Role of Immunogenetic Determinants on Human Genital Chlamydial Infection

描述（由申请人提供）：Geisler博士是伯明翰亚拉巴马大学传染病系的医学助理教授。他的目标是成为衣原体免疫遗传学领域的独立翻译研究人员和领导者。尽管有有效的治疗、敏感性测试、筛查计划和教育干预，生殖器衣原体在世界范围内仍然高度流行，并导致显著的发病率。Geisler博士希望通过应用转化研究工作来帮助衣原体预防和控制，以更好地了解人类对衣原体的免疫反应，并为疫苗开发提供所需的知识。他已经确定了两个人，理查德Kaslow博士，在性病遗传学研究的公认领导者，和理查德莫里森博士，在衣原体免疫学的成就研究员，作为他的共同导师。拟议的职业发展计划将为Geisler博士提供进行衣原体免疫遗传学研究所需技能的全面动手实验室培训，并允许他补充他已经完成的流行病学硕士学位，并进一步进行流行病学，生物统计学，免疫学，遗传学和临床研究行为的教学培训。主要研究目的是检查人类遗传决定因素（HLA变体和细胞因子基因型）对衣原体临床结局和保护性免疫的影响，Geisler博士将检验特定人类遗传决定因素影响衣原体根除（在衣原体检测阳性的无症状患者返回治疗的亚组中）和对复发性衣原体的抗性（即保护性免疫）的假设。该研究将在多达380名患有生殖器衣原体的男性和女性STD门诊患者的队列中进行，根据治疗前临床表现的差异分为3组，所有患者都将在治疗后6个月内返回接受重复衣原体检测和免疫遗传学检测。对不同队列进行回顾性分析的初步数据显示，HLA-DQB 1 *06和白细胞介素-10细胞因子基因多态性与衣原体复发相关。因此，第二个研究目标将是确定遗传决定因素如何调节细胞因子的表达。拟议的培训和研究将帮助Geisler博士成为一名独立的翻译研究人员。研究结果将有助于未来R 01的研究设计和假设生成。

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.