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

结核病、艾滋病毒和全球健康领域以患者为导向的研究指导

• 批准号: 10159188
• 负责人: Neel Rajnikant Gandhi
• 金额: $ 18.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10159188
• 关键词: Area; Cause of Death; Cessation of life; Clinical Data; Clinical Research; Clinical Trials; Collaborations; Communicable Diseases; Communities; Country; DNA; DNA Methylation; Data; Development; Diagnosis; Disease; Doctor of Medicine; Drug resistance in tuberculosis; Enrollment; Epidemic; Epidemiology; Epigenetic Process; Exposure to; Extramural Activities; Extreme drug resistant tuberculosis; Funding; Future; Gene Expression; Genetic; Genetic Polymorphism; Genetic study; Genomics; Genotype; Goals; Grant; HIV; HIV/TB; Hepatitis C; Household; Human; Human Genetics; Immunologics; Immunology; Incidence; Individual; Infection; Intervention; K-Series Research Career Programs; Knowledge; Leadership; Leprosy; Link; Location; Mentors; Mentorship; Metabolic; Mid-Career Clinical Scientist Award (K24); Modification; Molecular Epidemiology; Mycobacterium tuberculosis; Participant; Pathogenesis; Pathology; Pathway Analysis; Peripheral Blood Mononuclear Cell; Phenotype; Physicians; Pilot Projects; Plasma; Play; Population; Predisposition; Prevention; Preventive; Prospective Studies; Publications; Research; Research Personnel; Research Training; Resistance; Role; Scientist; Site; Social Network; South Africa; Specimen; Therapeutic; Time; Training; Tuberculosis; Tuberculosis Vaccines; United States National Institutes of Health; Universities; biobank; career; career development; co-infection; cohort; design; epidemiology study; epigenome; extensive drug resistance; genetic variant; genome sequencing; genome wide association study; global health; immune function; innovation; insight; metabolomics; microbial; migration; mortality; next generation; novel; novel diagnostics; patient oriented research; prevent; programs; skills; spatial epidemiology; statistics; therapy design; tool; training opportunity; translational study; transmission process; trend; tuberculosis drugs; whole genome

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.

项目概要/摘要 结核病 (TB) 是全球传染病死亡的主要原因，每 10 人死亡中就有 4 人死于结核病 在艾滋病毒感染者中。尽管在降低结核病发病率和死亡率方面取得了进展， 不幸的是，目前的趋势还不足以实现世卫组织确定的每人结核病病例少于 10 例的目标 到 2035 年人口将达到 100,000。创新研究开发新的诊断、治疗和预防工具 是迫切需要的。因此，培训具有专业知识的下一代科学家进行转化 高负担环境中结核病和结核病/艾滋病毒双重感染的研究是一个重要的优先事项。本次K24的目标 竞争性更新的目的是继续指导临床和转化患者领域有前途的年轻研究人员 以结核病、艾滋病毒和全球健康为导向的研究。我现在的K24已经非常成功的支持了 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K24支持36种出版物， 其中包括 26 篇论文，其中一名受训者为第一作者。学员还成功提交了校外资助， 包括 NIH K 职业发展奖以及从 K 奖过渡到第一笔 R01 补助金。 在这次竞争更新中，我将扩大自己的培训范围：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抵抗力的机制； 2）进一步获得收益 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； 3）增强我的 指导和领导技能，帮助我的学员为以患者为导向的研究职业做好准备。这个额外的 培训将加强我对参加我们正在进行的 R01 研究的学员的指导： 结核病传播中的偶然接触；以及与 Mtb 感染抵抗力相关的宿主遗传多态性。 K24 的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) 评估与 Mtb 感染抵抗力相关的候选 DNA 甲基化位点； 2) 识别 使用表观基因组范围的方法预测结核分枝杆菌感染的抵抗力。来自我的研究 正在进行的 R01 研究和拟议的新试点研究将为与相关因素产生新的见解 结核病传播和结核分枝杆菌感染易感性为流行病学干预措施的制定提供信息 以及减少新的结核分枝杆菌感染数量的预防性治疗。此外，数据和样本 生成将为我的学员提供大量培训机会，以发展他们自己的职业生涯 开发项目。