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 About Oral BiologyFaculty Info     June 29, 2016  

Russell, Michael M.A., Ph.D. Professor, Department of Microbiology and Immunology, Department of Oral Biology

111 Biomedical Research Building
Buffalo, NY 14214
(716)829-2790 - Faculty Home Page

Faculty Research Profile

My research is broadly concerned with the induction and functions of both secretory and circulating IgA antibodies, the immune response against bacterial infections especially of the oral cavity and genital tract, and novel approaches to mucosal vaccine development. We maintain that IgA antibodies are essentially anti-inflammatory, and can suppress damage to tissues arising from the inflammatory consequences of complement-dependent and opsono-phagocytic defense mechanisms. These concepts may be applicable to infection-driven inflammatory conditions such as periodontal disease, and coupled with strategies for mucosal immunization may offer novel approaches to the treatment of human disease.
Several years ago we developed a genetic strategy for coupling protein antigen segments to the highly immunogenic but non-toxic B subunit of cholera toxin (CTB) to make chimeric mucosal immunogens, and we have been investigating the mechanisms underlying the immune response to them. This approach was initially developed with surface protein adhesin AgI/II of Streptococcus mutans, an antigen that I discovered (along with AgIII) while working in London on a vaccine against dental caries. While I have maintained my interest in research towards a caries vaccine in collaboration with colleagues elsewhere, other applications of this approach to mucosal vaccine development include a vaccine against gonorrhea designed to elicit protective antibodies in the genital tract. We were among the first to show the efficacy of intranasal immunization for eliciting mucosal antibody responses in the genital tract as well as other secretions. In collaboration with Dr. Terry Connell, we have evaluated type II heat-labile enterotoxins as antigen-coupled delivery agents and adjuvants that have significantly different immunological properties from cholera toxin and may therefore be advantageous in vaccine development. The mechanisms by which these enterotoxins exert their immunomodulatory effects, the regulatory mechanisms involved, and the generation of memory within the mucosal immune system are being pursued. We are also exploring state-of-the-art imaging technology to follow the uptake of chimeric mucosal immunogens and enterotoxin adjuvants at mucosal inductive sites and characterize the antigen-presenting cells involved in the reponse to them.
We have also investigated human mucosal and systemic immune responses against Neisseria gonorrhoeae. As a result of these studies, we hypothesized that gonococci are capable of interfering with the normal course of an immune response, which may explain the paucity of antibodies developed during human gonorrhea, and the lack of effective immunity induced by natural exposure to it. We have found that Th17 cells are involved in the immune-inflammatory response to N. gonorrhoeae and are investigating their significance in a mouse model of this infection. In confirmation of our earlier hypothesis, we have now found that N. gonorrhoeae suppresses Th1- and Th2-driven adaptive immune responses through a mechanism involving TGF-beta and the generation of T-regulatory cells. In collaboration with other groups elsewhere we are also investigating possibilities for developing a mucosal vaccine against gonorrhea utilizing enterotoxins as immunomodulators or delivery agents for mucosal administration.

The Russell lab:
Weiwei Zhao, MD, PhD (Sun Yat-sen University, China)
Yingru Liu, MD, PhD (University of British Columbia, Canada)