Neurodevelopment and Improving Children's Health following EtS exposure (NICHES)

EPA Grant Number: R835437
Center: The Center for Study of Neurodevelopment and Improving Children's Health
Center Director: Murphy, Susan K.
Title: Neurodevelopment and Improving Children's Health following EtS exposure (NICHES)
Investigators: Murphy, Susan K.
Institution: Duke University
EPA Project Officer: Louie, Nica
Project Period: June 1, 2013 through May 31, 2018
Project Amount: $3,907,780
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2012) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

The Center for Study of Neurodevelopment and Improving Children's Health following EtS exposure (NICHES) will investigate mechanistic relationships between environmental tobacco smoke (ETS) exposure and developmental neurocognitive impairments including Attention-Deficit/ Hyperactivity Disorder (ADHD). NICHES integrates complementary in vitro, in vivo, and human clinical studies to identify how epigenetic changes caused by developmental ETS exposure are expressed in the brain and how they are associated with neurobehavioral dysfunction in children. We will determine if these changes are also detectable in the blood as part of an effort to discern an epigenetic signature of developmental ETS exposure. Our Community Outreach and Translation Core (COTC) will integrate efforts with the 3 research projects (P1-P3) to develop educational tools aimed at smoking prevention to improve children's health. Our overall specific aims are: 1) To define relevant epigenomic-transcriptomic changes induced by nicotine exposure. We will use a rodent model (P2) to define related epigenomic-transcriptomic changes induced by nicotine exposure in brain and blood (P3), and extend these results through leveraging our pre-existing longitudinal human cohort of mother-infant pairs to quantitatively test the relationship between ETS and DNA methylation (P1, P3). 2) Examine the effect of exposure timing on outcome and epigenetic effects. We will test prenatal vs. postnatal exposure on behavioral phenotypes in rodents (P2) and humans (PI). Mechanistic studies of neuronal differentiation and function in vitro (P2) will be related to DNA methylation (P3) in mediating observed phenotypes or disordered neurodifferentiation, and potential remediating effects of one-carbon pathway donors and antioxidants will be explored (P2); 3) Determine if methylation mediates the relationship between ETS exposure and ADI-ID-related neurobehaviors. We will define the potential mediating effect of DNA methylation (P3) on the relationship between ETS exposure and neurobehavioral phenotypes in humans (P1) and rodents (P2); and 4) Train multidisciplinary researchers at all levels to impact environmental health sciences (P1-P3 and COTC). NICHES expands existing collaborations and brings in new multidisciplinary scientists and educators to uncover epigenetic mechanisms that underlie ETS effects on neurocognitive impairments in children including ADHD. Our highly interactive projects and integrated COTC, supported by the Administrative Core, has tremendous potential to enable development of improved clinical interventions to prevent, reverse, or ameliorate ETS effects to benefit children's health.


Journal Articles: 24 Displayed | Download in RIS Format

Other center views: All 79 publications 27 publications in selected types All 24 journal articles
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Journal Article Fuemmeler BF, Wang L, Iversen ES, Maguire R, Murphy SK, Hoyo C. Association between prepregnancy body mass index and gestational weight gain with size, tempo, and velocity of infant growth: analysis of the Newborn Epigenetic Study cohort. Childhood Obesity 2016;12(3):210-218. R835437 (2015)
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  • Journal Article Hall BJ, Cauley M, Burke D, Kiany A, Slotkin TA, Levin ED. Cognitive and behavioral impairments evoked by low-level exposure to tobacco smoke components: comparison with nicotine alone. Toxicological Sciences 2016;151(2):236-244. R835437 (2015)
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  • Journal Article King KE, Kane JB, Scarbrough P, Hoyo C, Murphy SK. Neighborhood and family environment of expectant mothers may influence prenatal programming of adult cancer risk: discussion and an illustrative DNA methylation example. Biodemography and Social Biology 2016;62(1):87-104. R835437 (2015)
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  • Journal Article Levin ED. Learning about cognition risk with the radial-arm maze in the developmental neurotoxicology battery. Neurotoxicology and Teratology 2015;52(Pt A):88-92. R835437 (2014)
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  • Journal Article Murphy SK, Erginer E, Huang Z, Visco Z, Hoyo C. Genotype-epigenotype interaction at the IGF2 DMR. Genes 2015;6(3):777-789. R835437 (2014)
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  • Journal Article Nye MD, Fry RC, Hoyo C, Murphy SK. Investigating epigenetic effects of prenatal exposure to toxic metals in newborns: challenges and benefits. Medical Epigenetics 2014;2(1):53-59. R835437 (2013)
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  • Journal Article Nye MD, Hoyo C, Murphy SK. In vitro lead exposure changes DNA methylation and expression of IGF2 and PEG1/MEST. Toxicology In Vitro 2015;29(3):544-550. R835437 (2014)
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  • Journal Article Nye MD, King KE, Darrah TH, Maguire R, Jima DD, Huang Z, Mendez MA, Fry RC, Jirtle RL, Murphy SK, Hoyo C. Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort. Environmental Epigenetics 2016;2(1):1-8. R835437 (2015)
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  • Journal Article Slotkin TA, Card J, Seidler FJ. Adverse benzo[a]pyrene effects on neurodifferentiation are altered by other neurotoxicant coexposures: interactions with dexamethasone, chlorpyrifos, or nicotine in PC12 cells. Environmental Health Perspectives 2013;121(7):825-831. R835437 (2013)
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  • Journal Article Slotkin TA, Card J, Seidler FJ. Nicotine administration in adolescence reprograms the subsequent response to nicotine treatment and withdrawal in adulthood: sex-selective effects on cerebrocortical serotonergic function. Brain Research Bulletin 2014;102:1-8. R835437 (2014)
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  • Journal Article Slotkin TA, Card J, Stadler A, Levin ED, Seidler FJ. Effects of tobacco smoke on PC12 cell neurodifferentiation are distinct from those of nicotine or benzo[a]pyrene. Neurotoxicology and Teratology 2014;43:19-24. R835437 (2013)
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  • Journal Article Slotkin TA, Skavicus S, Card J, Levin ED, Seidler FJ. Amelioration strategies fail to prevent tobacco smoke effects on neurodifferentiation: nicotinic receptor blockade, antioxidants, methyl donors. Toxicology 2015;333:63-75. R835437 (2014)
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  • Journal Article Slotkin TA, Skavicus S, Card J, Stadler A, Levin ED, Seidler FJ. Developmental neurotoxicity of tobacco smoke directed toward cholinergic and serotonergic systems: more than just nicotine. Toxicological Sciences 2015;147(1):178-189. R835437 (2014)
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  • Journal Article Slotkin TA, Stadler A, Skavicus S, Seidler FJ. Adolescents and adults differ in the immediate and long-term impact of nicotine administration and withdrawal on cardiac norepinephrine. Brain Research Bulletin 2016;122:71-75. R835437 (2015)
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  • Journal Article Smeester L, Yosim AE, Nye MD, Hoyo C, Murphy SK, Fry RC. Imprinted genes and the environment: links to the toxic metals arsenic, cadmium, lead and mercury. Genes 2014;5(2):477-496. R835437 (2014)
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  • Journal Article Soubry A, Hoyo C, Jirtle RL, Murphy SK. A paternal environmental legacy: evidence for epigenetic inheritance through the male germ line. BioEssays 2014;36(4):359-371. R835437 (2013)
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  • Journal Article Vidal AC, Benjamin Neelon SE, Liu Y, Tuli AM, Fuemmeler BF, Hoyo C, Murtha AP, Huang Z, Schildkraut J, Overcash F, Kurtzberg J, Jirtle RL, Iversen ES, Murphy SK. Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans. Genetics and Epigenetics 2014;6:37-44. R835437 (2014)
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  • Journal Article Lee, W.-C., Shen, L., Catalano, P.J., Mickley, L.J., and Koutrakis, P. (2017). Effects of Future Temperature Change on PM2.5 Infiltration in the Greater Boston Area. Atmospheric Environment 150, 98-105. R835437 (2016)
    R834798 (Final)
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    Journal Article Slotkin, T.A., Stadler, A., Skavicus, S., Card, J., Ruff, J., Levin, E.D., Seidler, F.J. 2016. Is there a critical period for the developmental neurotoxicity of low-level tobacco smoke exposure? Toxicological Sciences. DOW:10.1093. R835437 (2016)
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    Journal Article Slotkin, T.A., Skavicus, S., Card, J., Levin, E.D., Seidler, F.J. 2016. Diverse Neurotoxicants Target the Differentiation of Embryonic Neural Stem Cells into Neuronal and Glial Phenotypes. Toxicology. 372 42-51. R835437 (2016)
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    Journal Article Carrie V. Breton, Carmen J. Marsit, Elaine Faustman, Kari Nadeau, Jaclyn M. Goodrich, Dana C. Dolinoy, Julie Herbstman, Nina Holland, Janine M. LaSalle, Rebecca Schmidt, Paul Yousefi, Frederica Perera, Bonnie R. Joubert, Joseph Wiemels, Michele Taylor, Ivana V. Yang, Rui Chen, Kinjal M. Hew, Deborah M. Hussey Freeland, Rachel Miller, and Susan K. Murphy. 2017. Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children’s Environmental Health Studies:The Children’s Environmental Health and Disease Prevention Research Center’s Epigenetics Working Group. Environmental Health Perspectives. 2017:125(4) 511-526. R835437 (2016)
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    Journal Article Levin ED and Y Abreu-Villaça. Developmental neurotoxicity of nicotine and tobacco. In Handbook of Developmental Neurotoxicology, (C. Wang, M. Paule, and W. Slikker, Jr. eds.), Academic Press, San Diego, 2017. R835437 (2016)
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    Journal Article Fleisch, A.F., Kloog, I., Luttmann-Gibson, H., Gold, D.R., Oken, E., and Schwartz, J.D. (2016). Air Pollution Exposure and Gestational Diabetes Mellitus Among Pregnant Women in Massachusetts:a Cohort Study. Environmental Health 15, 1-9. R835437 (2016)
    R834798 (Final)
    R834798C005 (Final)
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    Journal Article Breton, C.V., Marsit, C.J., Faustman, E., Nadeau, K., Goodrich, J.M., Dolinoy, D.C., Herbstman, J., Holland, N., LaSalle, J.M., Schmidt, R., Yousefi, P., Perera, F., Joubert, B.R., Wiemels, J., Taylor, M., Yang, I.V., Chen, R., Hew, K.M., Hussey Freeland, D.M.,Miller, R. and S.K. Murphy. 2016. Small Magnitude Effect Sizes in Epigenetic Endpoints are Important in Children's Environmental Health Studies:The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environmental Health Perspectives (in press) DOI:10.1289/EHP595. R835437 (2016)
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    Progress and Final Reports:

    2013 Progress Report
    2014 Progress Report
    2015 Progress Report
    2016 Progress Report