The University of Michigan School of Dentistry
Dr. Fenno's research focuses on the role of the oral spirochete T. denticola in the development of periodontal diseases. The studies involve molecular characterization of spirochete surface-expressed and secreted proteins and their interactions with host tissue components. These studies, which involve both genetic and biochemical analyses, will contribute to the understanding of microbe-host interactions in the etiology of periodontal diseases, as well as to basic knowledge of the molecular biology of pathogenic spirochetes.
The predominance of spirochetes in subgingival plaque associated with severe periodontal lesions suggests an important role in periodontal pathogenesis. The goal of this research is to characterize interactions of Treponema denticola with subgingival tissues at the molecular level. By focusing on analysis of surface-expressed proteins that directly affect host cells, insights will be gained into mechanisms of periodontal cytopathology. The major outer membrane protein (Msp) of T. denticola binds to cells and ECM components, and has pore-forming cytotoxic actiyity. Msp is genetically conserved in many oral spirochetes, yet shows considerable interstrain heterogeneity, suggesting that it is an important immunogen. The overall hypothesis is that Msp is a significant virulence determinant in periodontal disease, and is a key component of an outer membrane protein complex mediating interactions of the spirochete with subgingival tissue.
Specific aims of the proposed research, and the individual hypotheses to be tested are:
These studies, which involve both genetic and biochemical analyses, should contribute significantly to the understanding of microbe-host interactions in the etiology of periodontal diseases, as well as to basic knowledge of the molecular biology of pathogenic spirochetes.
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Dr. Fenno received his Ph.D. in the Department Microbiology and Molecular Genetics, University of Vermont in 1993. Prior to coming to the University of Michigan, he was a Postdoctoral Fellow and Research Associate in the Department of Microbiology and Immunology at the University of British Columbia in Vancouver, Canada. Dr. Fenno joined the Department of Biologic and Materials Sciences at the University of Michigan in 1998.
Recent development of molecular genetic techniques and improved culturing methods have had a major impact on the study of the role of the microbes in periodontal disease. The ability to characterize specific pathogenic effects and behaviors permits molecular level analysis of the interactions between subgingival plaque bacteria and host tissue destruction and bone loss. This approach, known as cellular microbiology, is a rapidly developing research area in infectious diseases.
Dr. Fenno's research focuses in the role of oral spirochetes in periodontal diseases. These oral anaerobic bacteria, most notably Treponoma denticola, have long been associated with severe periodontal diseases. Of particular interest are T. denticola proteases and other surface proteins that have cytotoxic or immunomodulatory effects. The studies involve molecular characterization of spirochete outer membrane proteins and their interactions with host tissue components.
Dr. Fenno's work has contributed to molecular level genetic and functional analysis of T. denticola surface proteins as potential periodontal virulence factors. Partly as a result of this work, T. denticola has become an attractive model for the study of spirochete-host interactions in medically significant spirochetoses of medical significance including syphilis and Lyme disease.