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Faculty and Lab Members
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. 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.
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.
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.
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: 24086379, 24012135, 23306372, 22230583, 21496349). 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: 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
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.
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.
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.
- 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.