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: 9898222
• 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/9898222
• 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.

项目摘要 /摘要 结核病（TB）是全球传染病死亡的主要原因，在10例死亡中有4个 在艾滋病毒感染者中。尽管在降低结核病的发病率和死亡率方面取得了进展，但 当前的趋势严重不足以实现WHO End TB目标少于10个TB案例的目标 到2035年，100,000人口。开发新诊断，治疗和预防工具的创新研究 非常需要。因此，培训具有专业知识的下一代科学家进行翻译 在高负担环境中对结核病和结核病/艾滋病毒共同感染的研究是重要的重点。这个K24的目标 竞争性更新将继续指导有前途的临床和转化患者的年轻研究者 - 在结核病，艾滋病毒和全球健康方面进行的研究。我目前的K24在支持方面非常成功 33名学员的指导，并允许我大大扩展我的研究计划，以包括 分子流行病学，结核病免疫学和临床试验。当前的K24支持36个出版物， 包括26名受训者作为第一作者。受训者也成功地提交了壁外赠款， 包括NIH K职业发展奖和从K奖到其第一个R01赠款的过渡。 在这种竞争性的续约中，我将把自己的培训扩展到：1）了解人类遗传学和如何 表观遗传学可以阐明敏感性和对MTB感染的抗性的机制； 2）进一步增加 空间流行病学和空间统计学方面的专业知识，以告知TB传播研究； 3）增强我的 指导和领导能力，以准备我的学员从事以患者为导向的研究。这个附加 培训将增强我对参与我们正在进行的R01研究的学员的指导： 结核病传输中的随意接触；和与MTB感染的抗性有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，研究了两个新的特定研究目的： 1）评估候选DNA甲基化位点与MTB感染的抗性相关； 2）确定 使用表观基因组范围的方法，对MTB感染的抗性表观遗传学预测指标。我的研究 正在进行的R01研究和拟议的新试点研究将产生与与因素相关的因素的新见解。 结核病的传播和对MTB感染的敏感性，以告知流行病学干预的发展 以及预防性治疗，以减少新的MTB感染的数量。此外，数据和标本 生成的将为我的受训者提供许多培训机会，以发展自己的职业 开发项目。