The Toxic Environment and the Epigenetics of Fetal Growth

有毒环境与胎儿生长的表观遗传学

• 批准号: 9619702
• 负责人: Heather Herson Burris
• 金额: $ 10.42万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2018-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9619702
• 关键词: Toxic; Environment; Epigenetics; Fetal; Growth

DESCRIPTION (provided by applicant): This application for a K23 Mentored Patient-Oriented Research Career Development Award includes a 5-year plan for training and research activities that will provide the skills and experience needed to achieve success as an independent investigator studying the role of the environment and epigenetic mechanisms in birth outcomes. The candidate has completed research and clinical fellowships that prepared her for an academic career studying perinatal social epidemiology and is currently a full-time faculty member in the Department of Neonatology at Beth Israel Deaconess Medical Center. The candidate is a core member of the Division of Newborn Medicine at Harvard Medical School serving as an Instructor in pediatrics, which is the standard entry level academic position at Harvard. This K23 award will provide her with the structure and support necessary to accomplish the following goals: (1) assess the role that arsenic plays in fetal growth; (2) assess the role arsenic plays in the DNA methylation of genes involved in fetal growth such as inflammatory cytokine genes and the glucocorticoid receptor gene, and explore whether arsenic affects fetal growth through such epigenetic mechanisms; (3) gain expertise in environmental toxicology and environmental epigenetic analyses; and (4) learn the administrative skills needed to manage a large cohort study so that transition to an independent research career running her own birth cohort is accomplished. The candidate's goal is to examine the role the toxic chemical environment plays in birth outcome disparities in the US. To achieve these goals, Dr. Burris has assembled a mentoring team comprised of a primary mentor, Robert Wright, MD MPH, Associate Professor of Pediatrics and Environmental Health who is an expert in pediatric environmental health and toxicology, and co-mentor Andrea Baccarelli, MD PhD, the Mark and Catherine Winkler Associate Professor of Environmental Epigenetics, who has expertise in epigenetic analyses. Although chemicals like arsenic are known to affect birth outcomes and known to affect DNA methylation, it remains unknown whether DNA methylation mediates arsenic-birth weight associations. The study proposed is designed to test the hypothesis that arsenic impairs fetal growth, that arsenic causes alterations in the DNA methylation of inflammatory cytokine genes and the glucocorticoid receptor gene. The candidate will explore whether DNA methylation disturbances mediate arsenic-birth weight associations. These analyses will be performed within a previously established, currently funded cohort in Mexico City (ELEMENT) directed by Dr. Wright. The candidate will use the abundant resources available at Beth Israel Deaconess Medical Center, the Harvard Catalyst (Clinical and Translational Science Center) and the Harvard School of Public Health to obtain the training and coursework necessary to supplement the practical training attained through these analyses to become an independent investigator with a research program studying the environmental impact on birth outcome disparities.

描述（由申请人提供）：本申请K23指导的以患者为导向的研究职业发展奖包括一项为期5年的培训和研究活动计划，该计划将提供成功的技能和经验，作为独立研究者，研究环境和表观遗传机制在出生结果中的作用。候选人已经完成了研究和临床研究金，为她的学术职业做好了准备，正在研究围产期社会流行病学，目前是贝丝·以色列女执事医疗中心新生儿学系的全职教职员工。该候选人是哈佛医学院新生儿医学系的核心成员，担任儿科讲师，这是哈佛的标准入门级学术职位。该K23奖将为她提供实现以下目标所需的结构和支持：（1）评估砷在胎儿生长中的作用； （2）评估砷在参与胎儿生长的基因的DNA甲基化中的作用，例如炎性细胞因子基因和糖皮质激素受体基因，并探索砷是否通过这种表观遗传机制来影响胎儿的生长； （3）获得环境毒理学和环境表观遗传分析方面的专业知识； （4）了解管理大型队列研究所需的行政技能，以便完成经营自己的出生队列的独立研究职业。候选人的目标是研究有毒化学环境在美国的出生结果差异中所起的作用。 To achieve these goals, Dr. Burris has assembled a mentoring team comprised of a primary mentor, Robert Wright, MD MPH, Associate Professor of Pediatrics and Environmental Health who is an expert in pediatric environmental health and toxicology, and co-mentor Andrea Baccarelli, MD PhD, the Mark and Catherine Winkler Associate Professor of Environmental Epigenetics, who has expertise in epigenetic分析。尽管已知砷等化学物质会影响出生结果并已知会影响DNA甲基化，但尚不清楚DNA甲基化是否介导了砷生物出生的体重关联。该研究旨在检验砷会损害胎儿生长的假设，即砷会导致炎性细胞因子基因和糖皮质激素受体基因的DNA甲基化改变。候选人将探索DNA甲基化是否会介导砷生殖体重关联。这些分析将在赖特博士执导的先前建立的，目前由墨西哥城（Element）的同类人群中进行。候选人将使用贝丝以色列执事医疗中心，哈佛大学催化剂（临床和转化科学中心）和哈佛公共卫生学院获得丰富的资源，以获取所需的培训和课程，以补充通过这些分析获得的实践培训，以成为一项独立的研究人员，并通过研究环境对出生结果的影响进行研究。