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Research at Darville Lab

Faculty and Lab Members

The research lab of Toni Darville, MD has studied the pathogenesis of genital tract disease due to Chlamydia trachomatis for many years. Using mouse, guinea pig, and macaque models of chlamydial infection, Dr. Darville’s research team has discovered immune signaling pathways active in disease development. They determined a role for the innate immune receptor, TLR2, in induction of pathology, and that neutrophils and IL-1 signaling pathways are key players in disease development. The Darville lab continues to pursue studies that explore host-pathogen interactions responsible for induction of disease. Her lab is using plasmid-deficient attenuated chlamydial strains that do not induce pathology but lead to induction of protective adaptive immune responses, as tools for separating pathogen-specific virulence factors from pathogen-host interactions that drive protection. The development of a chlamydial antigen-specific TCR transgenic mouse has proved to be a valuable tool to advance investigations of the adaptive T cell response to chlamydial infection with the ultimate goal to determine mechanisms to induce protective T cell memory. You can read more about her work in the lab throughout the rest of this site.
Avinash is a Research Assistant Professor with international experience in developing mucosal vaccines in Chlamydia and Herpes. As part of his PhD studies at Queensland University of Technology, his work led to the development of recombinant Chlamydia pecorum vaccine in koalas (PMID: 2408637924012135233063722223058321496349). During his 1.5 years of post-doctoral training at Queensland University of Technology, he was involved in several projects that led to testing various adjuvant formulations for a promising recombinant Chlamydia vaccine (PMID: 28602608), development of a novel vaccine strategy that demonstrated sterilizing immunity (PMID: 26647717) and established a male mouse model to study the impact of chlamydia in males (manuscripts under progress). Currently, he is working on identifying the immunological correlates of natural immunity in women infected with Chlamydia trachomatis (PMID: 32214192) and also contributes to several other projects (PMID: 29363185, 32601108, 33087404). He has hands-on experience in:

  • Flow cytometry. He has established several 12 – 15 color panels for phenotyping as well as intracellular staining
  • Mass cytometry (CyTOF). He has established a 34 marker phenotype panel for PBMCs (AAI 2018 presentation abstract) and human genital tract tissues as well as 37 marker ICS panel for PBMCs.
  • High-dimensional data analysis (viSNE, CITRUS)
  • Confocal microscopy
Catherine O’Connell’s interest in bacterial pathogenesis stems from early training in Staphylococcus aureus genetics, evolving through her study of the intracellular pathogen Shigella flexneri, to her current research interest, the obligate intracellular pathogen Chlamydia trachomatis.

Dr. O’Connell’s principal research goals are directed towards understanding the virulence mechanisms used by chlamydial species to cause disease. She has a strong interest in the complex host-pathogen interactions involved in chlamydial infection, particularly those influenced by the presence of the conserved resident plasmid. In addition, she is also interested in chlamydial-cell interactions that influence the flow of important metabolic intermediates to inclusion-bound microorganisms or that result in host-directed modification of chlamydial proteins that ultimately may alter immune-recognition and antigen presentation.

Dr. O’Connell has developed a recent interest in investigating the impact of chlamydial infection on human inflammatory responses using transcriptional profiling and in studying the genomics of chlamydial strains associated with pelvic inflammatory disease, the most damaging manifestation of genital tract infection caused by C. trachomatis. The goal of this research is to identify biomarkers, both host and bacterial, that can predict risk for severe reproductive tract morbidities such as infertility and ectopic pregnancy.

Dr. Zheng’s research focuses on:

  • Translational research to identify disease biomarkers through combined analysis of multi-omics data, including mRNA, miRNA, and DNA.
  • Identification of the disease susceptibility genes and their regulatory network in infectious diseases for pathogenesis and improved prevention and treatment.
  • Development of statistical algorithms for mediation analysis, causal network analysis and statistical deconvolution.
Christine is a current first year nursing student in UNC’s School of Nursing. Christine focuses on bacterial genetic cloning, PCR, and DNA isolations to better understand the host-pathogen interaction in chlamydial infections. She has recently been studying the influence of chlamydial plasmids on cell metabolism and immune recognition.
Jenna is a Research Specialist in the Darville Lab. Her research interests include interactions between Chlamydia and the host, host innate immune response and other protection mechanisms.
Morgan is interested in host-pathogen interactions and the mechanisms that affect chlamydial virulence. She is currently profiling the responses of glgA and omcA to environmental stresses to better understand chlamydial virulence gene expression.
Chuwen got his undergraduate degree in Pure and Applied Mathematics from Tsinghua University, Beijing, China. He is currently a second year Ph.D. student in Biostatistics. He mainly focuses on single cell RNA sequencing data analysis and gene set testing. His research interest is developing statistical and machine learning methods for data analysis in biomedical studies.
Yutong is a Ph.D. candidate in the Department of Biostatistics and received her undergraduate degree from Beihang University. She primarily carries out statistical analyses on experimental data collected by the lab and provides biomedical interpretations of analysis results. Her research interest is in developing novel statistical methods for high-dimensional data analysis and data integration problems that emerge in biomedical studies.
Bryan utilizes mouse models and a primary human fallopian tube epithelial culture to determine the mechanisms that induce excessive neutrophil influx and epithelial transmigration that results in irreversible damage to the upper genital tract during chlamydial infections.
Sam is studying the regulation of omcA and glgA in C. trachomatis L2 and C. muridarum, to determine their regulation and kinetics under conditions of stress. I am primarily interested in the genomics and genetic regulation of chlamydia, virulence mechanisms used by chlamydial species to cause disease, and host-pathogen interactions facilitated by elements conserved in the chlamydial plasmid. I utilized high throughput RNA sequencing, chlamydial culture and transformation, as well as classical genetic analyses utilizing E. coli to better understand mechanisms of virulence and immune response.
Dr. Poston’s research interests include the study of protective innate and adaptive immune responses against Chlamydia. Taylor is currently utilizing a TCR transgenic mouse to study CD4 T cell activation, memory, differentiation, and migration during intravaginal Chlamydia muridarum.
Breanna received a B.S. in microbiology from the University of Minnesota-Twin Cities. Breanna is interested in host-pathogen interactions and how these interactions can influence pathogenesis and disease. Her current research focuses on determining how the chlamydial virulence factor, Pgp3, interacts with host cell proteins and other chlamydial proteins to cause inflammation and disease during Chlamydia infection.
Dr. Wyrick’s academic career began as Chlamydia trachomatis was just being recognized as a sexually transmitted diseases pathogen. She developed the first in vitro polarized human genital epithelial cell model system that revealed:

  • Chlamydial entry via clathrin-coated pits
  • Greater entry and infectivity in estrogen- vs progesterone-dominant epithelia
  • Exit of serovar E EB progeny to the apical epithelial surface for ascension canalicularly to the upper genital tract vs basal release of invasive serovar LGV to the submucosa for infiltration of lymph nodes
  • Importance of analyzing chlamydial antibiotic efficacy in the polarized epithelial orientation
  • Polymorphonuclear leukocytes loaded with azithromycin could migrate from the basal polarized monolayer to deliver the antibiotic in bioreactive form to chlamydiae in apical inclusions.

Dr. Wyrick’s current activities include assistance with chlamydial infection of polarized fallopian tube epithelia and electron microscopy analyses of chlamydial infection in secretory and/or ciliated epithelial cells.

Alumni

Clare joined the Darville Lab in 2016 and was co-mentored by Drs. Darville and Nagarajan. During her PhD, Clare used mouse models to study the immune signals that bring in immune cells (particularly neutrophils) during and after infection, and how those signals contribute to wound healing, leading to long-term scarring of the oviduct. Clare defended her thesis, “The role of Interleukin-1 alpha and the noncanonical inflammasome in murine chlamydial oviduct disease,” in June 2020.