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

项目摘要/摘要 候选人：林博士是加州大学伯克利分校的研究科学家约翰(Jack)教授 科尔福德的小组。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。自.以来 2010年，她担任洗涤益处研究的协调微生物学家，这是一项大规模、多领域的研究 评估水、卫生设施、个人卫生和营养的影响的国家分组随机试验 关于儿童健康的干预措施，重点是肠道炎症。这项研究和培训计划建立在她的基础上 在微生物学、免疫学和全球卫生方面有很强的跨学科背景。收获 流行病学和生物统计学方面的经验将有助于她向独立于人口的“替补席”过渡 加州大学伯克利分校的调查员，最终将使她能够实现她的长期职业目标，成为一名 在评估产前和早期生活干预以改善儿童健康方面处于全球卫生领先地位。 环境：加州大学伯克利分校在进行创新和突破性研究方面有着悠久的历史 推进流行病学和生物统计学理论及其在国际卫生中的应用。为了实现她的目标 为了实现职业目标，林博士寻求(1)流行病学方面的培训，重点是因果推断方法(特别是， 直接和间接效应的边际结构模型和目标最大似然估计)(2) 生物统计学和(3)儿童压力与发展。为了实现这些目标，林博士组装了一个独特的 加州大学伯克利分校的跨学科培训和指导团队。杰克·科尔福德(主要导师)将指导 她在流行病学理论和应用方面的培训。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，包括直接和间接影响模型和有针对性的 最大似然估计。利娅·费尔纳德(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：早期生命线性发育迟缓与发育受损有关，但其潜在的 发病机制尚不清楚。亚临床肠道炎症和损害影响生活在 低收入国家，并日益被认为是造成早年恶性循环的潜在主要因素。 生活营养不良和口服疫苗失败。与肠道有关的怀孕风险因素知之甚少 炎症和这些产前因素对线性生长和神经发育的影响。在目标1中，Dr。 林将确定母亲在怀孕期间应激和炎症之间的联系，以及 随后测量儿童肠道炎症和通透性。在《目标2》中，她将评估这段关系 产前应激和炎症与未来儿童线性生长发育之间的关系。她提议 使用现代因果推理方法阐明产前应激和 炎症以儿童肠道炎症为主，线形发育迟缓，发育不良。最终，这位导师 研究将为林博士成功应用R01级药物做好准备，以研究潜在的下游影响 产前应激和炎症对儿童应激、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.