Mentoring Translational Researchers for Careers in Pediatric Global Health

描述(由申请人提供)：近年来，申请医学院、住院医生项目和传染病奖学金的人对全球健康的兴趣大大增加，但将这种兴趣转化为成功的学术生涯的职业发展道路仍然定义不清，而且存在危险，学术界可用的导师相对较少。K24奖的候选人是一位儿科学和医学副教授，他建立了一个资助的研究计划，以调查儿童疟疾的免疫反应，并在体外确定高传播环境下儿童保护性免疫的相关性。这项研究计划建立在与在乌干达工作的领先疟疾流行病学家和临床试验人员的密切合作关系的基础上。PI和她的合作者已经建立了一支有效的多学科团队，并建立了大量的研究基础设施，以便在乌干达托罗罗进行实地研究，那里的疟疾传播强度非常高。疟疾是乌干达儿童死亡的主要原因，每年夺走全世界100多万儿童的生命。不言而喻，需要一种有效的疟疾疫苗。然而，疫苗开发、改进和测试的迭代过程将大大有助于更好地了解赋予疟疾保护作用的免疫效应机制，以及可能阻碍持久免疫发展的免疫颠覆机制。我们目前对疟疾免疫保护机制的了解非常有限，主要来自动物和人类的实验性疫苗接种研究。到目前为止，对自然暴露于疟疾的儿童中疟疾特异性T细胞反应的基于人群的研究数量很少，而且受到研究设计缺陷的限制。拟议的研究将使用从特征明确的儿科队列中获得的样本，以确定疟疾保护性免疫的相关性，并确定化学预防干预和产前暴露于疟疾和艾滋病毒如何改变抗疟疾免疫的自然获得。此外，这一奖项将使候选人能够进入新的调查领域 包括半天然T细胞在疟疾感染和临床耐受性中的作用。K24的主要目标是培养一批年轻的研究人员，他们拥有进行高质量翻译免疫学研究所需的技能，鼓励他们对以患者为导向的全球卫生研究的热情，并帮助他们成为成功的独立调查人员。受训人员将包括美国各级内科科学家--传染病研究员、博士后学者、住院医生和学生--与乌干达科学家和学生并肩工作，在疟疾传播强度极高的地区进行创新的免疫学研究，同时使美国和乌干达的研究人员能够合作团队。

DESCRIPTION (provided by applicant): Interest in global health among applicants to medical schools, residency programs, and infectious disease fellowships has grown enormously in recent years, but the career development pathways for translating this interest into successful academic careers remain poorly defined and perilous, with relatively few mentors available in academia. The candidate for this K24 Award is an Associate Professor of Pediatrics and Medicine who has established a funded research program to investigate the immune response to childhood malaria and identify in vitro correlates of protective immunity among children in high transmission settings. This research program is based upon strong collaborative relationships with leading malaria epidemiologists and clinical trialists working in Uganda. The PI and her collaborators have forged an effective multidisciplinary team and have built substantial research infrastructure to conduct field studies in Tororo, Uganda, a setting of exceptionally high malaria transmission intensity. Malaria is the leading cause of pediatric deaths in Uganda and claims the life of more than one million children worldwide each year. The need for an effective vaccine against malaria is self-evident. However the iterative process of vaccine development, refinement, and testing would be greatly aided by a better understanding of the immunologic effector mechanisms that confer protection from malaria, as well as immune subversion mechanisms that may hinder the development of durable immunity. Our current understanding of the mechanisms of immune protection from malaria is very limited, and comes mostly from experimental vaccination studies of animals and humans. To date, population-based studies of the malaria-specific T cell response among children naturally exposed to malaria have been few in number and limited by shortcomings in study design. The proposed studies will use samples obtained from well-characterized pediatric cohorts to identify correlates of protective immunity to malaria, and to determine how the natural acquisition of antimalarial immunity is altered by chemopreventive interventions and by prenatal exposure to malaria and to HIV. In addition, this award will enable the candidate to branch into new areas of investigation including the role of semi-innate ?¿ T cells in malaria infection and clinical tolerance. The primary goal of this K24 will be to develop a cohort of young investigators with the skills require to conduct high quality translational immunology research, encourage their passion for patient-oriented global health research, and help them to become successful independent investigators. Trainees will include U.S. physician scientists at all levels - infectious disease fellows, post-doctoral scholars, residents, and students - working side by side with Ugandan scientists and students to conduct innovative immunology research in a region of exceptionally high malaria transmission intensity, while capacitating U.S. and Ugandan researchers to work in collaborative teams.