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

女性衣原体再感染和衣原体相关不孕症的免疫遗传学决定因素

• 批准号: 9469909
• 负责人: Kristin Marie Olson
• 金额: $ 3.92万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-11-01 至 2021-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9469909
• 关键词: Affect; Aftercare; Animal Model; Area; Bacterial Infections; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Clinical; Complex; Complication; DNA; Development; Doctor of Philosophy; Familiarity; Female infertility; Foundations; Future; Genes; Genetic; Genetic Determinism; Genetic Markers; Genetic Predisposition to Disease; Genetic Risk; Genital system; Genomic DNA; Goals; Grant; Guidelines; HLA-DQB1; Immune; Immune response; Immunity; Immunogenetics; Immunological Models; Immunologics; Infection; Infertility; Inflammation; International; Journals; Laboratories; Lead; Learning Skill; Literature; Major Histocompatibility Complex; Mediating; Mentors; Methodology; Methods; Modeling; Outcome; Pathway Analysis; Pathway interactions; Patients; Physicians; Positioning Attribute; Prevention; Prevention strategy; Process; Publishing; Quality Control; Recommendation; Reporting; Reproducibility; Reproductive Health; Research; Research Methodology; Research Proposals; Risk; Risk Marker; Running; Scientist; Sexually Transmitted Diseases; Single Nucleotide Polymorphism; Solid; Statistical Methods; Statistical Models; System; Testing; Training; Translating; Translational Research; United States National Institutes of Health; Vaccines; Variant; Woman; Work; Writing; base; career; career development; clinical application; data quality; effective therapy; experience; follow-up; genetic variant; immunopathology; improved; novel; novel strategies; predictive marker; prevent; reproductive; reproductive morbidity; research and development; responsible research conduct; screening; seropositive; skills; tool

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.

项目总结/摘要 本NIH F31-多样性申请的目的是为PI Kristin Olson获得支持， 在她的MD/PhD学位培训中指导研究和职业发展活动，这将加强她的能力。 有潜力成为一名成功的医学科学家。该项目的目标是发展统计遗传学方面的技能 使PI能够研究免疫遗传决定簇对沙眼衣原体（CT）的影响 妇女感染结果，包括遗传数据质量控制方法、插补、多重检测 校正和途径分析。研究计划的主要目的是调查 女性沙眼衣原体（CT）再感染和CT相关不孕免疫遗传决定因素 CT感染是全世界最普遍的性传播细菌感染，包括在美国。 由于其造成的生殖疾病，对妇女的影响尤为严重。高达20%的女性 治疗后的再感染和反复CT感染发作引起的炎症可能会增加CT的风险， 相关不孕症。目前尚不清楚为什么有些妇女在治疗后仍然对CT敏感， 再感染，以及为什么一些CT感染会导致不孕症。该项目旨在确定遗传风险标记 CT再感染和CT相关不孕症（目的1A和2A），然后利用复杂的统计方法， 预测由这些遗传标记介导的免疫应答（目的1B和2B）。核心假设是 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， 一些遗传因素可能对两种临床结果都有影响，而另一些遗传因素可能仅对其中一种是独特的。 临床结果。我们研究的长期目标是了解免疫遗传因素， CT感染结果为了制定改善CT感染预防和管理的策略， 例如优化衣原体筛查策略和开发衣原体疫苗。 PI的拟议培训计划由其项目共同导师William Geisler博士和Dr. 赫曼特·蒂瓦里培训计划中包括的经验有助于PI在三个主要领域发展： 在CT领域的严谨研究，包括发展熟悉现有的CT文献，批判性地 评价已发表的CT研究、科学诚信原则和负责任的研究行为，以及 2）统计遗传学，包括方法学和结果解释; 3）职业和专业发展，包括学习撰写基金，期刊评审， 介绍，并将研究成果转化为临床应用。培训计划的总体目标是 为PI提供作为医生科学家的成功职业生涯奠定坚实的基础， 领导一个合作研究团队的目标，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。