The Toxic Environment and the Epigenetics of Fetal Growth

Summary

Principal Investigator: HEATHER HERSON BURRIS
Abstract: 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. Public Health Relevance: Poor fetal growth is associated with short-term perinatal morbidity and mortality as well as long-term poor health later in life. Arsenic exposure during pregnancy has been shown to potentially inhibit fetal growth in animals and to be associated with low birth weights in humans. Understanding the biology of arsenic toxicity and its effect on fetal growth may ultimately spurn tighter environmental regulation policies, trigger clean-up efforts and allow for targeted therapies during pregnancies affected by high arsenic exposure.
Funding Period: 2012-12-01 - 2017-10-31
more information: NIH RePORT

Top Publications

  1. pmc Association between birth weight and DNA methylation of IGF2, glucocorticoid receptor and repetitive elements LINE-1 and Alu
    Heather H Burris
    Department of Neonatology, Beth Israel Deaconess Medical Center and Division of Newborn Medicine, Boston Children s Hospital, Harvard Medical School, Boston, MA, USA
    Epigenomics 5:271-81. 2013
  2. pmc Environmental epigenetics: from novelty to scientific discipline
    Heather H Burris
    Department of Neonatology, Beth Israel Deaconess Medical Center and Division of Newborn Medicine, Boston Children s Hospital, Harvard Medical School, Boston, MA, USA
    J Appl Toxicol 34:113-6. 2014
  3. ncbi Vitamin D status among preterm and full-term infants at birth
    Heather H Burris
    1 Harvard Medical School, Boston, Massachusetts 2 Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 3 Division of Newborn Medicine, Boston Children s Hospital, Boston, Massachusetts
    Pediatr Res 75:75-80. 2014
  4. pmc Vitamin D and gestational diabetes mellitus
    Heather H Burris
    Department of Neonatology, Beth Israel Deaconess Medical Center, and Division of Newborn Medicine, Boston Children s Hospital and Harvard Medical School, 330 Brookline Avenue, RO 318, Boston, MA, 02215, USA
    Curr Diab Rep 14:451. 2014
  5. ncbi US provider-reported diet and physical activity counseling to pregnant and non-pregnant women of childbearing age during preventive care visits
    Ayae Yamamoto
    Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
    Matern Child Health J 18:1610-8. 2014
  6. pmc Vitamin D status and hypertensive disorders in pregnancy
    Heather H Burris
    Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA Division of Newborn Medicine, Boston Children s Hospital, MA Harvard Medical School, Boston, MA Electronic address
    Ann Epidemiol 24:399-403.e1. 2014

Research Grants

Detail Information

Publications6

  1. pmc Association between birth weight and DNA methylation of IGF2, glucocorticoid receptor and repetitive elements LINE-1 and Alu
    Heather H Burris
    Department of Neonatology, Beth Israel Deaconess Medical Center and Division of Newborn Medicine, Boston Children s Hospital, Harvard Medical School, Boston, MA, USA
    Epigenomics 5:271-81. 2013
    ..We examined the association between birth weight and methylation in the imprinted IGF/H19 loci, the nonimprinted gene NR3C1 and repetitive element DNA (LINE-1 and Alu)...
  2. pmc Environmental epigenetics: from novelty to scientific discipline
    Heather H Burris
    Department of Neonatology, Beth Israel Deaconess Medical Center and Division of Newborn Medicine, Boston Children s Hospital, Harvard Medical School, Boston, MA, USA
    J Appl Toxicol 34:113-6. 2014
    ..Understanding the epigenetic implications of our actions and exposures may benefit generations to come...
  3. ncbi Vitamin D status among preterm and full-term infants at birth
    Heather H Burris
    1 Harvard Medical School, Boston, Massachusetts 2 Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 3 Division of Newborn Medicine, Boston Children s Hospital, Boston, Massachusetts
    Pediatr Res 75:75-80. 2014
    ..We aimed to determine the associations between 25(OH)D levels and gestational age...
  4. pmc Vitamin D and gestational diabetes mellitus
    Heather H Burris
    Department of Neonatology, Beth Israel Deaconess Medical Center, and Division of Newborn Medicine, Boston Children s Hospital and Harvard Medical School, 330 Brookline Avenue, RO 318, Boston, MA, 02215, USA
    Curr Diab Rep 14:451. 2014
    ....
  5. ncbi US provider-reported diet and physical activity counseling to pregnant and non-pregnant women of childbearing age during preventive care visits
    Ayae Yamamoto
    Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
    Matern Child Health J 18:1610-8. 2014
    ..Our data suggest that there may be missed opportunities to provide diet/exercise counseling and that increasing rates of counseling could result in improved maternal and infant health outcomes. ..
  6. pmc Vitamin D status and hypertensive disorders in pregnancy
    Heather H Burris
    Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA Division of Newborn Medicine, Boston Children s Hospital, MA Harvard Medical School, Boston, MA Electronic address
    Ann Epidemiol 24:399-403.e1. 2014
    ..Several studies have reported increased risk of preeclampsia when 25-hyrdoxyvitamin D (25[OH]D) levels are low. The extent to which 25(OH)D may lower risk for hypertensive disorder during pregnancy remains unclear...

Research Grants30

  1. Epigenetic Effects of Prenatal Arsenic Exposure and Fetal Growth
    Molly L Kile; Fiscal Year: 2013
    ..The proposed studies will fill important research gaps in our knowledge of arsenic toxicity and its impact on fetal growth that could inform both clinical and public health interventions in developing and developed countries. ..
  2. Jules Stein Eye Institute Core Grant for Vision Research
    Wayne L Hubbell; Fiscal Year: 2013
    ..Support in the form of the Core grant is requested to maintain these Modules through instrument service contracts, and to provide necessary personnel support to assist and train users and provide routine maintenance. ..