A bench to population epidemiologic approach to investigating the effects of antenatal stress and inflammation on child gut inflammation, growth, and development

项目总结/摘要 候选人：林博士是加州大学伯克利分校约翰（杰克）教授的研究科学家 科尔福德的团队她于2012年在斯坦福大学完成了微生物学和免疫学博士学位。以来 2010年，她担任WASH效益研究的协调微生物学家，这是一项大规模，多学科， 一项国家随机分组试验，评估水、卫生、个人卫生和营养 儿童健康干预措施，重点是肠道炎症。这项研究和培训计划建立在她 在微生物学，免疫学和全球健康的关系强大的跨学科背景。获得 在流行病学和生物统计学方面的经验将有助于她过渡到一个独立的“人口工作组”。 调查员在加州大学伯克利分校，并最终使她能够实现她的长期职业目标，成为一个 在评估产前和生命早期干预措施以改善儿童健康方面，是全球卫生领域的领导者。 环境：加州大学伯克利分校有着悠久的历史，进行创新和突破性的研究 推动流行病学和生物统计学理论及其在国际卫生领域的应用。实现她 职业目标，林博士寻求培训（1）流行病学，重点是因果推理方法（特别是， 直接和间接效应的边际结构模型和有针对性的最大似然估计）（2） 生物统计学和（3）儿童压力和发展。为了实现这些目标，林博士组建了一个独特的 加州大学伯克利分校的跨学科培训和指导团队。Jack Colford（初级导师）将指导 她在流行病学理论和应用方面的训练。艾伦·哈伯德（共同导师）将指导她的培训， 生物统计学和因果推断方法，包括直接和间接效应模型以及目标模型 最大似然估计Lia Fernald（共同导师）将指导她在儿童发展和压力方面的培训。 研究项目：早期生命线性生长蹒跚与发育受损有关，但其潜在的 发病机制知之甚少。亚临床肠道炎症和损伤影响生活在 越来越多的人认识到，这是造成早期贫穷恶性循环的一个潜在主要因素。 生活营养不良和口服疫苗失败。关于与肠道相关的妊娠风险因素知之甚少。 炎症以及这些产前因素对线性生长和神经发育的影响。在目标1中，博士 林将确定怀孕期间母亲压力和炎症之间的联系， 随后测量儿童肠道炎症和渗透性。在目标2中，她将评估 产前压力和炎症与未来儿童线性生长发育之间的关系。她建议 使用现代因果推理方法来阐明产前压力的潜在途径， 儿童肠道炎症，线性增长步履蹒跚，发展不佳。最终，这指导了 林博士的研究将为R 01级的成功应用做好准备，以研究潜在的下游影响 产前压力和炎症对儿童压力、炎症和感染易感性的影响。

PROJECT SUMMARY / ABSTRACT Candidate: Dr. Lin is a research scientist at the University of California, Berkeley in Professor John (Jack) Colford's group. She completed her PhD in Microbiology and Immunology at Stanford University in 2012. Since 2010, she has worked as the coordinating microbiologist for the WASH Benefits study, a large-scale, multi- country cluster randomized trial evaluating the impact of water, sanitation, hygiene, and nutritional interventions on child health, with a focus on gut inflammation. This research and training plan builds on her strong interdisciplinary background at the nexus of microbiology, immunology, and global health. Gaining experience in epidemiology and biostatistics will facilitate her transition to a `bench to population' independent investigator at UC Berkeley and will ultimately enable her to achieve her long-term career goal to become a global health leader in the evaluation of antenatal and early life interventions to improve child health. Environment: UC Berkeley has a long history of conducting innovative and groundbreaking research advancing epidemiological and biostatistical theory and application in international health. To achieve her career goal, Dr. Lin seeks training in (1) epidemiology, with a focus on causal inference methods (in particular, marginal structural models for direct and indirect effects and targeted maximum likelihood estimation) (2) biostatistics and (3) child stress and development. To achieve these goals, Dr. Lin has assembled a unique interdisciplinary training and mentoring team based at UC Berkeley. Jack Colford (primary mentor) will guide her training in epidemiological theory and application. Alan Hubbard (co-mentor) will guide her training in biostatistics and causal inference methods including models for direct and indirect effects and targeted maximum likelihood estimation. Lia Fernald (co-mentor) will guide her training in child development and stress. Research Project: Early life linear growth faltering is associated with impaired development, but its underlying pathogenesis is poorly understood. Subclinical intestinal inflammation and damage affects children living in low-income countries and is increasingly recognized as a potential main contributor to the vicious cycle of early life malnutrition and oral vaccine failure. Little is known about the pregnancy risk factors associated with gut inflammation and the impact of these antenatal factors on linear growth and neurodevelopment. In Aim 1, Dr. Lin will determine the association between maternal stress and inflammation during pregnancy and subsequent measures of child gut inflammation and permeability. In Aim 2, she will evaluate the relationship between antenatal stress and inflammation and future child linear growth and development. She proposes to use modern causal inference methods to elucidate the potential pathways from antenatal stress and inflammation to child gut inflammation, linear growth faltering, and poor development. Ultimately, this mentored research will prepare Dr. Lin for a successful R01-level application to investigate potential downstream effects of antenatal stress and inflammation on child stress, inflammation, and susceptibility to infections.