Caroline Attardo Genco, Ph.D.

Caroline A. 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 has been the leading investigator in defining the regulation of genes involved in iron transport and virulence by the transcriptional regulator protein Fur, in Neisseria pathogenesis. Her recent studies have identified several novel gonococcal genes, which are under iron and Fur control. Furthermore, she has determined that a subset of these Fur regulated gonococcal genes are expressed during mucosal Neisseria gonorrhoeae infection in both men and women. In collaboration with investigators at Chiron Vaccines in Sienna, she has also utilized DNA microarray and computational-directed analysis to identify novel Fur-dependent genes in the mucosal pathogen Neisseria meningitides. Of special interest is her discovery of the regulation of a major surface protein, which is a vaccine candidate for N. meningitides by iron and Fur.

Dr. Genco together with collaborators at Harvard Medical has characterized the proinflammatory response to N. gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells. She has shown that gonococci stimulate distinct proinflammatory host responses in morphologically and functionally different compartments of the lower female genital tract. These are significant findings and this may contribute directly to the inflammatory signs and symptoms characteristic of disease caused by N. gonorrhoeae. Dr. Genco is currently using these tissue culture model systems to examine gonococcal gene expression profiles during active invasion of epithelial cells.

Through both genetic and biochemical approaches, Dr. Genco’s laboratory has defined the proteins required for heme and hemoglobin utilization in P. gingivalis. In addition, her laboratory has demonstrated that hemin can coordinately regulate the expression of several virulence factors. Recent studies indicate that the hemin transport system may also influence the expression of the arginine specific cysteine proteinases (gingipains) produced by P. gingivalis. The gingipains are major virulence factors and current studies in her laboratory are aimed at using these proteins as putative vaccine candidates.

Finally, an exciting area of work in Dr. Genco’s laboratory is her recent findings that oral infection with the periodontal disease pathogen P. gingivalis accelerates atherosclerotic plaque accumulation in a murine model of atherosclerosis. Infection with P. gingivalis and the biological consequences for increased risk for cardiovascular disease has recently received considerable attention. Dr. Genco has further established that P. gingivalis accelerated atherosclerotic plaque accumulation is mediated by innate immune recognition to invasive bacterial infection. Her laboratory has recently established that P. gingivalis infection and inflammation in endothelial cells is mediated through fimbriae signaling through Toll-like receptors. The ability to multiply in and to activate endothelial cells may be one of the pathogenic mechanisms exerted by P. gingivalis that may explain the observed association between this organism and coronary heart disease.

Representative Publications

  1. Simpson, W., T. Olczak, and C.A. Genco. 2000. Characterization and expression of HmuR, a TonB-dependent hemoglobin receptor of Porphyromonas gingivalis. J. Bacteriol. 182:5737-5748.
  2. Genco, C.A. and D.W. Dixon. 2001. Emerging strategies in microbial heme capture. Mol. Microbiol. 39: 1-11.
  3. Sroka, A., M. Sztukowska, J. Potempa, J. Travis, and C.A. Genco. 2001. Degradation of host heme proteins by the lysine and arginine-specific cysteine proteinases (gingipains) of Porphyromonas gingivalis. J. Bacteriol. 183:5609-5616.
  4. Olczak, T., D.W. Dixon, and C.A. Genco. 2001. Binding specificity of the Porphyromonas gingivalis heme / hemoglobin receptor HmuR and gingipain K and gingipain R for heme, porphyrins, and metalloporphyrins. J. Bacteriol. 183:5599-5608.
  5. Fichorova, R.N., P. Desai, F. Gibson, and C.A. Genco. 2001. Distinct proinflammatory host responses to Neisseria gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells. Infect. Immun. 69:5840-5848.
  6. Sebastain, S., J. Murphy, S. Agarwal, and C.A. Genco. 2002. The gonococcal Fur regulon: Identification of additional genes involved in major catabolic, recombination and secretory pathways. J. Bacteriol. 184: 3965-3974.
  7. Grifantini, R., S. Sebastian, E. Frigimelica, M. Draghi, E. Bartolini, A. Muzzi, R. Rappuoli, G. Grandi, and C.A. Genco. 2003. Identification of novel iron-activated and repressed Fur-dependent genes by transcriptome analysis of Neisseria meningitides Group B. Proc. Natl. Acad. Sci. USA 100:9542-9547.
  8. Gibson, F.C., Hong, C., Chou, H.H., Yumoto, H., Chen, J., Lien, E., Wong, J. and C.A. Genco. 2004. Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation. 109:2801-2806.
  9. Genco, C.A. and F.C. Gibson, III. 2004. Infection and Atherogenesis. In: Molecular mechanisms in atherosclerosis. J. Loscalzo, Editor. pg.237-260.
  10. Grifantini, R., E. Frigimelica, E. Delany, E. Bartolini, S. Balloni, S. Agarwal, C.A. Genco, and G. Grandi. 2004. Characterization of a novel Neisseria meningitides Fur and iron-regulated operon required for protection from oxidative stress: Gene function assignment by DNA microarray. Mol. Microbiol. 54:962-979.
  11. Sztukowska, M., A. Sroka, M.M. Bugno, A. Banbula, Y. Takahashi, C.A. Genco, J. Travis and J. Potempa. 2004. The C-terminal domains of the gingipain K polyprotein are necessary for assembly of the active enzyme and expression of associated activities. Mol. Microbiol. 54:1393-1408.
  12. Liu, X., A. Sroka, J. Potempa, and C.A. Genco. 2004. Coordinate expression of the Porphyromonas gingivalis lysine-specific gingipain protease, Kgp, arginine-specific gingipain proteinase, RgpA, and the heme / hemoglobin receptor, HmuR. Biol. Chem. 385:1049-1057.
  13. Chou, H-H., H. Yumoto, M. Davy, Y. Takahashi, T. Miyamoto, F.C. Gibson and C.A. Genco. 2005. Porphyromonas gingivalis fimbria-dependent activation of inflammatory genes in human aortic endothelial cells. Infect. Immun. 73: 5367-5378.
  14. Agarwal, S., C. King, E. Klein, D.E. Soper, P.A. Rice, L.M. Wetzler, and C.A. Genco. 2005. The gonococcal Fur-regulated tbpA and tbpB genes are expressed during natural mucosal gonococcal infection. Infect. Immun. 73:4281-4287.
  15. Yumoto, H., H.H. Chou, Y. Yakahashi, M. Davey, F.C. Gibson, and C.A. Genco. 2005. Sensitization of human aortic endothelial cells to lipopolysaccharide via regulation of Toll-like receptor 4 by bacterial fimbria-dependent invasion. Infect. Immun. 73:8050-8059.
  16. 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(2):1376-1380.
  17. Liu, X., T. Olczak, H.C. Guo, D. Dixon, and C.A. Genco. 2006. Identification of essential amino acid residues required for hemoprotein utilization in the Porphyromonas gingivalis heme receptor HmuR. Infect. Immun. 74(2):1222-1232.
  18. Takahashi, Y., M. Davey, H. Yumoto, 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. In Press

 

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Primary teaching affiliate
of BU School of Medicine