Caroline Genco Associate Professor caroline.genco@bmc.org

education

MS, Ph.D, University of Rochester, School of Medicine and Dentistry

research goals

Dr. Genco’s laboratory is interested in the characterization of specific bacterial virulence factors produced by the mucosal pathogens Neisseria gonorrhoeae and Porphyromonas gingivalis, and the underlying molecular mechanisms by which these factors enable these organisms to cause disease. She is particularly interested in mechanisms utilized for colonization and in particular in the ability of environmental factors to modulate bacterial gene expression. Her laboratory has defined the mechanisms of iron transport in both N. gonorrhoeae and P. gingivalis, characterized several outer membrane receptors required for transport and utilization of iron from heme and hemoglobin, and defined the role of the energy transducing protein in this process. Dr. Genco’s laboratory is also particularly interested in how virulence genes are expressed in vivo and particular 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. A Fur homolog has been identified in N. gonorrhoeae and in P. gingivalis and new data from Dr. Genco’s laboratory has defined the Fur-regulon in both these pathogens. These initial studies have established that the transcriptional regulatory protein Fur controls the expression of numerous genes that are required for the virulence of N. gonorrhoeae and P. gingivalis. 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 expressing GFP (green fluorescent protein) 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. Work with P. gingivalis has focused on the interactions of P. gingivalis with endothelial cells. P. gingivalis infection has recently been associated with chronic inflammatory diseases such as atherosclerosis. Recognizing that the strength of the epidemiological associations of P. gingivalis with atherosclerosis can be increased by the demonstration that P. gingivalis can initiate and sustain growth in human vascular cells, her laboratory has characterized the response of the endothelial cell to this pathogen. Her laboratory has demonstrated that P. gingivalis and outer membrane components can induce the expression of chemokines and surface associated cell adhesion molecules. Stimulation of adhesion molecules involved in the recruitment of leukocytes to sites of inflammation by P. gingivalis may play a role in the pathogenesis of systemic diseases associated with this microorganism, including atherosclerosis.

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 the P. gingivalis cysteine proteases (gingipains), major virulence factors of this organism, function in a protective manner in animal models following P. gingivalis challenge. Current work is focused on expression of these antigens for the induction of a more robust mucosal response through the use of Salmonella avirulent vectors

recent publications

Simpson, W, Sroka, A., Potempa, J., Travis, J. and Genco, CA. Characterization and expression of HmuR, a TonB-dependent hemoglobin receptor of Porphyromonas gingivalis. J. Bacteriol. 182: 5737-5748, 2000.

Desai, P., Garges, IE. and Genco, CA. Pathogenic Neisseria can use hemoglobin, transferrin, and lactoferrin independently of the tonB locus. J. Bacteriol. 182: 5586-5591, 2000.

Graves, D., Jiang Y. and Genco CA. Periodontal Disease: Bacterial virulence factors, host response and impact on systemic health. Curr.Opin. Infect. Dis. 13:227-232, 2000.

Forng, RY., Champagne, C., Simpson, W. and Genco CA. Environmental cues and gene expression in Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. Oral Diseases: 6: 351-365

recent grants

Hemin utilization by Porphyromonas gingivalis,3/15/91-3/14/0, NIDR-RO1

“Use of P. gingivalis gingipain R1 peptides for oral immunization”,4/99 - 3/03, NIDR-R01

Modulation of Molecular Pathogenesis in Systemic Diseases, 4/00-3/04, NIDR-P01

E-selectin		P-selectin
uninfected	infected	uninfected	infected
Confocal microscopy demonstrating that P. gingivalis infection of endothelial cells induces the expression of E and P-selectin.