Discovering

INDIVIDUAL RESEARCHER

Edmund J. Gosselin , Ph.D.
Professor
e-mail: gossele@mail.amc.edu

Education

1988 - Ph.D. from the University of Massachusetts Medical Center

Current Research

The primary focus of research in my laboratory is in the area of antigen (Ag) processing and presentation. Ag presentation is a critical component of an effective immune response against most pathogens. The basic tenet of research in my laboratory is that by better understanding Ag processing and presentation, the cell types involved, and mechanisms for enhancing Ag presentation, one can more effectively manipulate the immune response, and ultimately patient outcome.

It has been known since the mid 1980's that Ag bound to antibody (Ab) in the form of soluble Ag-Ab complexes is presented by Fc receptor-bearing Ag presenting cells to Ag- specific T cells approximately 100 fold more efficiently than Ag alone. While current funding in my laboratory is directed at understanding these and other issues related to Fc receptor- dependent enhancement of Ag presentation by mouse and human monocytes, macro- phages and dendritic cells, the ultimate goal of this laboratory is to convert knowledge gained from these studies into clinical application.

Our studies, and those of other laboratories, indicate that targeting Ag to Ag presenting cells can significantly enhance T cell activation in vitro. Using human Fc gamma receptor type I transgenic mice we have also shown that targeting antigen to human Fc gamma receptor type I, in vivo, can significantly enhance both Ab and cytokine responses, while also eliminating the need for traditional adjuvant. Most recently, we have further demonstrated that targeting Ag to Fc receptors on Ag presenting cells in the absence of adjuvant, at a mucosal site, enhances protection against subsequent mucosal challenge with infectious agents.

Thus, the current focus of the laboratory is on the development of adjuvant-independent vaccines through Fc receptor targeting of Ag at mucosal sites. In particular, as it applies to mouse and human immune responses to Francisella tularensis (a category A biothreat agent), Streptococcus pneumoniae (a common respiratory pathogen) and HIV (a deadly viral pathogen). Ultimately, we expect these studies, and this vaccine strategy, will have wide applicability to vaccines against a variety of pathogens in adult, pediatric, and immuno- compromised populations.

How We Currently Believe Fc Receptor Targeting of Immunogens Works at Mucosal Sites

References

1. Gosselin, E..J., Gosselin, D.R. and Lotz, S.A. Natural Killer and CD8 T Cells Dominate the Response by Human Peripheral Blood Mononuclear Cells to Inactivated Francisella tularensis Live Vaccine Strain. Hum Immunol. 66:1039-49, 2005.



2. Adamova, E., Walsh, M.C., Gosselin, D.R., Hale, K., Preissler, M.T., Graziano, R.F. and Gosselin, E.J. Enhanced Antigen-Specific Antibody and Cytokine Responses When Targeting Antigen to Human FcGAMMA Receptor Type I Using an Anti-Human FcGAMMA Receptor Type I- Streptavidin Fusion Protein in an Adjuvant-Free System. Immunol Invest. 34(4):417-29, 2005.



3. Rawool, D,. Bitsaktsis, C., Li, Y., Gosselin, D.R., Lin, Y., Kurkure, N.V., Metzger, D.W. and Gosselin, E..J. Utilization of Fc receptors as a Mucosal Vaccine Strategy Against an Intracellular Bacterium, Francisella tularensis, J Immunol. 180(8):5548-57, 2008.



4. Bitsaktsis, C., Rawool, R.B., Li, Y., Kurkure, N.V., Iglesias, B. and Gosselin, E.J. Differential Requirements for Protection against Mucosal Challenge with Francisella tularensis in the Presence Versus Absence of Cholera Toxin B and Inactivated F. tularensis. J Immunol, 180: 5548-5557, 2009.



5. Gosselin, E.J., Bitsaktsis, C., Li, Y. and Iglesias, B. Fc Receptor-Targeted Mucosal Vaccination as a Novel Strategy for the Generation of Enhanced Immunity Against Mucosal and Non- Mucosal Pathogens. Archives of Immunology and Experimental Therapy. 57, 311-323, 2009.