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

研究产前应激和炎症对儿童肠道炎症、生长和发育影响的人群流行病学方法

• 批准号: 10213607
• 负责人: Audrie Lin
• 金额: $ 12.53万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-06 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10213607
• 关键词: 5 year old; Adopted; Adult; Affect; Age; Area; Bangladesh; Biological; Biological Markers; Biometry; C-reactive protein; California; Child; Child Development; Child Health; Cluster randomized trial; Country; Critical Pathways; Data; Development; Dietary Intervention; Disease; Doctor of Philosophy; Environment; Epidemiology; Evaluation; F2-Isoprostanes; Failure; Functional disorder; Funding; Future; Gap Junctions; Goals; Grant; Growth; Growth and Development function; Handwashing; Health; Hydrocortisone; Hygiene; Immunology; Impairment; Infant; Infection; Infectious Diseases Research; Inflammation; Insulin-Like Growth Factor I; International; Intervention; Intestinal permeability; Lactulose; Lead; Length; Life; Machine Learning; Malnutrition; Mannitol; Maternal Exposure; Measurement; Measures; Mentors; Mentorship; Methods; Microbiology; Modeling; Modernization; Molecular; Molecular Biology; Mucous Membrane; Neopterin; Nutritional; Observational Study; Orosomucoid; Outcome; Pathogenesis; Pathway interactions; Peroxidases; Physiology; Population; Predisposition; Pregnancy; Prognostic Marker; Public Health; Randomized; Recording of previous events; Research; Research Personnel; Research Project Grants; Research Training; Risk; Risk Factors; Rural; Sampling; Sanitation; Scientist; Small Intestines; Stress; Structural Models; Surface; Surveys; Testing; Training; Treatment Efficacy; Universities; Villous Atrophy; Water; Work; absorption; alpha 1-Antitrypsin; antenatal; base; biomarker discovery; career; cytokine; efficacy evaluation; efficacy trial; experience; fetal programming; global health; improved; inflammatory disease of the intestine; innovation; low income country; maternal stress; neurodevelopment; oral vaccine; prevent; professor; prospective; repository; socioeconomics; theories; therapy development

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.

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） 科尔福德的小组。自2012年以来，她在斯坦福大学完成了微生物和免疫学博士学位。 2010年，她曾是Wash Beasent研究的协调微生物学家 国家群集随机试验评估水，卫生，卫生和营养的影响 对儿童健康的干预措施，重点是肠道炎症。这个研究和培训计划以她为基础 在微生物学，免疫学和全球健康状况的联系上，有力的跨学科背景。获得 流行病学和生物统计学方面的经验将促进她向独立的“基准向人口”的过渡 加州大学伯克利分校的调查员最终将使她能够实现自己的长期职业目标，成为一个 全球卫生领导者评估产前和早期生活干预措施以改善儿童健康。 环境：加州大学伯克利分校有悠久的创新和开创性研究的历史 推进国际健康中的流行病学和生物统计学理论和应用。实现她 职业目标，林博士寻求（1）流行病学培训，重点是因果推理方法（尤其是 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）儿童压力和发育。为了实现这些目标，林博士汇集了一个独特的 位于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（Alan Hubbard）（联盟）将指导她的培训 生物统计学和因果推理方法，包括直接和间接效应的模型，并针对性 最大似然估计。莉亚·费尔纳德（Lia Fernald）（联合学）将指导她在儿童发育和压力方面的培训。 研究项目：早期生命线性增长步履蹒跚与发展受损有关，但其基础 发病机理知之甚少。亚临床肠道炎症和损害影响着生活的儿童 低收入国家，越来越多地被认为是造成早期恶性循环的潜在主要贡献者 生命营养不良和口服疫苗衰竭。关于与肠道相关的妊娠危险因素知之甚少 炎症以及这些产前因素对线性生长和神经发育的影响。在AIM 1中，博士 林将确定孕产妇应力与怀孕期间炎症之间的关联 随后的儿童肠道炎症和渗透性的措施。在AIM 2中，她将评估关系 在产前压力与炎症与未来的儿童线性生长和发育之间。她建议 使用现代因果推理方法来阐明产前应力和 儿童肠道炎症，线性生长的炎症和发育不良。最终，这得到了指导 研究将为Lin博士准备成功的R01级应用，以研究潜在的下游效果 产前应力和儿童压力，炎症和感染易感性的炎症。