Deborah Dean

Research Interests

My laboratory team is deciphering chlamydial disease pathogenesis using molecular biology, tissue modeling and engineering, nanotechnology, functional genomics and bioinformatics. Much of what we learn is being applied to drug discovery and vaccine development.

Research Summary

Tissue modeling and engineering: We are in the process of using primary human endometrial cell biopsies to develop an ex vivo glandular explant system to study the immunopathogenesis of C. trachomatis infections, which will more closely mirror what happens in vivo compared to knowledge that has been gained using only the mouse model of genital tract infections. Our studies may lead to novel data for rational vaccine development. In addition, we are interested in developing a synthetic tissue system for the same purposes. This model system will be extended to our studies of C. pneumoniae pulmonary infections.

Nanotechnology: We have been using SERS particles tagged with monoclonal antibodies (MAbs) to determine the efficacy of each in detecting immune mediators and infectious pathogens in human tissue. Eventually, we hope to be able to use SERS tagged particles to quantitate each immune mediator and pathogen via multiplexing of the particles in tissue sections. By combining novel nanotechnology with measures of humoral and cell mediated immune responses for different C. trachomatis infection and disease states, we will have a more complete understanding of the immunopathogenesis of these diseases that will aid in developing treatment strategies and an efficacious vaccine.

Functional genomics and Bioniformatics: We have a large ongoing research project to genome sequence multiple reference strains and recent clinical isolates of C. trachomatis from human populations and perform comparative genomics and function genomics based on our findings. These data will likely provide invaluable information about strain evolution, emergence of new strains and genes of interest for functional studies and vaccine design. Some of the questions we are addressing include:

1) What genetic determinants are linked to tissue tropism, virulence, disease outcome and persistence?

2) Is the evidence for intra-species genetic exchange, as observed in our recent analysis of ompA and omcB for C. trachomatis, C. pneumoniae, and C. psittaci, linked to shifts in tissue tropism or pathogenicity for C. trachomatis? 3) Is C. trachomatis acquiring virulence genes from other chlamydial species?

4) Does genetic differentiation of reference strains and clinical strains from different time points suggest the mechanism of evolution of this pathogen and predict strain types that will arise over time?

Selected Publications

Dean D, Suchland R, and Stamm W. Apparent long-term persistence of Chlamydia trachomatis cervical infections - analysis by omp1 genotyping. J Infect Dis 2000; 182:909-16.

Millman K, Black CM, Johnson R, Stamm WE, Jones R, Hook E, Martin D, Bolan G, Tavaré S, and Dean D. Population-based Genetic and Evolutionary Analysis of Chlamydia trachomatis Urogenital Strain Variation in the United States. J Bacteriol 2004;186:2457-65.

Johnston SC, Zhang H, Messina LM, Lawton MT and Dean D. Burden of Chlamydia pneumoniae Infection in Carotid Arteries is Associated with Up Regulation of Plaque IL-6 and Elevated Serum Levels of C-Reactive Protein. Arterioscler, Thromb Vasc Biol 2005;25:2648-53.

Atik B, Thanh TTK, Luong VQ , Lagree S, and Dean D. Impact of Annual Targeted Treatment on Infectious Trachoma and Susceptibility to Reinfection. JAMA 2006; 296:1488-97.

Gomes JP, Bruno WJ, Nunes A, Santos N, Florindo C, Borrego MJ, and Dean D. Evolution of Chlamydia trachomatis Diversity Occurs by Widespread Interstrain Recombination Involving Hotspots. Genome Research 2006; Nov. 7 Online in advance of print.