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 publications, contact information Research Interests My laboratory is interested in different aspects of innate immunity, in the context of infectious disease and inflammation. The following projects are currently ongoing: 1. Hookworm secretion in host immunomodulation: We have recently identified a protein(s) secreted by hookworm parasites that binds selectively to human natural killer (NK) cells and induces them to secrete high levels of IFNg. Studies are currently underway to further investigate the interaction of this NK cell binding protein (NKBP) with other subsets of leukocytes, as well as characterize and clone NKBP. In addition, we are investigating the binding and effect of NKBP on leukocytes from patients with active hookworm infections in Brazil to establish the physiologic contribution of this protein(s) to the maintenance of chronic infection. This project is being conducted in collaboration with Drs. Jeff Bethony and Alex Loukas. 2. Cyclophilins in inflammation: Extracellular cyclophilins have recently been shown to have potent chemotactic properties, suggesting a role for leukocyte recruitment during inflammatory responses. We are investigating the contribution of these cyclophilins to leukocyte migration in different inflammatory diseases, including rheumatoid arthritis, acute lung inflammation and asthma. Animal models for each of these inflammatory diseases have been established within the laboratory and are being used to assess the impact of inhibition extracellular cyclophilins on tissue inflammation and pathology. In addition, we are investigating the interaction between extracellular cyclophilins and other chemokines known to be present during inflammatory responses. This project is being conducted in collaboration with Dr. Michael Bukrinsky. Selected Publications Top Damsker, J., M. Bukrinsky and S. Constant. 2007. Extracellular cyclophilin A induces CD147-dependent migration of human CD4 + T lymphocytes. J. Leuk. Biol. in press. Yamashita, Y., N. Charles, Y. Furumoto, S. Odom, T. Yamashita, A. Gilfillan, S. Constant, M. Bower, J. Ryan and J. Rivera. 2007. Cutting Edge: Genetic variation influences Fc e RI-induced mast cell activation and allergic responses. J. Immunol. 179:740-743. Wolnicka-Glubisz, A., J. Damsker, S. Constant, S. Corn, E. De Fabo and F. Noonan. 2007. Deficient inflammatory response to UVB in neonatal mice. J. Leuk. Biol. 81:1352-1361. Gwinn, W., J. Damsker, R. Falahati, I. Okwumabua, A. Kelly-Welsh, A. Keegan, C. Vanpouille, J. Lee, L. Dent, D. Leitenberg, M. Bukrinsky and S. Constant. 2006. Novel approach to inhibit asthma-mediated lung inflammation using anti-CD147 intervention. J. Immunol. 177:4870-4879. Cormier, S., A. Taranova, C. Bedient, T. Nguyen, C. Protheroe, R. Pero, D. Dimina, S. Ochkur, K. O’Neill, D. Colbert, T. Lombari, S. Constant, M. McGarry, J. Lee and N. Lee. 2006. Eosinophil infiltration of solid tumors is an early and persistent inflammatory host response. J. Leuk. Biol. 79: 1131-1139. Yurchenko, V., S. Constant and M. Bukrinsky. 2005. Dealing with the Family: CD147 interactions with cyclophilins. Immunology 117:301-309 Loukas, A., S. Constant and J. Bethony. 2005. Immunobiology of hookworm infection. FEMS: Immunology and Microbiology 43:115-124. Arora, K., W. Gwinn, M. Bower, A. Watson, I. Okwumabua, R. MacDonald, M. Bukrinsky and S. Constant. 2005. Extracellular cyclophilins contribute to the regulation of inflammatory responses. J. Immunol. 175:517-522. Piggott, D., S. Eisenbarth, L. Xu, S. Constant, J. Huleatt, C. Herrick and K. Bottomly. 2005. MyD88 dependent induction of allergic Th2 responses to inhaled antigen. J. Clin. Invest. 115:459-467. Hsieh, G., A. Loukas, A. Wahl, M. Bhatia, Y. Wang, A. Williamson, K. Kehn, H. Maruyama, P. Hotez, D. Leitenberg, J. Bethony and S. Constant. 2004. A secreted protein from the human hookworm Necator americanus binds selectively to NK cells and induces IFN- production. J. Immunol. 173:2699-2704. Palmer, G., J. Brogdon, S. Constant and P. Tattersall. 2004. A non-proliferating parvoviral vaccine vector elicits sustained, protective humoral immunity following a single intravenous or intranasal inoculation. J. Virol. 78:1101-1108. Contact Information Top The George Washington University Medical Center
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