Role of Immunogenetic Determinants on Human Genital Chlamydial Infection

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DESCRIPTION (provided by applicant): Dr. Geisler is an Assistant Professor of Medicine in the Division of Infectious Diseases at the University of Alabama at Birmingham. His goal is to become an independent translational researcher and leader in the area of chlamydia immunogenetics. Despite efficacious treatments, sensitive tests, screening programs, and educational interventions, genital chlamydia remains highly prevalent worldwide and causes significant morbidity. Dr. Geisler hopes to aid in chlamydia prevention and control by applying translational research efforts to better understand human immune responses to chlamydia and to contribute knowledge needed for vaccine development. He has identified two individuals, Dr. Richard Kaslow, a recognized leader in STD genetics research, and Dr. Richard Morrison, an accomplished researcher in chlamydia immunology, as his co-mentors. The proposed career development plan will provide Dr. Geisler with comprehensive hands-on laboratory training in skills necessary to conduct chlamydia immunogenetics research, as well as allow him to supplement his already completed MPH in Epidemiology with further advanced (PhD level) didactic training in epidemiology, biostatistics, immunology, genetics, and clinical research conduct. The primary study objective is to examine the influence of human genetic determinants (HLA variants and cytokine genotypes) on clinical outcomes and protective immunity in chlamydia, and Dr. Geisler will test the hypothesis that specific human genetic determinants influence chlamydial eradication (in a subgroup of asymptomatic patients returning for therapy for a positive chlamydia test), and resistance (i.e. protective immunity) to recurrent chlamydia. The study will be conducted in a cohort of up to 380 male and female STD clinic patients with genital chlamydia, categorized into 3 groups based on differences in the clinical presentation prior to therapy, who all will return for repeat chlamydial testing and immunogenetic testing in 6 months post-therapy. Preliminary data from retrospective analyses performed on a different cohort revealed HLA-DQB1*06 and interleukin-10 cytokine gene polymorphisms were associated with recurrent chlamydia. Accordingly, a second research objective will be to define how genetic determinants modulate cytokine expression. The proposed training and research will help Dr. Geisler become an independent translational researcher. Study findings will aid in study design and hypothesis generation for a future R01.