My research program is focused on the molecular mechanisms of pathogenesis of Porphyromonas gingivalis (P. gingivalis), a bacterium that is associated with adult periodontitis and recently reported to be involved in cardiovascular disease. There are several major areas of investigation at the molecular level which are funded by three grants from the National Institute for Dental and Craniofacial Research. The longest running funded project was originally aimed at discovering the surface antigens that allow P. gingivalis to adhere to host oral tissues, thereby creating a niche for disease progression. Results of work subsequent to the cloning and expression of a family of five surface antigens called hemagglutinins has revealed an integral role for these proteins in the establishment and progression of human disease. The research program continues to study the pathogenic role of these hemagglutinins through the creation of isogenic mutants with subsequent molecular, biochemical, and tissue culture analysis. With the recent indictment of P. gingivalis as a contributor to cardiovascular disease, the laboratory started investigating the mechanisms by which P. gingivalis interacts with and invades human cardiovascular arterial endothelial cells. Microarray analysis has been conducted in conjunction with these adhesion/invasion assays to determine the gene expression profile of P. gingivalis during the adhesion/invasion process. Finally, the research program is using a new technology called In Vitro Induced Antigen Technology, or IVIAT, to discover new P. gingivalis virulence genes. The IVIAT technology provides a method of finding out which P. gingivalis genes are expressed while causing disease in the human host rather than in an in vitro (test tube) or animal model. By identifying virulence-associated genes that would not be found by conventional methods we will improve our understanding of the pathogenic mechanisms employed by P. gingivalis. We expect that these newly-identified genes and their products will be excellent candidates for therapeutic, diagnostic, and vaccine-design targets.
- Song, H., Belanger, M., Whitlock, J., Kozarov, E., & Progulske-Fox, A. (2005). Hemagglutinin B is involved in the adherence of Porphyromonas gingivalis to human coronary artery endothelial cells. Infect Immun., 73(11), 7267-73.
- Rodrigues, P.H., & Progulske-Fox, A. (2005). Gene expression profile analysis of Porphyromonas gingivalis during invasion of human coronary artery endothelial cells. Infect Immun., 73(9), 6169-73.
- Yuan, L., Hillman, J.D., & Progulske-Fox, A. (2005). Microarray analysis of quorum-sensing-regulated genes in Porphyromonas gingivalis. Infect Immun., 73(7), 4146-54.
- Handfield, M., Mans, J.J., Zheng, G., Lopez, M.C., Mao, S., Progulske-Fox, A., Narasimhan, G., Baker, H.V., & Lamont, R.J. (2005). Distinct transcriptional profiles characterize oral epithelium-microbiota interactions. Cell Microbiol., 7(6), 811-23.
- John, M., Kudva, I.T., Griffin , R.W., Dodson, A.W., McManus, B., Krastins, B., Sarracino, D., Progulske-Fox, A., Hillman, J.D., Handfield, M., Tarr, P.I., & Calderwood, S.B. (2005). Use of in vivo-induced antigen technology for identification of Escherichia coli O157:H7 proteins expressed during human infection. Infect Immun., 73(5), 2665-79.
- Kozarov, E.V., Dorn, B.R., Shelburne, C.E., Dunn, W.A. Jr, & Progulske-Fox, A. (2005). Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Arterioscler Thromb Vasc Biol., 25(3), e17-8.
- Cwikla, S.J., Belanger, M., Giguere, S., Progulske-Fox, A., & Vertucci, F.J. (2005). Dentinal tubule disinfection using three calcium hydroxide formulations. J Endod., 31(1), 50-2.
- Handfield, M., Progulske-Fox, A., & Hillman, J.D. (2000). In vivo induced genes in human diseases. Periodontol 2000, 38, 123-34.
- Cao, S.L., Progulske-Fox, A., Hillman, J.D., & Handfield, M. (2004). In vivo induced antigenic determinants of Actinobacillus actinomycetemcomitans. FEMS Microbiol Lett., 237(1), 97-103.
- Kim, Y.R., Lee, S.E., Kim, C.M., Kim, S.Y., Shin, E.K., Shin, D.H., Chung, S.S., Choy, H.E., Progulske-Fox, A., Hillman, J.D., Handfield, M., & Rhee, J.H. (2003). Characterization and pathogenic significance of Vibrio vulnificus antigens preferentially expressed in septicemic patients. Infect Immun., 71(10), 5461-71.
- Hang, L., John, M., Asaduzzaman, M., Bridges, E.A., Vanderspurt, C., Kirn, T.J., Taylor , R.K., Hillman, J.D., Progulske-Fox, A., Handfield, M., Ryan, E.T., & Calderwood, S.B. (2003). Use of in vivo-induced antigen technology (IVIAT) to identify genes uniquely expressed during human infection with Vibrio cholerae. Proc Natl Acad Sci U S A, 100(14), 8508-13.
- Cheng, S., Clancy, C.J., Checkley, M.A., Handfield, M., Hillman, J.D., Progulske-Fox, A., Lewin, A.S., Fidel, P.L., & Nguyen, M.H. (2003). Identification of Candida albicans genes induced during thrush offers insight into pathogenesis. Mol Microbiol., 48(5), 1275-88.
- Song, Y.H., Kozarov, E.V., Walters, S.M., Cao, S.L., Handfield, M., Hillman, J.D., & Progulske-Fox, A. (2002). Genes of periodontopathogens expressed during human disease. Ann Periodontol., 7(1), 38-42.
- Dorn, B.R., Harris, L.J., Wujick, C.T., Vertucci, F.J., & Progulske-Fox, A. (2002). Invasion of vascular cells in vitro by Porphyromonas endodontalis. Int Endod J., 35(4), 366-71.
- Wu, Y., Lee, S.W., Hillman, J.D., & Progulske-Fox, A. (2002). Identification and testing of Porphyromonas gingivalis virulence genes with a pPGIVET system. Infect Immun., 70(2), 928-37.