Caroline Attardo Genco, Ph.D.
Professor of Medicine and Microbiology and
Associate Professor in the Department of Periodontology and Oral Biology, Goldman School of Dentistry
B.S. State University of New York at Fredonia
M.S. University of Rochester, School of Medicine and Dentistry
Ph.D. University of Rochester School of Medicine and Dentistry
Dr. Genco’s laboratory is interested in the characterization of specific bacterial virulence factors produced by the mucosal pathogens Neisseria gonorrhoeae, N. meningitidis, and Porphyromonas gingivalis, and the underlying molecular mechanisms by which these factors enable these organisms to cause disease. Dr. Genco’s laboratory is particularly interested in how virulence genes are expressed in vivo and the role of iron in gene regulation in vivo. Iron starvation is used as a signal by many pathogens that they are in a host environment resulting in the expression of virulence factors that are transcriptionally regulated by iron through the ferric uptake regulator protein, Fur. Dr. Genco’s laboratory has defined the Fur-regulon in N. gonorrhoeae, N. meningitidis and in P. gingivalis. Her studies have established that the transcriptional regulatory protein Fur controls the expression of numerous genes that are required for the virulence of N. meningitidis and N. gonorrhoeae. Her laboratory as also recently identified a novel mechanism for Fur-mediated regulation through small regulatory RNAs. Current studies are aimed at examining the regulation and expression of Fur-regulated genes in vitro, and in vivo directly in clinical specimens. Several different model systems are used to examine the interactions of bacteria with the host. These include animal models for gonococcal infection and P. gingivalis oral infection. Her laboratory also utilizes epithelial and endothelial cells to study the interactions of N. gonorrhoeae and P. gingivalis with host cells, which are permissive for these pathogens. Currently the laboratory is examining the interactions of N. gonorrhoeae with endocervical, ectocervical and vaginal cell lines. Using these cell lines they have demonstrated distinct proinflammatory responses in different compartments of the female lower genital tract. Furthermore she has also utilized these cells to demonstrate that infection with N. gonorrhoeae inhibits the apoptotic response of these cells. Thus N. gonorrhoeae may establish infection in women by inhibiting the apoptotic response to infection, thereby resisting killing from both the host cell and the innate immune response. Furthermore, prolonged survival of the host cell potentially allows the bacteria to successfully invade cervical tissue, eventually transcending to the upper genital tract.
Another area of interest in Dr. Genco’s laboratory is the development of vaccine candidates to prevent P. gingivalis induced periodontal disease. Using several different animal models her laboratory has demonstrated that the P. gingivalis cysteine proteases (gingipains), major virulence factors of this organism, function in a protective manner in animal models following P. gingivalis challenge. Finally, an exciting area of new work in Dr. Genco’s laboratory is examining the specific cellular and molecular mechanisms by which infectious agents contribute to chronic inflammation and specifically the role of the innate immune response in atherosclerosis. Dr. Genco has established that P. gingivalis accelerates atherosclerotic plaque accumulation and that is mediated by innate immune recognition to invasive bacterial infection. Her laboratory has established that P. gingivalis infection and inflammation in endothelial cells is mediated through fimbriae signaling through Toll-like receptors. Her laboratory has established that TLR2 plays a critical role in the atherosclerotic inflammatory response that is independent of dietary lipids. Current studies are focused on other chronic infections such as that caused by the respiratory pathogen Chlamydia pneumoniae in well-defined models of atherosclerosis and defining the role of the innate immune response in accelerated atherosclerosis. These studies employ in vitro model systems for platelet, endothelial cells, and macrophages. The common theme of these studies is to examine the role of infection and the innate immune response in early events associated with atherosclerosis in well-defined in vitro and in vivo systems.
- Miyamoto, T., H. Yumoto, Y. Takahashi, M. Davey, F.C. Gibson, and C.A. Genco. 2006. Pathogen-accelerated atherosclerosis occurs early after exposure and can be prevented via immunization. Infect. Immun. 74: 1376-1380.
- Takahashi, Y. , M. Davey, Yumoto, H., F.C. Gibson, and C.A. Genco. 2006.Fimbria-dependent activation of pro-inflammatory molecules in Porphyromonas gingivalis infected human aortic endothelial cells. Cellular Microbiol. 8: 738-757.
- Mydel, P., Y. Takahashi, H. Yumoto, M. Sztukowska, M. Kubica, F.C. Gibson, D. Kurtz, J. Travis, C.A. Genco, and J. Potempa. 2006. Role of the host oxidative immune response and the bacterial antioxidant, rubrerythrin during anaerobic infection. Plos Pathogens. 2:712-725.
- Al-Qutub, M.N, Braham, P.H., Karimi-Naser, K., Liu, X, Genco, C.A. and R.P. Darveau. 2006. Hemin-dependent modulation of the lipidA structure of Porphyromonas gingivalis lipopolysaccharide. Infect. Immun. 74: 4474-4485.
- Mellin, J.R., S. Goswami, S. Grogan, B. Tjaden, and C.A. Genco. 2007. A novel Furand iron-regulated small RNA, NerF, is required for indirect Fur-mediated regulation of the sdhA and sdhC genes in Neisseria meningitidis. J. Bacteriol. 189: 3683-3694.
- Liu, X., T. Ukai, H. Yumoto, M. Davey, F.C. Gibson, and C.A. Genco. 2008. Toll-like receptor 2 plays a critical role in the progression of atherosclerosis that is independent of dietary lipids. Atherosclerosis. 196:146-154.
- Davey, M., X. Liu, T. Ukai, V. Jain, C. Gudino, F.C. Gibson III, D. Golenbock, A. Visintin, and C.A. Genco. 2008. Bacterial fimbriae stimulate proinflammatory activation in the endothelium through distinct TLRs. J. Immunol. 180: 2187-2195.
- Ukai, T., H. Yumoto, T. Miyamoto, F.C. Gibson III, and C.A. Genco. 2008. Macrophage-elicited osteoclastogenesis in response to bacterial stimulation requires Toll-like receptor 2 dependent tumor necrosis factor-lpha production. Infect. Immun. 76: 812-819.
- Agarwal, S., S. Sebastian, B. Szmigielski, P. A. Rice, and C. A. Genco. 2008. Expression of the gonococcal global regulatory Fur, and genes encompassing the Fur and iron regulon during in vitro and in vivo infection in women. J. Bacteriol. 190:3129-3139.
- Blair, P.S, S. Rex, O. Vitseva, L. Beaulieu, K. Tanriverdi, S. Chakrabarti, C. Hayashi, C.A. Genco, M. Iafrati, and J.E. Freedman. 2009. Stimulation of Toll-like receptor 2 in human platelets induces a thrombo-inflammatory response through activation of phosphoinositide 3-kinase. Cir. Res. 104: In press.