MHC Induce Platelet-Endothelial Cell Interactions” Circulation Research.
Morrell CN, Sun H, Swaim AM, Baldwin WM 3rd. Platelets an inflammatory force in transplantation. American Journal of Transplantation November 2007;7(11):2447-54.
Matsushita K, Morrell CN, Mason RJ, Yamakuchi M, Khanday FA, Irani K, Lowenstein CJ. “Hydrogen peroxide regulation of endothelial exocytosis by inhibition of N-ethylmaleimide sensitive factor” Journal of Cell Biology. July 4, 2005;170(1):73-9.
Morrell CN, Matsushita K, Chiles K, Scharpf RB,Yamakuchi M, Mason RJA, Bergmeier W, Mankowski JL, Baldwin WM, Faraday N, Lowenstein CJ. “Regulation of Platelet Granule Exocytosis by S-Nitrosylation” Proceeding National Academy of Science March 8, 2005;102(10):3782-7.
Morrell CN, Matsushita K, Lowenstein CJ. “A Novel Inhibitor of N-Ethylmaleimide Sensitive Factor Decreases Vascular Inflammation and Peritonitis” Journal of Pharmacology and Experimental Therapeutics. July, 2005; 314(1):155-61.
Matsushita K, Morrell CN, Lowenstein CJ. “A Novel Class of Fusion Polypeptides Inhibits Exocytosis” Molecular Pharmacology. April, 2005;67(4):1137-44.
Matsushita K, Morrell CN, Cambien B, Yang SX, Yamakuchi M, Bao C, Hara MR, Quick RA, Cao W, O'Rourke B, Lowenstein JM, Pevsner J, Wagner DD, Lowenstein CJ.“Nitric Oxide Regulates Exocytosis by S-Nitrosylation of N-ethylmaleimide-Sensitive Factor.” Cell October 17, 2003, Vol. 115(2):139-50.
Chen W, Carter MG, Zeng X, Morrell CN, Esteller M, Walkins ND, Herman JG, Mankowski JL, and Baylin S. “Heterozygous Disruption of Hic-1 Predisposes Mice to a Gender-dependent Spectrum of Malignant Tumors.” Nature Genetics, February, 2003, Vol. 33(2):197-202.
Mathiowitz, E., Jacob, J., Jong, Y., Carino, G., Chickering, D., Chaturvedi, P., Santos, C., Vijayaraghavan, K., Montgomery, S., Bassett, M., Morrell, C. “Biologically Erodable Microspheres as Potential Oral Drug Delivery Systems.” Nature, March 27, 1997, Vol.386, 410-414.
