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
The focus of the lab is to understand the molecular basis of antigen-induced immune tolerance, the modulation of the innate immune system response in immunity against cancer, the role of extracellular adenosine in the regulation of central nervous system barrier permeability and gut epithelial barrier permeability. Ongoing projects in the lab are:
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.
Graduate Fields
Dr. Bynoe is a member of the following Graduate Fields:
Comparative Biomedical Sciences
Immunology
Lab Members
Jeff Mills, Postdoctoral Associate
Cindy Mueller, Technical Support
Related Links
Program in Infection and Pathobiology
Selected References
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., P. Bonorino, and C. Viret. 2007. Control of experimental autoimmune encephalomyelitis by CD4+ suppressor T cells:Peripheral versus in situ immunoregulation. J. Neuro. Immunol. 2007 Nov; 191(1-2):61-9.
Bynoe, M.S.1 and C. Viret2. 2008. Foxp3+CD4+ T cell-mediated immunosuppression involves extracellular nucleotide catabolism. Trends in Immunology. 29(3):99-102.
