Immunogenetic Determinants of Chlamydia Reinfection and Chlamydia-Associated Infertility in Women

项目摘要/摘要 此NIH F31-分集应用程序的目的是获得对PI、Kristin Olson、 在她的医学/博士学位培训中指导研究和职业发展活动，这将增强她的能力 有可能成为一名成功的内科科学家。该项目的目标是发展统计遗传学的技能。 这将允许PI研究免疫遗传决定因素对沙眼衣原体(CT)的影响。 妇女感染结果，包括遗传数据质量控制、归因、多重检测等方法 修正和路径分析。研究建议的主要目标是调查 女性沙眼衣原体再感染和沙眼衣原体相关性不孕的免疫遗传决定因素。 CT感染是全世界最流行的性传播细菌感染，包括在美国 由于其引起的生殖疾病，对妇女的影响不成比例。高达20%的女性经历过 治疗后的再感染和反复感染CT的炎症可能会增加CT感染的风险。 伴发不孕症。目前尚不清楚为什么一些女性在接受治疗后仍然容易感染CT，导致 再次感染，以及为什么一些CT感染会导致不孕。该项目寻求确定遗传风险标记 CT再感染和CT相关不孕症(目标1A和2A)，然后利用复杂的统计方法 预测这些遗传标记(目标1B和2B)介导的免疫反应。中心假设是 遗传因素通过特定的免疫途径影响这些CT感染结果的风险，以及 一些遗传因素可能对两种临床结果都有影响，而另一些因素可能只对其中一种是独一无二的 临床结果。我们研究的长期目标是了解影响免疫遗传因素 CT感染结果为了制定改进预防和管理CT感染的战略， 例如优化衣原体筛查策略和开发衣原体疫苗。 为PI提出的培训计划是由她的项目共同导师William Geisler博士和Dr. 赫曼特·提瓦里。培训计划包括帮助PI在三个主要领域发展的经验：1) CT领域的严谨研究，包括熟悉现有的CT文献， 评估已发表的CT研究、科学完整性原则和负责任的研究行为，以及 严谨性和重复性的方法；2)统计遗传学，包括方法和结果的解释； 3)职业和职业发展，包括学习撰写赠款、审阅期刊、 介绍研究成果并将其转化为临床应用。培训计划的总体目标是 为PI作为一名内科科学家的成功职业生涯奠定坚实的基础，并拥有终极职业生涯 目标是领导一个协作研究团队，弥合基于实验室的研究和 在改善妇女生殖健康成果的背景下进行系统研究。

PROJECT SUMMARY/ABSTRACT The purpose of this NIH F31-Diversity application is to obtain support for the PI, Kristin Olson, for mentored research and career development activities within her MD/PhD degree training that will strengthen her potential to become a successful physician scientist. The project goal is to develop skills in statistical genetics that will allow the PI to study the influence of immunogenetic determinants on Chlamydia trachomatis (CT) infection outcomes in women, including methods of genetic data quality control, imputation, multiple testing corrections, and pathway analyses. The primary objective of the research proposal is to investigate the immunogenetic determinants of Chlamydia trachomatis (CT) reinfection and CT-associated infertility in women. CT infection is the most prevalent sexually transmitted bacterial infection worldwide, including in the U.S. CT disproportionately affects women due to the reproductive morbidity it causes. Up to 20% of women experience reinfection after treatment and inflammation from repeated CT infection episodes can contribute to risk for CT- associated infertility. It is unknown why some women remain susceptible to CT after treatment, leading to reinfection, and why some CT infections lead to infertility. This project seeks to determine genetic risk markers for CT reinfection and CT-related infertility (Aims 1A and 2A), and then utilize complex statistical methods to predict the immune responses mediated by these genetic markers (Aims 1B and 2B). The central hypothesis is that genetic factors influence risk for these CT infection outcomes through specific immunological pathways, and some genetic factors may contribute to both clinical outcomes while others may be unique for only one of the clinical outcomes. The long-term objective of our research is to understand immunogenetic factors that influence CT infection outcomes in order to develop strategies for improving prevention and management of CT infection, such as optimizing chlamydia screening strategies and development of a chlamydia vaccine. The proposed training plan for the PI is sponsored by her project co-mentors, Dr. William Geisler and Dr. Hemant Tiwari. Included in the training plan are experiences that help the PI develop in three major areas: 1) rigorous research in the CT field, including developing familiarity with the existing CT literature, critically evaluating published CT studies, principles of scientific integrity and responsible conduct of research, and methods of rigor and reproducibility; 2) statistical genetics, including methodology and interpretation of results; and 3) career and professional development, including learning skills in grant writing, journal reviewing, presenting, and translation of research findings to clinical applications. The overall goal of the training plan is to provide the PI with a solid foundation for a successful career as a physician scientist, with the ultimate career goal of leading a collaborative research team that bridges the gap between laboratory-based research and systems-based research in the context of improving reproductive health outcomes for women.