Faculty & Research
- Contact Information
- Contact David Nelson by nelsonde [at] indiana [dot] edu
- By telephone: 812-856-2813/5-3145(lab)
- MS 420
Ph.D., 2001 University of North Dakota School of Medicine
Postdoctoral Fellow 2001-2002 IUPUI, Indianapolis
Postdoctoral Fellow 2002-2006 Rocky Mountain Labs, NIH/NIAID
2009 Trustees Teaching Award
Chlamydial pathogenesis and pathogen discovery
Chlamydiae are obligatory parasites that live inside eukaryotic cells. Multiple species are pathogens and cause disease in humans. Short-term goals of our research are to identify and characterize virulence factors that dictate chlamydial tropism. Long term, we will apply these findings toward vaccine design and improving animal models of chlamydial disease. More recently, we began studying interactions of chlamydia with other bacteria and the possible contributions of these bacteria to idiopathic reproductive tract syndromes.
Specific projects include:
1. Characterization of chlamydial pathogenicity factors: The genomes of C. trachomatis strains that cause distinct disease can share more than 99% sequence identity. Much of the genetic variation among these strains maps to a short region of their genomes termed the plasticity zone (PZ). Two strain-variable PZ gene families, the chlamydial cytotoxins and phospholipase D homologs, share homology with virulence factors of other pathogens. We are attempting to identify the functions of these genes using bacterial genetics, proteomics and animal modeling.
2. Development of genetic approaches for analysis of chlamydial-host: interactions: Most chlamydial genes are highly conserved, even in pathogenically distinct species. These core genes mediate shared aspects of chlamydial intracellular biology. In contrast, PZ genes are more variable and may dictate chlamydial niche specificity. We are using mutagenesis and TILLING (see Kari et al. 2011) to isolate PZ mutants and test this ideas. Genetic screens are also being employed to identify genes chlamydiae use to target different tissues and circumvent immunity.
3. Microbiome of the human urogenital tract and pathogen discovery: The male urogenital tract has classically been viewed as sterile. Results from our group challenge this idea and suggest that uncharacterized microorganisms colonize the urogenital tract and may be relevant to diseases of known (such as Chlamydia) and unknown etiologies (Nelson et al., 2010). We are using state-of-the-art sequencing approaches to characterize urogenital microorganisms in adolescents and in men at high risk for sexually transmitted disease. Our long-term goals are to identify and study uncharacterized microorganisms relevant to reproductive tract disease.
- Kari L, Goheen MM, Randall LB, Taylor LD, Carlson JH, Whitmire WM, Virok D, Rajaram K, Endresz V, McClarty G, Nelson DE, Caldwell HD. 2011. Targeted generation of null mutations in Chlamydia trachomatis genes. PNAS. 108(17):7189-93.
Dong Q, Nelson DE, Toh E, Diao L, Gao X, Fortenberry JD, Van der Pol B. 2011. The microbial communities in male first catch urine are highly similar to those in paired urethral swab specimens. PLoS One. 6(5):e19709.
- Taylor LD, Nelson DE, Whitmire B and HD Caldwell. 2010. Characterization of the Chlamydia trachomatis Mac Perforin Homolog CT153. Infection and Immunity. 78(6):2691-9.
- Nelson DE, Van Der Pol B, Dong Q, Revanna KV, Fan B, et al. 2010. Characteristic Male Urine Microbiomes Associate with Asymptomatic Sexually Transmitted Infection. PLoS ONE 5(11): e14116.
- Burian K, Endresz V, Deak J, Kormanyos S, Nelson DE and DP Virok. 2010. Transcriptome analysis indicates an enhanced activation of adaptive and innate immunity by Chlamydia infected and IFN-g treated murine epithelial cells. J. Infectious Disease. 202(9):1405-14.
- Liu X, Afrane ME, Zhong G, Clemmer DE and DE Nelson. 2010. Identification of chlamydial COMC proteins using differential proteomics. J. Bacteriology. 192(11):2852-60.
- Kari L, Whitmire WM, Carlson JH, Crane DD, Reveneau N, Nelson DE, Mabey DC, Bailey RL, Holland MJ, McClarty G and HD Caldwell. 2008. Pathogenic diversity among Chlamydia trachomatis ocular strains in non human primates is affected by subtle genomic variations. J. Infectious Disease. 197(3):449-56.
- Raff EC, Schollaert KL, Nelson DE, Donoghue PC, Thomas CW, Turner FR, Stein BD, Dong X, Bengtson S, Huldtgren T, Stampanoni M, Chongyu Y and RA RAff. 2008. Embryo fossilization is a biological process mediated by microbial biofilms. PNAS. 105(49):19360-5.
- McClarty G, Caldwell HD and DE Nelson. 2007. Chlamydial interferon gamma immune evasion influences infection tropism. Current Opinion Microbiology.10:1-5.
- Nelson DE, Taylor LD, Shannon, JG, Whitmire WM, Crane DD, McClarty G, Su H, Kari L and HD Caldwell. 2007. Phenotypic rescue of Chlamydia trachomatis growth in IFN-g treated mouse cells by irradiated Chlamydia muridarum. Cellular Microbiology. 9:2289-98.