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Dr. Margaret Bynoe, an Assistant Professor in the Department of Microbiology and Immunology, received her Bachelor of Science in Biology from the Long Island University and her PhD from the Albert Einstein College of Medicine. She received her postdoctoral training and became an Associate Research Scientist at Yale University School of Medicine. Research Interests | Graduate Fields | Lab Members | Related Links | Selected References Research Interests 1) To study the mechanism of self antigen-specific immune tolerance induction in experimental autoimmune encephalomyelitis (EAE) by epicutaneous immunization. EAE is the animal model for multiple sclerosis, an autoimmune disease of the central nervous system (CNS) mediated by proinflammatory immune cells that infiltrate the CNS and mount immune responses against myelin components, resulting in neuronal damage that can cause paralysis and even death. Epicutaneous immunization or skin patching is the application of a patch soaked in pure self-antigen to the shaved skin of mice prior to inducing disease with the same antigen. We were able to induce tolerance in several EAE animal models. We are now applying the epicutaneous mode of antigen delivery to determine whether we can abort ongoing EAE. 2) Inducing tumor antigen-specific immunity. This project entails applying the epicutaneous mode of antigen delivery to induce antigen-specific tumor immunity by varying the antigenic environment in the skin patch. This is based on our previous findings that suggest that varying the antigen environment in the patch results in different immune outcome favorable to eradicating tumors. 3) We are investigating the role of extracellular adenosine, that is, adenosine generated by CD73 (Ecto-5'-nucleotidase), a glycosyl phosphatidylinositol (GPI)-linked membrane protein that catalyzes the extracellular dephosphorylation of AMP to adenosine. Preliminary evidence demonstrates that CD73 generated adenosine is required for efficient lymphocyte migration into the CNS, and for EAE development. We are investigating the mechanism of adenosine-induced protection against EAE development and CNS barrier permeability.
4) As a potent endogenous modulator, CD73-generated adenosine regulates the function and differentiation of epithelial, endothelial and immune cells in the intestinal lumen as its levels increase during inflammation. Mice deficient in the CD73 molecule developed a very severe colitis that has very strong correlates with Chron's disease compared to their wild type counterparts. We are interested in the factors that govern intestinal epithelial permeability that adenosine might be acting on.
Dr. Bynoe is a member of the following Graduate Fields:
Leah Alabanza, Graduate Student
Bynoe, M., T.J. Evans, C. Viret, and C.A. Janeway Jr. 2003. Epicutaneous immunization with an autoantigen induces T suppressor cells that prevent experimental allergic encephalomyelitis. Immunity. 19:317-328. Recognized by Faculty of 1000 Bynoe, M. 2004. Epidermal Antigen Presenting Cells are Tolerogenic Under Conditions of Skin Immunization with Self-peptide. Immunology. International Proceedings. MEDIMOND. 88:7587-069-1. Bynoe, M., C. Viret, R.A. Flavell, and C.A. Janeway Jr. 2005. T cells from epicutaneously immunized mice are prone to T cell receptor revision. Proc. Natl. Acad. Sci. USA. 102:2898-2903. Bynoe, M. and C. Viret. 2005. Antigen-induced Suppressor T cells from the skin point of view:Suppressor T Cells Induced Through Epicutaneous Immunization. J. Neuro. Immunol. 167:4-12. Bynoe, M.S. and C. Viret. 2008. Foxp3+CD4+ T cell-mediated immunosuppression involves extracellular nucleotide catabolism. Trends in Immunology. 29:99-102. Mills, J.H., L.F. Thompson, C. Mueller, A.T. Waickman*, S. Jalkanen, J. Niemela, L. Airas§, and M.S. Bynoe. 2008. CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA. 105:9325-9330. |
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