The candidate is a molecular epidemiologist with primary research interest in the programming mechanisms by which prenatal/early-life exposure to environmental and social pollutants influences the health of children, with particular interest n neurodevelopment. With research linking ambient air pollution and poor neurodevelopment, the goal of this proposal is to add to the growing research linking urban air pollutants, stress and poor neurodevelopment by identifying novel mitochondrial (mt) biomarkers through which in utero exposures may be operating to impact future neurodevelopment. Through formal coursework and expert mentorship by Drs. Rosalind Wright, Andrea Baccarelli, Robert Wright, Michelle Bosquet Enlow, Avraham Reichenberg, Luca Lambertini and Liming Lang, this award will enable me to develop the knowledge and skills necessary to become an independent transdisciplinary environmental health scientist and achieve my long-term career goals: to establish a competitive and successfully funded program to study the cumulative effects of environmental exposures (e.g., air pollution/ stress) on the programming of biological mechanisms related to chronic childhood conditions. While this award focuses on neurobehavioral outcomes, it is worth noting that the knowledge and skills obtained will be broadly applicable to a range of child health outcomes given the large number of childhood conditions with mt underpinnings (e.g., asthma, obesity, autism, and attention disorders). Specifically, the candidate will 1) undergo extensive laboratory training in Drs. Baccarelli's and Lambertini's laboratories to further enhance my molecular skills; 2) obtain training in measuring and interpreting interactions involving social stressors; and 3) receive guidance and hands-on training in selecting, administering and interpreting neurodevelopmental assessments across early childhood. The proposed study will be the first to investigate complementary mtDNA biomarkers in two target tissues (e.g., placenta and cord blood) with respect to prenatal environmental exposures (e.g., urban air pollutants and stress) and early neurobehavioral phenotypes. The intent is to use state-of-art analyses of mtDNA damage by means of a panel of complementary markers of oxidative damage, heteroplasmy, and mtDNA abundance measured at the maternal-fetal interface (e.g., placenta and cord blood). These markers have properties that make them exceptionally well suited to biomarker development, as they: 1) have been shown to be altered by the environmental exposures; and 2) can mark the presence of damaged mitochondria, a primary source of systemic oxidative stress to which the brain is particularly vulnerable. This study is also highly cost effective as we will leverage the resources of an existing well-phenotyped urban and ethnically-mixed pregnancy cohort [PRogramming of Intergenerational Stress Mechanisms (PRISM) study] with existing biospecimens and neurobehavioral & environmental data.

Public Health Relevance

The amount of scientific research linking ambient air pollution, stress, and poor neurodevelopment continues to grow; however, very limited resources are available to identify children who are environmentally-compromised and to predict who will experience negative neurodevelopmental outcomes. The proposed research has the potential to identify novel mitochondrial biomarkers to better inform pathways through which in utero environmental/social factors may be operating to impact future neurodevelopment. The knowledge and skills gained from this project will be broadly applicable to a range of child health outcomes given the large number of childhood conditions with mt underpinnings (e.g., asthma, obesity, autism, and attention disorders).

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Career Transition Award (K99)
Project #
5K99ES024116-02
Application #
9056593
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Gray, Kimberly A
Project Start
2015-04-20
Project End
2017-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Pediatrics
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Flom, Julie D; Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon et al. (2018) Maternal Lifetime Trauma and Birthweight: Effect Modification by In Utero Cortisol and Child Sex. J Pediatr 203:301-308
Brunst, Kelly J; Sanchez-Guerra, Marco; Chiu, Yueh-Hsiu Mathilda et al. (2018) Prenatal particulate matter exposure and mitochondrial dysfunction at the maternal-fetal interface: Effect modification by maternal lifetime trauma and child sex. Environ Int 112:49-58
Brunst, Kelly J; Rosa, Maria José; Jara, Calvin et al. (2017) Impact of Maternal Lifetime Interpersonal Trauma on Children's Asthma: Mediation Through Maternal Active Asthma During Pregnancy. Psychosom Med 79:91-100
Lipton, L R; Brunst, K J; Kannan, S et al. (2017) Associations among prenatal stress, maternal antioxidant intakes in pregnancy, and child temperament at age 30 months. J Dev Orig Health Dis 8:638-648
Brunst, Kelly J; Sanchez Guerra, Marco; Gennings, Chris et al. (2017) Maternal Lifetime Stress and Prenatal Psychological Functioning and Decreased Placental Mitochondrial DNA Copy Number in the PRISM Study. Am J Epidemiol 186:1227-1236
Brunst, Kelly J; Baccarelli, Andrea A; Wright, Rosalind J (2015) Integrating mitochondriomics in children's environmental health. J Appl Toxicol 35:976-91
Brunst, Kelly J; Enlow, Michelle Bosquet; Kannan, Srimathi et al. (2014) Effects of Prenatal Social Stress and Maternal Dietary Fatty Acid Ratio on Infant Temperament: Does Race Matter? Epidemiology (Sunnyvale) 4: