Mentorship in Patient-Oriented Research in Tuberculosis, HIV and Global Health

项目摘要/摘要 结核病是全球传染病死亡的主要原因，占死亡人数的十分之四。 在感染艾滋病毒的人身上。尽管在降低结核病发病率和死亡率方面取得了进展， 可悲的是，目前的趋势不足以实现世卫组织结束结核病的目标，即每年不到10例结核病病例 到2035年，人口将达到10万。创新研究，开发新的诊断、治疗和预防工具 都是非常需要的。因此，培养具有专业知识的下一代科学家进行翻译 在高负担环境下研究结核病和结核病/艾滋病毒混合感染是一项重要的优先事项。这款K24的目标是 竞争更新是继续指导有前途的年轻临床和转化型患者研究人员- 面向结核病、艾滋病毒和全球健康的研究。我现在的K24已经非常成功地支持 为33名学员提供指导，并允许我大幅扩展我的研究计划，以包括 分子流行病学、结核病免疫学和临床试验。目前的K24支持36种出版物， 包括26篇以第一作者为指导对象的文章。学员还成功地提交了校外赠款， 包括NIH K职业发展奖，并从K奖过渡到他们的第一个R01奖。 在这次竞争性更新中，我将扩大我自己的培训范围，以：1)了解人类遗传学和 表观遗传学可以阐明对结核分枝杆菌感染的易感性和耐药性的潜在机制；2)进一步获得 在空间流行病学和空间统计方面的专门知识，为结核病传播研究提供信息；以及3)加强我的 指导和领导技能，为我的受训人员在以患者为导向的研究中的职业生涯做好准备。这是额外的 培训将加强我对参与我们正在进行的R01研究的受训者的指导： 结核病传播中的偶然接触；与结核分枝杆菌感染抵抗力相关的宿主基因多态。 K24的延续还将促进一项试验性表观遗传学研究，调查两个新的具体研究目标： 1)评估候选DNA甲基化位点与结核分枝杆菌感染抵抗力的关系；以及2)确定 用表观基因组方法预测结核分枝杆菌感染抗性的表观遗传学预测因子。来自我的研究 正在进行的R01研究和拟议的新试点研究将对与以下因素相关的因素产生新的见解 结核病传播和对结核分枝杆菌感染的易感性，为流行病学干预措施的发展提供信息 和预防性治疗，以减少新的结核分枝杆菌感染数量。此外，数据和标本 将为我的学员提供大量的培训机会，帮助他们发展自己的职业生涯 发展项目。

PROJECT SUMMARY / ABSTRACT Tuberculosis (TB) is the leading cause of infectious disease death globally, and accounts for 4 out of 10 deaths in HIV-infected individuals. Although progress has been made in decreasing incidence and mortality from TB, the current trends are woefully insufficient to achieve the WHO End TB goal of fewer than 10 TB cases per 100,000 population by 2035. Innovative research to develop new diagnostic, therapeutic and prevention tools are critically needed. Thus, training the next generation of scientists with expertise to carry out translational studies in TB and TB/HIV co-infection in high burden settings is an important priority. The goal of this K24 competitive renewal is to continue to mentor promising young investigators in clinical and translational patient- oriented research in TB, HIV and Global Health. My current K24 has been very successful in supporting mentorship for 33 trainees, and in allowing me to expand my research program substantially to include molecular epidemiology, TB immunology and clinical trials. The current K24 supported 36 publications, including 26 with a mentee as first author. Mentees were also successful in submitting extramural grants, including NIH K career development awards and making the transition from K awards to their first R01 grants. In this competitive renewal, I will expand my own training to: 1) understand how human genetics and epigenetics can elucidate mechanisms underlying susceptibility and resistance to Mtb infection; 2) gain further expertise in spatial epidemiology and spatial statistics to inform studies of TB transmission; and 3) enhance my mentorship and leadership skills to prepare my trainees for careers in patient-oriented research. This additional training will enhance my mentorship of trainees participating in our ongoing R01 studies examining: the role of casual contact in TB transmission; and host genetic polymorphisms associated with resistance to Mtb infection. The K24 continuation will also facilitate a pilot epigenetic study investigating two novel specific research aims: 1) to assess candidate DNA methylation sites for association with resistance to Mtb infection; and 2) to identify epigenetic predictors of resistance to Mtb infection using an epigenome-wide approach. The research from my ongoing R01 studies and the proposed new pilot study will generate novel insights into factors associated with TB transmission and susceptibility to Mtb infection to inform the development of epidemiologic interventions and preventive therapeutics to reduce the number of new Mtb infections. Further, the data and specimens generated will provide numerous training opportunities for my mentees to develop their own career development projects.