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

项目概要/摘要 结核病（TB）是全球传染病死亡的主要原因，占死亡人数的十分之四 在HIV感染者身上。虽然在降低结核病发病率和死亡率方面取得了进展， 目前的趋势远远不足以实现世卫组织消灭结核病的目标，即每年减少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 是非常需要的。因此，培养下一代具有专业知识的科学家， 在高负担环境中开展结核病和结核病/艾滋病毒合并感染的研究是一个重要的优先事项。K24的目标是 竞争性更新是继续指导有前途的年轻研究人员在临床和翻译病人- 结核病、艾滋病和全球健康领域的研究。我目前的K24已经非常成功地支持 导师为33名学员，并允许我扩大我的研究计划，大大包括 分子流行病学、结核免疫学和临床试验。当前的K24支持36篇出版物， 其中26篇以学员为第一作者。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R 01赠款。 在这次竞争性的更新中，我将扩大我自己的培训：1）了解人类遗传学和 表观遗传学可以阐明Mtb感染的易感性和耐药性的机制; 2）进一步获得 空间流行病学和空间统计学方面的专业知识，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，为我的学员在以病人为导向的研究事业做好准备。该附加 培训将加强我对参加我们正在进行的R 01研究的学员的指导： 结核病传播中的偶然接触;与耐结核分枝杆菌感染相关的宿主遗传多态性。 K24延续还将促进一项试点表观遗传学研究，调查两个新的具体研究目标： 1)评估候选DNA甲基化位点与抗结核分枝杆菌感染的关联;和2）鉴定 使用表观基因组全方法的耐结核分枝杆菌感染的表观遗传预测因子。我的研究 正在进行的R 01研究和拟议的新的试点研究将产生新的见解，与 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制定提供信息 和预防性治疗，以减少新的结核病感染的数量。此外，数据和样本 将为我的学员提供大量培训机会，以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.