Role of Immunogenetic Determinants on Human Genital Chlamydial Infection

描述(由申请人提供)：盖斯勒博士是阿拉巴马大学伯明翰分校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员和领导者。尽管进行了有效的治疗、敏感的检测、筛查计划和教育干预，但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。盖斯勒博士希望通过应用转化研究来帮助预防和控制衣原体，以便更好地了解人类对衣原体的免疫反应，并提供疫苗开发所需的知识。他已经确定了两个人作为他的共同导师，理查德·卡斯洛博士是公认的性病遗传学研究的领导者，理查德·莫里森博士是衣原体免疫学方面的资深研究员。拟议的职业发展计划将为盖斯勒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，并允许他在完成流行病学公共卫生硕士学位的基础上，接受流行病学、生物统计学、免疫学、遗传学和临床研究指导方面的进一步高级(博士水平)教学培训。该研究的主要目标是检验人类遗传决定因素(人类白细胞抗原变异体和细胞因子基因型别)对衣原体感染的临床结局和保护性免疫的影响，盖斯勒博士将检验这样一种假设，即特定的人类遗传决定因素影响衣原体根除(衣原体检测呈阳性而返回治疗的无症状患者的子组)和对复发衣原体的抵抗力(即保护性免疫)。这项研究将在多达380名男性和女性性病门诊生殖器衣原体患者中进行，根据治疗前临床表现的不同分为3组，这些患者都将在治疗后6个月内返回进行重复的衣原体检测和免疫遗传检测。对不同队列进行的回顾性分析的初步数据显示，人类白细胞抗原-DQB1*06和白细胞介素10细胞因子基因多态与复发性衣原体有关。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。拟议中的培训和研究将帮助盖斯勒博士成为一名独立的翻译研究员。研究结果将有助于未来R01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.