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Research at Darville Lab

Faculty and Lab Members

Dr. Darville’s lab has successfully used 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.

Her team’s research is using human blood and genital tract tissue samples collected from women at high risk and followed longitudinally to determine chlamydial proteins that induce protective CD4 T cell responses. She is examining the role of antigen-specific T cells and antibody in protection from ascending infection and from reinfection. She is examining the contributory roles of Th17 cells and T regulatory cells in immunopathogenesis and protection using human samples and mouse models. The development of a chlamydial antigen-specific TCR transgenic mouse model provides an excellent 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.

Her lab is seeking to identify the local inflammatory and fibrotic pathways most strongly regulated during Chlamydia trachomatis infection utilizing specimens obtained from women with chlamydial pelvic inflammatory disease and women with asymptomatic chlamydial infection. They are also working to identify biomarkers for susceptibility to Chlamydia trachomatis infection.

Dr. Duncan’s research contributions include serving as the liaison between the lab  and the Pathology Services Core with many ongoing mouse experiments, focusing on the development of a spatial multi-plex imaging system to pursue an understanding of the immune cell-based mucosal response to Chlamydia, and taking charge of all logistics for the Pfizer vaccine program.
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. Poston is a chlamydiologist and T cell immunologist interested in translational immunology and vaccinology. His current research is focused on defining protective immune correlates and determining adjuvants and immunization strategies to enhance genital tract immunity. The current objective of his research is to better understand how CD4 T cells mediate protection against chlamydial infection and how to design efficacious vaccines. He is currently utilizing a TCR transgenic mouse model (TP-1 mice) to interrogate CD4 T cell responses during infection, and directing pre-clinical vaccine studies using viral vector, mRNA, and recombinant protein vaccine platforms in collaboration with academic and industry partners. This research has generated first-generation subunit vaccines that contain a novel Stimulator of Interferon Genes (STING) agonist that can be covalently attached to Chlamydia antigens for immunization. This vaccine platform is undergoing further refinements to enhance vaccine delivery and immunogenicity, while also serving as a benchmark for future testing of alternative adjuvants and vaccine constructs.
Dr. Zheng is a multidisciplinary scientist specializing in systems immunology of infectious diseases and vaccines, human genetics, and biostatistics. She has extensive experience working with large infectious disease cohorts and conducting multi-omics data analyses. Her primary interest lies in identifying protective systemic blood and local mucosal cellular immune responses against viral or bacterial infections and diseases using systems immunology methods.

Leveraging large human cohorts exposed to sexually transmitted pathogens, her team has analyzed host blood mRNA transcriptomes, determined transcriptional endotypes in women with subclinical disease, and identified a blood transcriptional biomarker for asymptomatic infected subpopulations. Recently, in collaboration with her colleagues, they identified unique T cell subset signatures associated with reduced Chlamydia reinfection in a highly exposed cohort using Cytometry by Time-Of-Flight (CyTOF) and single-cell sequencing (scRNA-seq) of blood and cervical swabs. In addition to cellular immunity, the team analyzed binding antibody responses to Chlamydia genital tract infection and determined that protein-specific binding antibodies do not correlate with protection from reinfection.

To address the challenges of multi-level omics and multi-cohort data analysis, her team has developed a series of new statistical methods. For early diagnosis, they created a novel causal network algorithm, a mixed graphic model, to determine the causal regulatory network in cross-sectional transcriptome data. To integrate multi-omics data of different types (e.g., mRNA and DNA -omics data) from multiple groups of subjects, they developed a Latent Mixed Gaussian Copula model, which simultaneously identifies common and disease-specific networks. Additionally, they developed new statistical methods for causal mediation pathway analysis in integrated DNA and mRNA -omics data. They are also developing novel algorithms for digital immune cell separation, rigorous multi-study normalization and batch effect correction, and integrative scRNA-seq and bulk RNA-seq data analysis.

Jenna is the Laboratory Research Manager for the Darville Lab. Her research interests include interactions between Chlamydia and the host, host innate immune response and other protection mechanisms.

Dr. Yount is a postdoctoral research fellow in the Darville lab. She received her PhD in Immunology from the Ohio State University where her research focused on improving vaccines against Bordetella bronchiseptica and B. pertussis by testing and evaluating immune responses to novel vaccine formulations and administration routes in mouse models.

In her current role in the Darville lab, Dr. Yount is pursuing her interests in immunology and vaccine development by investigating correlates of natural immunity to Chlamydia trachomatis infection in peripheral blood and cervical and endometrial specimens collected from a longitudinal cohort of highly-exposed women. Her overall goal is to use these findings to inform the design of effective vaccines. Dr. Yount is also pursuing computational and biostatistical methods to analyze the multi-dimensional data (flow cytometry, CyTOF, RNA-seq, etc.) generated by her studies, and she is currently supported for this work by the American Association of Immunology (AAI) Intersect Fellowship Program for Computational Scientists and Immunologists. She also supports projects testing pre-clinical vaccines against C. trachomatis by evaluating T cell immune responses by flow cytometry.

Aakash joined the Darville lab in 2022 as an undergraduate research assistant and now serves as a research technician. He earned his B.S. in Biology from the University of North Carolina at Chapel Hill in 2024. In his current role, Aakash applies his skills in cell culture, immunofluorescence light microscopy, and data analysis to support the team’s efforts in creating a robust and efficacious vaccine against Chlamydia.
Camille is a laboratory technician at the Darville Lab where she applies her recent education from UNC-Chapel Hill to advance research on host interactions with Chlamydia using mouse animal models. In her role, she conducts a variety of experiments to study the immune response to the pathogen, preparing samples, performing assays, and collecting data to contribute to the lab’s ongoing projects. Her primary interest lies in vaccine development, where she assists researchers in exploring innovative strategies to enhance immunity against Chlamydia.
Emily is a second year PhD student in the Microbiology and Immunology department. She earned a B.S in microbiology from the University of Wisconsin – Oshkosh in 2021 and then completed a postbaccalaureate research fellowship at the National Institutes of Health where she studied microbial therapeutics. Since joining the Darville lab in 2024, Emily has been researching novel antibiotics against chlamydia. She was recently awarded a T32 training grant in translational medicine, which will provide clinical experiences to learn how scientists and physicians can work together to better human health. Emily is interested in the development of novel therapeutics, the microbiome, immunological response to infection, and mouse models to study these topics.
Grace joined the Darville lab in 2023 after receiving a B.S. in Microbiology from Clemson University. At Clemson she studied protein-protein interactions in meiotic homologous recombination.  She is currently pursuing a PhD in Microbiology and Immunology. Grace is particularly interested in immunology and vaccinology. Her current research utilizes mouse models to investigate the immune requirements and vaccination strategies for protection against pathology after chlamydial challenge.

Alumni

Avinash was 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). In the Darville lab, he had been working on identifying the immunological correlates of natural immunity in women infected with Chlamydia trachomatis (PMID: 32214192) and also contributed to several other projects (PMID: 293631853260110833087404). 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

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.

Bryan utilized 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.
Christine was a first year nursing student in UNC’s School of Nursing. Christine focused on bacterial genetic cloning, PCR, and DNA isolations to better understand the host-pathogen interaction in chlamydial infections. She had been studying the influence of chlamydial plasmids on cell metabolism and immune recognition.

Chuwen got his undergraduate degree in Pure and Applied Mathematics from Tsinghua University, Beijing, China. He was a second year Ph.D. student in Biostatistics. He mainly focused 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.

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.

Morgan is interested in host-pathogen interactions and the mechanisms that affect chlamydial virulence. In the Darville lab, she was profiling the responses of glgA and omcA to environmental stresses to better understand chlamydial virulence gene expression.

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 activities in the Darville lab included assistance with chlamydial infection of polarized fallopian tube epithelia and electron microscopy analyses of chlamydial infection in secretory and/or ciliated epithelial cells.

Sam was studying the regulation of omcA and glgA in C. trachomatis L2 and C. muridarum, to determine their regulation and kinetics under conditions of stress. Sam was 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. Sam 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.
Yutong was a Ph.D. candidate in the Department of Biostatistics and received her undergraduate degree from Beihang University. She primarily carried out statistical analyses on experimental data collected by the lab and provided 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.