David Nelson, Ph.D.
Summary of the focus of the research of Dr. Nelson
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 human chlamydial disease. More recently, we began studying interactions of chlamydia with the urogenital and GI microbiotas. We are especially interested in how dysbiosis in these communities impact risk and progression of a variety of common, yet idiopathic, urogenital and gastrointestinal syndromes.
Description and summary of your laboratory's research focus
Specific projects currently active in my laboratory 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 these ideas. Genetic screens are also being employed to identify genes these pathogens 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 that colonize the urogenital and GI tracts 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 sexually transmitted disease.
- Nelson DE, Virok DP, Wood H, Roshick C, Johnson RM, Whitmire WM, Crane DD, Steele-Mortimer O, Kari L, McClarty G and HD Caldwell. 2005. Chlamydial Interferon Gamma Immune Evasion is Linked to Host Infection Tropism. Proceedings of the National Academy of Science. 102(30):10658-63. http://www.ncbi.nlm.nih.gov/pubmed/16020528
Nelson DE, Crane DD, Taylor LD, Dorward DW, Goheen MM and HD Caldwell. 2006. Inhibition of Chlamydiae by primary alcohols correlates with the strain-specific complement of plasticity zone phospholipase D genes. Infection and Immunity. 74(1):73-80. http://www.ncbi.nlm.nih.gov/pubmed/16368959
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(9):2289-98. http://www.ncbi.nlm.nih.gov/pubmed/17501981
McClarty G, Caldwell HD and DE Nelson. 2007. Chlamydial interferon gamma immune evasion influences infection tropism. Current Opinion Microbiology.10:1-5. http://www.ncbi.nlm.nih.gov/pubmed/17208039
Liu X, Afrane ME, Zhong G, Clemmer DE and DE Nelson. 2010. Identification of chlamydial COMC proteins using differential proteomics. Journal of Bacteriology.192(11):2852-60. http://www.ncbi.nlm.nih.gov/pubmed/20348250
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. http://www.ncbi.nlm.nih.gov/pubmed/20351143
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. Generation of targeted Chlamydia trachomatis null mutants. Proceedings of the National Academy of Science. 108(17):7189-93. http://www.ncbi.nlm.nih.gov/pubmed/21482792
Nelson DE, Van Der Pol B, Dong Q, Revanna KV, Fan B, Easwaran S, Sodergren E, Weinstock GM, Diao L, Fortenberry JD. 2010. Characteristic male urine microbiomes associate with asymptomatic sexually transmitted infection. PLoS One. 5(11):e14116.21. http://www.ncbi.nlm.nih.gov/pubmed/21124791
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. http://www.ncbi.nlm.nih.gov/pubmed/21603636
Nelson DE, Dong QF, Van Der Pol B, Toh E, Fan B, Katz B, Mi D, Katz B, Sodergren E, Weinstock GM and Fortenberry JD. 2012. Bacterial communities of the distal urethra and coronal sulcus of adolescent males. PLos One. 7(5):e36298. http://www.ncbi.nlm.nih.gov/pubmed/22606251
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
Assistant Professor 2006-2012 Indiana University, Bloomington