Perinatal Exposures, Tissue- and Cell-specific Epigenomics, & Lifecourse Outcomes

围产期暴露、组织和细胞特异性表观基因组学、

基本信息

  • 批准号:
    9545289
  • 负责人:
  • 金额:
    $ 119.09万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-06-01 至 2020-04-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Toxicant exposures early in life adversely affect health outcomes in both animals and humans, in part due to epigenetic mechanisms (e.g. DNA methylation). Studies also indicate that exposures' impact on the epigenome can be tissue and even cell specific. Yet, epigenetic epidemiology analysis of toxicants is often limited to biologically available or "surrogate" (e.g. blood, saliva) samples, which serve as proxies for epigenetic status in tissues targeted by exposures. While methylation of peripheral DNA may not mirror that of all tissues, it has been used as a biomarker associated with both disease and exposures. Using bisphenol A and phthalates (e.g. DEHP) as representative toxicants, our overall objective is to utilize mouse models to evaluate tissue- and cell-specific epigenetic alterations associated with perinatal exposures and disease outcomes, including tissues not feasibly assessed in humans. We leverage resources by utilizing tissues funded as part of the Michigan NIEHS/EPA-funded Children's Environmental Health P01 Center in which epigenetic analysis in target tissues focuses on candidate metastable epialleles and imprinted genes, two sets of loci most vulnerable to environmental changes. Within TaRGET II U01, we will extend analysis genome- wide to 11 tissue and cell types to map DNA methylation (5mC), hydroxymethylation (5hmC), and gene expression in an effort to inform epigenetic epidemiology studies with an environmental focus. We use sample sizes powered to detect sex differences and conduct methylome and transcriptome analyses immediately following perinatal exposure at post-natal day 22 in target tissues from the three germ layers (brain & breast from ectoderm, kidney from mesoderm, & liver from endoderm) and in surrogate tissues of human relevance (hair, peripheral blood leukocytes, & stool), as well as longitudinally at 8 months of age to identify exposure- dependent epigenetic changes that persist into adulthood. Capitalizing on our team's expertise in cell-specific epigenetics, we also include 4 purified cell populations to furthr compare target cells to surrogates. Ultimately, we seek to identify a subset of tissue-independent labile genes, which represent regions of the epigenome vulnerable early in life, and may be interrogated, with the use of surrogate tissues.


项目成果

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Dana Dolinoy其他文献

Dana Dolinoy的其他文献

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{{ truncateString('Dana Dolinoy', 18)}}的其他基金

MI-CARES: The Michigan Cancer and Research on the Environment Study
MI-CARES:密歇根癌症与环境研究
  • 批准号:
    10491837
  • 财政年份:
    2021
  • 资助金额:
    $ 119.09万
  • 项目类别:
MI-CARES: The Michigan Cancer and Research on the Environment Study
MI-CARES:密歇根癌症与环境研究
  • 批准号:
    10336238
  • 财政年份:
    2021
  • 资助金额:
    $ 119.09万
  • 项目类别:
Environmental Epigenomics and Precision Environmental Health
环境表观基因组学和精准环境健康
  • 批准号:
    10376363
  • 财政年份:
    2020
  • 资助金额:
    $ 119.09万
  • 项目类别:
Environmental Epigenomics and Precision Environmental Health
环境表观基因组学和精准环境健康
  • 批准号:
    10623309
  • 财政年份:
    2020
  • 资助金额:
    $ 119.09万
  • 项目类别:
Environmental Epigenomics and Precision Environmental Health
环境表观基因组学和精准环境健康
  • 批准号:
    10162591
  • 财政年份:
    2020
  • 资助金额:
    $ 119.09万
  • 项目类别:
Perinatal Exposures, Tissue- and Cell-specific Epigenomics, & Lifecourse Outcomes
围产期暴露、组织和细胞特异性表观基因组学、
  • 批准号:
    9097203
  • 财政年份:
    2016
  • 资助金额:
    $ 119.09万
  • 项目类别:
2015 Cellular and Molecular Mechanisms of Toxicology Gordon Research Conference & Gordon Research Seminar
2015毒理学细胞和分子机制戈登研究会议
  • 批准号:
    8895591
  • 财政年份:
    2015
  • 资助金额:
    $ 119.09万
  • 项目类别:
Development of piRNAs for target-specific methylation
开发用于靶标特异性甲基化的 piRNA
  • 批准号:
    8947514
  • 财政年份:
    2015
  • 资助金额:
    $ 119.09万
  • 项目类别:
Environmental exposures in early life: Epigenetics and neurodevelopment
生命早期的环境暴露:表观遗传学和神经发育
  • 批准号:
    8765374
  • 财政年份:
    2014
  • 资助金额:
    $ 119.09万
  • 项目类别:
Heat-related illness and farmworker’s health: Climate change and precarious employment
与高温相关的疾病和农场工人的健康:气候变化和不稳定的就业
  • 批准号:
    10696431
  • 财政年份:
    2011
  • 资助金额:
    $ 119.09万
  • 项目类别:

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