Grantee Research Project Results
Neurodevelopment and Improving Children's Health following EtS exposure (NICHES)
EPA Grant Number: R835437Center: 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: Hahn, Intaek
Project Period: June 1, 2013 through May 31, 2018 (Extended to May 31, 2019)
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 , Human 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: 77 Displayed | Download in RIS Format
Other center views: | All 117 publications | 39 publications in selected types | All 33 journal articles |
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Cauley M, BJ Hall BJ, Burke DA, Lee AK, Schwartz-Bloom R, Levin ED. Locomotor hyperactivity caused by developmental exposure to low dose tobacco smoke extract in rats. In: Society for Neuroscience Annual Meeting Program and Abstracts, Washington, DC, November 15-19, 2014, Abstract 145.19. |
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Cauley M, BJ. Hall, Y Abreu-Villaça, S Junad, H White, A Kiany and ED Levin. Critical windows of tobacco smoke chemical exposure causing long-term behavioral effects in rats. NIEHS Environmental Health Science FEST, December 6-8, 2016, Durham, NC. |
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Hall BJ, Cauley M, Burke DA, Levin ED. Neurobehavioral consequences of gestational exposure to a low dose of tobacco smoke extract in rats. Neurotoxicology and Teratology 2014;43:96-97. |
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Hall BJ, Cauley M, Burke DA, Kiany A and Levin ED. Early developmental exposure of rats to low dose tobacco smoke extract or nicotine modeling second hand smoke produce long-term behavioral dysfunction. The Toxicologist 2015;144:(1):384. |
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Hall BJ, Cauley M, Kiany A, Burke DA, Levin ED. Low dose tobacco smoke extract exposure during development causes long-term behavioral dysfunction in rats. Neurotoxicology and Teratology 2015;49:121-122. |
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Hall BJ, Cauley M, Kiany A, Burke DA, Levin ED. Low dose tobacco smoke extract exposure during development causes long-term behavioral dysfunction in rats. Neurotoxicology and Teratology 2015;49:121-122. |
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Hall BJ, Cauley M, White HJ, Junaid S, Kiany A, Abreu-Villaca Y, Levin ED. Neurobehavioral effects of exposure to tobacco smoke extract in rats during critical windows of gestational development. The Toxicologist: Supplement to Toxicological Sciences 2016;150(1):38 (Abstract 1164). |
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Hawkey A, Junaid S, Yao L, Spiera Z, Cauley M, Wells CN, White H, Levin ED. Gestational exposure of rats to low concentrations of tobacco smoke components, nicotine and benzo-a-pyrene, diminishes normal sex-differences in behavior. In: Abstracts from the Society for Neuroscience Annual Meeting, Washington, DC, November 11-15, 2017 (Abstract QQ18). |
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Hawkey A, Junaid S, Yao L, White H, Cauley M, Levin ED. Persisting behavioral effects of gestational exposure of rats to nicotine and benzo-a-pyrene. The Toxicologist 2018;162(1):99 (Abstract #1413). |
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Kollins S, Levin E, Price T, Murphy SK. Delta-9-Tetrahydrocannabinol exposure alters sperm methylation profiles: concurrent results from humans and rats. Neuropsychopharmacology 2017;43:S642-S643 (Abstract W265). |
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Levin ED. Assessment of working memory and reversal learning in regulatory studies. Neurotoxicology and Teratology 2013;37:83-84. |
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Levin ED. Long-term behavioral dysfunction caused by early developmental exposure to low dose tobacco smoke extract or nicotine in rats. In: Endocrine Society's Poster Presentation Abstract Book: Environmental Stressors in Disease and Implications for Human Health, 4th Annual Prenatal Programming and Toxicity Meeting (PPTox IV), Boston, MA October 26-29, 2014, p. 97. |
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Levin ED. Developmental neurotoxicity: sex differences in toxic effects and toxic effects on sex differences. Toxicology Letters 2017;280;(Suppl 1):S150. |
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Levin ED. Neurodevelopmental toxicity of tobacco smoke and nicotine. Neurotoxicology and Teratology 2017;61:153 (DNTS 34). |
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Levin ED, Cauley M, Hall B, Abreu-Villaca Y, Junaid S, White H, Kiany A. Prenatal exposure to tobacco smoke extract and some of its constituents in rats cause persisting neurobehavioral effects in the offspring. Neurotoxicology and Teratology 2017;61:156 (Abstract DNTS 44). |
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Levin ED, Cauley M, Hall BJ, Abreu-Villaça Y, Junaid S, White H, Hawkey A. Transgenerational neurobehavioral toxicity of nicotine and tobacco exposure in rats. In: Abstract Book for the Annual Meeting of the Society for Research on Nicotine and Tobacco, Baltimore, MD, February 21-24, 2018, p. 30, (Abstract Sym21A). |
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Levin E, Hall B, Cauley M. Neurotoxic effects on attention deficit and hyperactivity in rodent models. Neurotoxicology and Teratology 2015;49:116 (Abstract NTX51). |
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Murphy SK, Keyhan S, Guo L, Tomins K,Taylor M, Joglekar R, Huang Z, Grenier C, Liao Y, Massarsky A,Soubry A, Lea A, Burke EE, Cauley M, Hall BJ, Lucas JE, Hoyo C, Di Giulio RT, Levin ED, Price TM. Environmental influence on preconceptional and gestational DNA methylation profiles. Environmental and Molecular Mutagenesis 2016;57(Suppl 1):S39 (Abstract S2). |
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Murphy SK, Schrott R, Visco Z, Huang Z, Grenier C, Mitchell J, Schechter J, Lucas J, Levin ED, Price T, Kollins SH. Environment and gametic epigenetic reprogramming. Environmental and Molecular Mutagenesis 2017;58(Suppl 1):S28 (Abstract S15). |
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Schechter, J. Secondhand Smoke Exposure in Pregnant Women:Analysis of the Newborn Epigenetic Study Cohort. Society for Research on Nicotine and Tobacco, 2017 Annual Meeting, Florence, Italy. |
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Seidler FJ, Levin ED, Slotkin TA. Comparative developmental neurotoxicity of tobacco smoke and nicotine, in vivo and in vitro. The Toxicologist: Supplement to Toxicological Sciences 2016;150(1):38 (Abstract 1163). |
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Tindula G, Murphy S, Grenier C, Huang Z, Huen K, Escudero-Fung M, Bradman A, Eskenazi B, Hoyo C, Holland N. DNA methylation of imprinted genes in Mexican-American newborn children with prenatal phthalate exposure. Environmental and Molecular Mutagenesis 2017;58(Suppl 1):S63 (Abstract P28). |
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Schechter, J., Davis, N. O., Fuemmeler, B., Murphy, S., Hoyo, C., & Kollins, S. Early Developmental Risk Factors for ADHD Symptoms in Young Children. Paper presented at the APSARD, Washington, D.C. January 13-15, 2017. Poster selected for poster tour and received honorable mention. |
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Taylor, M. Association of Prenatal Environmental Tobacco Smoke Exposure and Increased Methylation of the Imprinted Genes MEG3 and MEG3-IG. National Institute of Environmental Health Sciences FEST, Durham, NC. December 6-8, 2016. |
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Levin, E.D. Critical windows of tobacco smoke chemical exposure causing long-term behavioral effects in rates. National Institute of Environmental Health Sciences FEST, Durham, NC. December 6-8, 2016. |
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Fuemmeler, B. Effects of prenatal tobacco smoke exposure on attention regulation and language acquisition in early childhood. National Institute of Environmental Health Sciences FEST, Durham, NC. December 6-8, 2016. |
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Joglekar R, Grenier C, Liao Y, Murphy SK. Elevated cord blood cotinine levels associated with increased DNA methylation at the human metastable epiallele PAX8, 2016 NCSOT Annual Meeting, Research Triangle Park, NC, October 2016. |
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Joglekar R, Grenier C, Liao Y, Murphy SK. Elevated cord blood cotinine levels associated with increased DNA methylation at the human metastable epiallele PAX8, NIEHS Environmental Health Science Fest December 6-8, 2016, Durham, NC. |
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Joglekar R, Grenier C, Liao Y, Murphy SK. Elevated cord blood cotinine levels associated with increased DNA methylation at the human metastable epiallele PAX8, ToxicoEpigenetics Conference 2016, Tysons, VA, November 2016. |
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Maguire, R. First trimester blood cadmium and lead levels are associated with cardiometabolic risk markers in children. National Institute of Environmental Health Sciences FEST, Durham, NC. December 6-8, 2016. |
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Cauley M, BJ. Hall, Y Abreu-Villaça, S Junad, H White, A Kiany and ED Levin. Low dose exposure to tobacco smoke chemicals during premating, early or late gestation in female rats cause persisting neurobehavioral effects in the offspring. Society of Toxicology, March 12-16, 2017, Baltimore, MD. |
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Schechter, J. Independent and Interactive Effects of Prenatal Cotinine Exposure and Maternal Depression on Birthweight. National Institute of Environmental Health Sciences FEST, Durham, NC. December 6-8, 2016. |
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Murphy SK, Tomins K, Massarsky A, Guo L, Hall BJ, Cauley M, Schrott R, Huang Z, Lea A, Burke EE, Lucas J, Di Giulio R, Levin ED. Marked DNA methylation changes in rat and zebrafish sperm following tobacco smoke exposure. Society of Toxicology, March 12-16, 2017, Baltimore, MD. |
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House, J. Maternal Nutrition and Early Childhood Behavioral Outcomes in NEST. National Institute of Environmental Health Sciences FEST, Durham, NC. December 6-8, 2016. |
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Levin ED, M Cauley, A Hawkey, C Wells, S Junaid, L Yao and Z Spiera. Persisting effects of separate and combined nicotine and benzo-a-pyrene exposure during gestation on motor, emotional and cognitive functions in rats. International Neurotoxicology Association and Neurotoxicity Society Joint Meeting, May 20-23, 2017, Florianopolis, Brazil. |
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Lunsford-Avery, J.R., Schechter, J., Ornstein Davis, N., Mitchell, J.T., Fuemmeler, B. F., & Kollins, S.H. Actigraphically-Measured Sleep Disturbances and Impaired Executive Functioning in a Community Sample of Young Children. Poster abstract at the APSARD Annual Meeting, Washington, D.C. January 13-15, 2017. |
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Hall BJ, Y Abreu-Villaça, M Cauley, S Juniad, H White, A Kiany and ED Levin. Sex differences in ventral hippocampal muscarinic acetylcholine antagonist scopolamine effects on spatial memory in rats. Society for Neurosciences, Annual Meeting, San Diego, CA, November 12-16, 2016. |
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Barry, C. Using mobile and digital technology to improve cohort management in the Duke NICHES cohort. National Institute of Environmental Health Sciences FEST, Durham, NC. December 6-8, 2016. |
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Levin ED. Developmental toxicology and children’s environmental health. In: Landrigan PJ, Etzel RA, eds. Textbook of Children’s Environmental Health. New York, NY: Oxford University Press, December 13, 2013, Chapter 9, pp. 83-88. |
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Levin ED. Chronic nicotine effects on memory and nicotine self-administration: age of exposure is key. In: Aschner M, Costa LG, eds. Advances in Neurotoxicology, Volume 2, San Diego, CA: Academic Press, 2018, Chapter 6, pp. 189-196. |
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Levin ED, Abreu-Villaca Y. Developmental neurotoxicity of nicotine and tobacco. In: Slikker Jr. W, Paule MG,Wang C, eds. Handbook of Developmental Neurotoxicology, 2nd Edition, San Diego, CA: Academic Press, 2018, Chapter 39, pp. 439-452. |
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Moylan CA, Murphy SK. DNA methylation: basic principles. In: Tollefsbol T, ed. Medical Epigenetics. London: Elsevier, Academic Press, 2016, Chapter 2, pp. 11-31. |
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Taylor MM, Murphy SK. Systems biology and the epigenome. In: Fry R, ed. Systems Biology in Toxicology and Environmental Health. Amsterdam: Elsevier, Academic Press, 2015, Chapter 3, pp. 43-56. |
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Levin ED, 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, 439-452 pp |
R835437 (2016) R831711 (Final) |
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Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, Herbstman J, Holland N, LaSalle JM, Schmidt R, Yousefi P, Perera F, Joubert BR, Wiemels J, Taylor M, Yang IV, Chen R, Hew KM, Hussey Freeland DM, Miller R, Murphy SK. 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. |
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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 2017; 125(4):511-526. |
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Cauley M, Hall BJ, Abreu-Villaca Y, Junaid S, White H, Kiany A, Slotkin TA, Levin ED. Critical developmental periods for effects of low-level tobacco smoke exposure on behavioral performance. Neurotoxicology 2018;68:81-87. |
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Fleisch AF, Kloog I, Luttmann-Gibson H, Gold DR, Oken E, and Schwartz JD. Air Pollution Exposure and Gestational Diabetes Mellitus Among Pregnant Women in Massachusetts:a Cohort Study. Environmental Health 2016; 15:40-48. |
R835437 (2016) R834798 (Final) R834798C005 (Final) |
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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. |
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Fuemmeler BF, Lee CT, Soubry A, Iversen ES, Huang Z, Murtha AP, Schildkraut JP, Jirtle RL, Murphy SK, Hoyo C. DNA methylation of regulatory regions of imprinted genes at birth and its relation to infant temperament. Genetics and Epigenetics 2016;8:59-67. |
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Fuemmeler B, Glasgow T, Schechhter J, Maguire R, Sheng Y, Bidopia T, Barsell D, Ksinan A, Zhang J, Lin Y, Hoyo C, Murphy S, Qin J, Wang X, Kollins S. Prenatal and Childhood Smoke Exposure Associations with Cognition, Language, and Attention-Deficit/Hyperactivity Disorder. JOURNAL OF PEDIATRICS 2023;256:77 |
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Gao L, Liu X, Millstein J, Siegmund KD, Dubeau L, Maguire RL, Zhang JJ, Fuemmeler BF, Kollins SH, Hoyo C, Murphy SK, Breton CV. Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes. Clinical Epigenetics 2018;10(1):98 (11 pp.). |
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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. |
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Hall BJ, Abreu-Villaca Y, Cauley M, Junaid S, White H, Kiany A, Levin ED. The ventral hippocampal muscarinic cholinergic system plays a key role in sexual dimorphisms of spatial working memory in rats. Neuropharmacology 2017;117:106-113. |
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Hoffman K, Butt C, Webster T, Preston E, Hammel S, Makey C, Lorenzo A, Cooper E, Carignan C, Meeker S, Price T, Hoyo C, Mendelsohn E, Congleton J, Daniels J, Stapleton H. Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States. ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS 2017;4(3):112-118. |
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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. |
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Lee W-C, Shen L, Catalano PJ, Mickley LJ, and Koutrakis P. Effects of Future Temperature Change on PM2.5 Infiltration in the Greater Boston Area. Atmospheric Environment 2017;150:98-105. |
R835437 (2016) R834798 (Final) R835755 (2016) |
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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. |
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Murphy SK, Erginer E, Huang Z, Visco Z, Hoyo C. Genotype-epigenotype interaction at the IGF2 DMR. Genes 2015;6(3):777-789. |
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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. |
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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. |
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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. |
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Schechter JC, Kollins SH. Prenatal smoke exposure and ADHD: advancing the field. Pediatrics 2017;139(2):e20163481 (2 pp.). |
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Schechter JC, Fuemmeler, BF, Hoyo C, Murphy SK, Zhang JJ, Kollins SH. Impact of smoking ban on passive smoke exposure in pregnant non-smokers: using cotinine as a biomarker of exposure. International Journal of Environmental Research and Public Health 2018;15(1):E83 (16 pp.). |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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Slotkin TA, Skavicus S, Card J, Levin ED, Seidler FJ. Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes. Toxicology 2016;372:42-51. |
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Slotkin TA, Stadler A, Skavicus S, Card J, Ruff J, Levin ED, Seidler FJ. Is there a critical period for the developmental neurotoxicity of low-level tobacco smoke exposure? Toxicological Sciences 2017;155(1):75-84. |
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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. |
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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. |
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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. |
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Tindula G, Murphy SK, Grenier C, Huang Z, Huen K, Escudero-Fung M, Bradman A, Eskenazi B, Hoyo C, Holland N. DNA methylation of imprinted genes in Mexican-American newborn children with prenatal phthalate exposure. Epigenomics 2018;10(7):1011-1026. |
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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. |
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Progress and Final Reports:
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- Final Report
- 2017 Progress Report
- 2016 Progress Report
- 2015 Progress Report
- 2014 Progress Report
- 2013 Progress Report
33 journal articles for this center