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

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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.