Lab Research Focus
Dr. Suzanne Michalek and her associates have focused their research on mucosal vaccine development and on mechanisms involved in the induction of mucosal immune responses (including responses in the respiratory, gastrointestinal and urogenital tracts and the oral cavity) or of inflammatory responses. Current studies are investigating vectors (e.g., avirulent Salmonella or liposomes) and adjuvants for their use in the development of mucosal vaccines. These studies are being done in humans and experimental animal models. Current studies in humans are testing the effectiveness of mucosal vaccines consisting of a recombinant microbial antigen from Streptococcus mutans and adjuvants in inducing mucosal and systemic immune responses. Studies are also planned to test this vaccine in children to determine its effectiveness in inducing mucosal responses protective against dental caries. Concurrent studies in vitro are investigating the host's cell surface receptors (including the co-stimulatory molecules and the Toll-like receptors) and signaling pathways involved in the host's recognition of the microbial virulence factor when expressed by the recombinant, avirulent Salmonella vector vaccine and the resulting response. These studies should define improved safe ways to elicit protective responses with mucosal-based vaccines. We are also using these approaches for the development of mucosal vaccines against biodefense agents, i.e., Francisella tularensis, where the route of infection would be inhalation or ingestion. Other studies involve immunologic, molecular biology and cell biology approaches to define microbial components and host factors involved in periodontal disease. In vivo and in vitro models are being used to define virulence factors of the periodontal pathogen Porphyromonas gingivalis, which are likely involved in microbial adherence and invasion of the epithelial barrier. Other studies are investigating the cellular mechanisms involve in the ability of this gram-negative bacterium or its components to mediate inflammatory responses and subsequent periodontal bone loss. These studies also are assessing the role of the Toll-like receptors and the co-stimulatory molecules in responses. The cell types and signaling pathways involved in mediating an inflammatory response, as well as bone loss are also being investigated. We are also looking at the role of the vitamin D receptor in these processes. Finally, other studies are using the information gained in understanding microbial-host interactions at the cellular level to develop immunotherapeutic approaches to protect against infectious and inflammatory diseases.
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