Final Report: The UC Davis Center for Children's Environmental Health and Disease Prevention

EPA Grant Number: R835432
Center: UC Davis Center for Children's Environmental Health and Disease Prevention
Center Director: Van de Water, Judith
Title: The UC Davis Center for Children's Environmental Health and Disease Prevention
Investigators: Van de Water, Judith , Bennett, Deborah H. , Lein, Pamela J , LaSalle, Janine M , Pessah, Isaac N. , Puschner, Birgit , Walker, Cheryl , Sharp, Frank , Hertz-Picciotto, Irva , Ritchie, Marylyn , Hagerman, Paul , Ashwood, Paul , Schmidt, Rebecca , Hansen, Robin , Lin, Yanping
Institution: University of California - Davis
EPA Project Officer: Nolt-Helms, Cynthia
Project Period: June 1, 2013 through May 31, 2018 (Extended to May 31, 2019)
Project Amount: $3,827,820
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 overarching aims of the UC Davis Center for Children’s Environmental Health are:

(1) Leverage our existing studies and biobanks for specimens to expand our research and capitalize upon the Center’s research findings to date. We will take advantage of our numerous resources from the CHARGE study, as well as the epidemiological and clinical studies involving prospective parents, pregnant women, and children from the ongoing MARBLES study — both of which grew out of previous years of CCEH funding;

(2) Build upon our novel findings of calcium dysregulation in cultured neurons and immune cells in the context of understanding the epigenetic effects and ramifications of toxicant exposure on gene pathways and immune function;

(3) Develop and apply new biomarkers of autism risk, through analysis of gestational immune dysfunction, genetic susceptibility, and environmental exposures, to best characterize the potential health effects at various life stages and predict longer-term clinical and behavioral consequences;

(4) Train new investigators, including pre- and post-doctoral fellows and junior faculty, to address emerging issues in children’s environmental health with cross-cutting technologies and integrated multidisciplinary approach; and

(5) Expand the successful Community Outreach and Translation Core to continue the active engagement of our ASD families, as well as the California Department of Health Services and the broader cross-cultural community in the research process, and the translation and application of our research findings.

Summary/Accomplishments (Outputs/Outcomes):

Project 1

In utero pyrethroid pesticide and neurodevelopmental outcomes from 6 - 36 months of age in the MARBLES longitudinal cohort
Background/Aim: Little is known about the effects of in utero pyrethroid pesticide exposure on child development. We assessed the relationships between pyrethroid pregnancy exposure and (1) autism spectrum disorders (ASD) or non-typical development (NT) at 3 years, (2) child cognition from 6 – 36 months on the Mullen Scales of Early Learning (MSEL).

Methods: Participants were mother-child pairs (n=215) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort. Because family recurrence risks in siblings are about 20%, the MARBLES study enrolls pregnant women who already had a child with ASD. Children were clinically assessed at 3 years and classified into 3 diagnostic categories: ASD, NT, or typically developing (TD). Repeated maternal second and third trimester urine samples were analyzed for pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA). We calculated weights for use in regression models based on number of urine samples per woman and the intraclass correlation. Multinomial logistic regression was used to obtain risk ratios (RR) for pregnancy average 3-PBA concentrations relative to child’s diagnosis. Linear regression models were used to investigate average in utero 3-PBA concentrations and Mullen Scales of Early Learning (MSEL) scores.

Results: The median SG-adjusted 3-PBA concentration of all samples was 1.46 ng/ml. Adjusting for specific gravity, maternal pre-pregnancy BMI, prenatal vitamin use, birth year, homeownership, and TCPy (a metabolite of organophosphate pesticides) pregnancy concentrations, prenatal 3-PBA concentrations were weakly associated with higher risk of ASD (RR 1.33, 95% CI: 0.89 - 1.96) and compared to TD children. After applying weights to 3-PBA concentrations and adjusting for SG, maternal BMI, prenatal vitamin use, birth year, homeownership and TCPy pregnancy concentrations, we found significantly lower MSEL Gross Motor (β= - 1.20, p=0.05) scores at 6 months. In utero pyrethroid pesticide exposures showed a suggestive association with lower scores on both the MSEL composite (β = -1.51, p= 0.07) and fine motor (β = -1.01, p=0.09) at 6 months.

Conclusions: This may be the first study to assess a biomarker of pyrethroid exposure, based on multiple—up to 6—urine samples, from the 2nd and 3rd trimesters of pregnancy in relation to ASD and child cognitive development from 6 - 36 months. These findings suggest in utero 3-PBA concentrations are not strongly related to a diagnosis of ASD but may impact cognitive development in early infancy. The role of post-natal exposures has yet to be assessed with regard to post-infancy outcomes. With widespread use of pyrethroid pesticides further investigations of neurodevelopment in childhood are warranted.

Prenatal pesticide exposure, child gene expression, and neurodevelopmental outcomes in the MARBLES longitudinal cohort study

Background: Chlorpyrifos and pyrethroid pesticides are widely used, and prenatal exposures may increase the risk for adverse neurodevelopmental outcomes including autism spectrum disorder (ASD). Genetic factors may increase susceptibility to pesticide exposure. Gene environment interactions are of particular interest due to the complex etiology of ASD.

Aims: To assess associations between prenatal pesticide exposures and child gene expression at birth in a cohort at high risk for developing autism or other developmental delays, both overall and within diagnostic groups.

Methods: Participants (n=91) were from the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) longitudinal cohort study in northern California. We measured pyrethroid metabolite 3-PBA (3-phenoxybenzoic acid) and chlorpyrifos metabolite TCPy (3,5,6-trichloro-2-pyridinol) from multiple maternal urine samples collected during pregnancy, and gene expression from three selected genes of interest (SFRP2, VANGL2, PON1) in child serum umbilical cord samples from delivery. We assessed associations between in utero pesticide exposures and child gene expression, both overall and stratified by child’s 3-year clinical outcome of ASD, non-typical development or typical development with the use of linear regression models.

Results: After adjusting for birth year, prenatal vitamin use and child’s race/ethnicity we found pregnancy urinary TCPy concentrations were marginally associated with VANGL2 expression (β= 0.03, p=0.082), but 3-PBA concentrations were not significantly associated with expression for any of the three selected genes. After stratifying by child’s clinical outcome we observed a significant association between pregnancy TCPy concentrations and lower PON1 expression (β = -0.07, p=0.002) within the ASD group. Within this same group, pregnancy 3-PBA concentrations were weakly associated with higher VANGL2 expression (β = 0.11, p=0.119) and lower SFRP2 expression (β = -0.37, p=0.116). Pregnancy 3-PBA concentrations were also weakly associated with higher SFRP2 expression (β= 0.11, p=0.112) among children with typical development.

Conclusions: This study may provide the first evidence for the influence of prenatal pesticide exposures on expression of several genes that are known to influence risk for ASD. This study used gold-standard assessments of ASD and biomarkers of in utero pesticide exposure. Gene expression was measured at birth, which ultimately could prove useful for a pre-clinical biomarker of elevated risk for ASD. These results are from a high-risk population and small sample. Further investigation of the underlying genetic mechanisms for the differences we observed in gene expression should be conducted in a larger sample.

Exposome-wide association study (EWAS) identifies link between pregnancy anxiety and various autism spectrum traits.

Autism spectrum disorder (ASD) is a complex trait that is characterized by atypical social and behavioral development and can be accompanied by altered intellectual development. There are a number of studies showing links between environmental exposures and increased risk in developmental disorders, including autism. We used environmental exposure data from Childhood Autism Risks from Genetics and the Environment (CHARGE), a population-based study of children aged 2-5 years, in three categories: ASD, Developmental Delay (DD), and General Population/Typical Development (TD). We designed a multi-step analysis, in which we first performed an exposome-wide association study (EWAS) to identify factors predictive of ASD. Then, we tested the variable most strongly associated with ASD for associations with 56 clinical assessment variables and 11 child measurement variables recorded on CHARGE participants to further explain its link with the exposure. Using an EWAS approach, we evaluated 874 demographic, maternal health, maternal lifestyle, chemical exposure, residential, and other pregnancy variables from 1286 participants (778 ASD, 508 TD) using logistic regression, adjusting for sex, age, and race. We found six exposure variables that met the Bonferroni significance threshold (for alpha=0.05). The association with maternal nervousness or anxiety during pregnancy (maternal health) was the most significant (p-value = 4.05 x 10-6, OR= 2.21 [1.56, 3.14]). A variety of previous studies have demonstrated that prenatal anxiety or stress is linked to developmental disorders and autism spectrum traits. Subsequently, we found 18 clinical assessment variables significantly associated with maternal nervousness or anxiety using a multi-phenotype approach similar to what is used in phenome-wide association studies, with “Irritability” in children being the most significant association (p-value = 1.82 x 10-8 and beta = 4.20). Other clinical assessment variables significantly associated with pregnancy nervousness or anxiety were hyperactivity, inattention, stereotypy, lethargy, and novel associations with several developmental quotient variables. These findings highlight the potential links between maternal mental health during pregnancy and neurobehavioral developmental in children. In the future, we will investigate the combined effect of these exposure variables on autism spectrum traits.

Project 2

Whole genome sequencing and whole genome bisulfite sequencing on 92 MARBLES cord blood samples were successfully completed and several manuscripts are in preparation. The intellectual interactions with in the CCEH led to a number of new collaborations on gene by environmental interactions at the epigenetic interface, including neuroimmune and PCB interactions.

Project 3

1. Exposure to Persistent Organic Flame Retardants PBDE elicits differential Immune Responses in Peripheral Blood Mononuclear Cells in Children with ASD:

Children with autism (ASD) have immune dysregulation that often correlates with behavioral deficits. Test the hypothesis of associations between plasma PBDE and immune cell function in children with and without ASD. Plasma from children enrolled in the CHARGE (CHildhood Autism Risks from Genetics and the Environment) with (ASD; n=38) and without (TD; n=60) ASD diagnosis were analyzed for 11 major PBDE congeners using GC-tandem mass spectrometry. Basal and activated cytokine/chemokine secretion was measured from peripheral blood mononuclear cells (PBMC) supernatants, with and without ex vivo BDE-49. Total body burden (∑PBDE12) and individual congener levels were correlated with T cell cytokine/chemokine production. ∑PBDE12 did not differ between diagnostic groups., but ∑PBDE12 correlated with suppressed immune responses, and baseline T cell functions were more profoundly affected (lower IL-2, IL-13 and IFN-γ) in ASD. Higher ∑PBDE12 were negatively correlated with adaptive T-cell cytokines IL-2, IL-13, IL-17 and IL-10 after activation of PBMC. Baseline production of T cell IL-2 and IFN-γ were negatively impacted by several individual BDE congeners in ASD compared to TD, especially for BDE-49 (p=0.001). ASD PBMC exposed to 50 nM BDE-49 showed higher inflammatory cytokines IL-6, TNF-a, IL-1b, and the chemokines MIP-1α and MCP-1 in ASD cases (p<0.05). Increased IL-6 (p=0.01) and GM-CSF (p=0.03) following pre-treatment with 250 nM BDE-49 was positively correlated with higher body burden of BDE-49, but not BDE-47 or BDE-95. Conclusion: Despite similar body burdens of PBDEs in ASD and TD, PBDE exposures differentially impact immune responsiveness in ASD with little or no impact on TD children, suggesting an underlying association between susceptibility to PBDEs and immune anomalies in ASD.

2. Increased production of IL-17 in children with autism spectrum disorders and co-morbid asthma

Inflammation and asthma have both been reported in some children with autism spectrum disorder (ASD). To further assess this connection, peripheral immune cells isolated from young children with ASD and typically developing (TD) controls and the production of cytokines IL-17, -13, and -4 assessed following ex vivo mitogen stimulation. Notably, IL-17 production was significantly higher following stimulation in ASD children compared to controls. Moreover, IL-17 was increased in ASD children with co-morbid asthma compared to controls with the same condition. In conclusion, children with ASD exhibited a differential response to T cell stimulation with elevated IL-17 production compared to controls.

3. A Mixture of Autism-Relevant Inflammatory Cytokines Activates Nuclear Factor-Kappa B and Alters Cell Viability and Synaptic Connectivity in a Human Neuronal Cell Line.

Working with Project 4, we completed studies screening the cytokine profiles derived from our studies of women whose blood was collected during pregnancy.

Maternal infection during pregnancy is associated with increased risk of autism, schizophrenia, and other neurodevelopmental disorders. Preclinical models have also demonstrated that elevated inflammatory cytokine levels in the maternal and fetal compartments following maternal immune activation lead to behavioral changes in the offspring. Cytokines, classically known as immune signaling molecules, serve important functions in brain development, and previous studies have demonstrated that cytokines can alter neurite outgrowth and synaptic connectivity in cultured rodent neurons. The Van de Water lab identified patterns of cytokines/chemokines that were associated with having a child with ASD + intellectual disability (ID) versus neurotypical and developmentally delayed children without ASD. In conjunction with the Lein lab (through a shared graduate student) we determined the effects the ASD cytokine mix on cell viability, neuronal apoptosis, neurite outgrowth, neurite retraction, and synaptogenesis in the human LUHMES neuronal cell line. We found that the cytokine profile associated with having a child with ASD +ID significantly modulated these endpoints in LUHMES cells. At concentrations that activated nuclear factor-kappa B (NF-κB) in LUHMES cells, ICM altered cytokine receptor expression, induced caspase-3/7 activity, and reduced synapse number. ICM also significantly altered measures of overall neurite outgrowth, but only at concentrations that also reduced cell viability. These results show that ICM activates NF-κB signaling in LUHMES cells and suggest that exposure to inflammatory cytokines promotes apoptosis and alters synaptic connectivity in developing neurons, two endpoints of relevance to neurodevelopmental disorders.

These data, which have significant implications for understanding the role of neuroimmune interactions in ASD, are currently accepted for publication in Molecular Psychiatry, a Nature journal.

Project 4

Project 4 has tested the hypothesis that CGG trinucleotide repeats in the FMRI gene, the most prevalent single gene disorder contributing to autism risk, influence susceptibility to non-dioxin-like (NDL) persistent organic pollutants (POPs) identified in Core 3 and pro-inflammatory cytokine profiles identified in Project 3 to predominate in plasma of women participating in the MARBLES study during pregnancy. Project 3 Co-PIs Pessah and Lein have coauthored >60 peer reviewed publications during the project period that are relevant to the original specific aims proposed for Project 4 of the UC Davis Center. Specifically, work in Project 4 has led to better understanding of the molecular and cellular mechanisms that contribute to susceptibility to neurodevelopmental disorders through interactions of two genetic loci (RYR1 and FMR1) and several high-priority halogenated persistent organic pollutants. The project has also provided important new information regarding the identity of emerging pollutants whose sources can be traced to both waste water treatment and marine natural products.

Conclusions:

Center investigators, students and staff met monthly throughout the life of the Center to present results, discuss progress and challenges. Center investigators presented key research results and challenges. The Center leadership continued oversee biobanking and resource sharing. The COTC expanded its outreach efforts and is working collaboratively with the UC Davis EHS Center.

The Administrative Core worked with project and core leaders and their unit grants management staff to update and align budgets, as well as distribute the federal and institutional matching funds in support of this program. The Core has organized ongoing monthly CCEH research meetings with rotating presentations provided by leaders from each of the center’s components. We have also continued to facilitate the Scientific Advisory Committee, which met for a final time, January 10, 2018. Lastly, the Core made multiple improvements to the Center’s biobank management and developed a new application and process for requesting specimens and data, as well as establishing an internal committee to coordinate oversight of the biobank.

The COTC continued to provide opportunities for Center researchers to share their research with different audiences. Center Director Judy Van de water, Project 2 co-leaders, Janine LaSalle and Rebecca Schmidt, along with Dr. Robin Hansen gave a panel presentation for parents at the UC Davis Child Development Center on current topics in prenatal gene-environment interactions and neurodevelopmental outcomes. Other panelists included a genetic counselor and a breastmilk nutrition researcher. The event was co-sponsored with the UC Davis Genome Center’s community engagement core. The COTC is also collaborating with the recently funded NIEHS P30 center COEC. The COTC and COEC have established an

environmental health sciences writing internship for the University Writing Program. Interns have written several articles for the CCEH and Core Center that have been published in the campus paper, the California Aggie, which has a Facebook reach of approximately 240,000.Also, this year a short documentary film about the CHARGE study was produced and released for public viewing. The video is available on the CCEH webpages and also on YouTube. Project TENDR also released a short documentary film, which premiered at the NIEHS FEST Film

Festival and is also available for viewing on the center website and YouTube. CCEH investigators continued to present their findings at major scientific conferences—IMFAR, SOT, Biophysical Society and others. Finally, Dr. Hertz-Picciotto from Project 1 and Project TENDR co-founder, has participated in state and federal legislative briefings on environmental impacts to neurodevelopment. Significant results from the Analytical Core suggest a positive association between PBDE exposure and gestational risk of autism. Concentrations of PBDEs in MARBLES women, who had a previous child with ASD, were higher compared to those in pregnant women at lower risk. We have evaluated the use of derivatization with dansyl chloride to analyze for 23 OH-PBDEs and OH-PCBs by LC/MS-MS analysis. We utilized plasma from the original MARBLES cohort (n=194) to apply and assess this methodology.


Journal Articles: 162 Displayed | Download in RIS Format

Other center views: All 165 publications 165 publications in selected types All 162 journal articles
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Journal Article Akins RS, Krakowiak P, Angkustsiri K, Hertz-Picciotto I, Hansen RL. Utilization patterns of conventional and complementary/alternative treatments in children with autism spectrum disorders and developmental disabilities in a population-based study. Journal of Developmental and Behavioral Pediatrics 2014;35(1):1-10. R835432 (2013)
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  • Journal Article Akintunde ME, Rose M, Krakowiak P, Heuer L, Ashwood P, Hansen R, Hertz-Picciotto I, Van de Water J. Increased production of IL-17 in children with autism spectrum disorders and co-morbid asthma. Journal of Neuroimmunology 2015;286:33-41. R835432 (2014)
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  • Journal Article Ariza J, Hurtado J, Rogers H, Ikeda R, Dill M, Steward C, Creary D, Van de Water J, Martinez-Cerdeno V. Maternal autoimmune antibodies alter the dendritic arbor and spine numbers in the infragranular layers of the cortex. PLoS One 2017;12(8):e0183443 (13 pp.). R835432 (2017)
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  • Journal Article Bal-Price A, Lein PJ, Keil KP, Sethi S, Shafer T, Barenys M, Fritsche E, Sachana M, Meek ME. Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity.NeuroToxicology 2016 May 17, doi:10.1016/j.neuro.2016.05.010 [Epub ahead of print]. R835432 (2015)
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  • Journal Article Barkoski J, Bennett D, Tancredi D, Barr DB, Elms W, Hertz-Picciotto I. Variability of urinary pesticide metabolite concentrations during pregnancy in the MARBLES Study. Environmental Research 2018;165:400-409. R835432 (2017)
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  • Journal Article Bauman MD, Iosif AM, Ashwood P, Braunschweig D, Lee A, Schumann CM, Van de Water J, Amaral DG. Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey. Translational Psychiatry 2013;3(7):e278 (12 pp.). R835432 (2013)
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  • Journal Article Berthelot CC, Kamita SG, Sacchi R, Yang J, Nording ML, Georgi K, Hegedus Karbowski C, German JB, Weiss RH, Hogg RJ, Hammock BD, Zivkovic AM. Changes in PTGS1 and ALOX12 gene expression in peripheral blood mononuclear cells are associated with changes in arachidonic acid, oxylipins, and oxylipin/fatty acid ratios in response to omega-3 fatty acid supplementation. PLoS One. 2015;10(12):e0144996 (13 pp.). R835432 (2015)
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  • Journal Article Braunschweig D, Krakowiak P, Duncanson P, Boyce R, Hansen RL, Ashwood P, Hertz-Picciotto I, Pessah IN, Van de Water J. Autism-specific maternal autoantibodies recognize critical proteins in developing brain. Translational Psychiatry 2013;3(7):e277. R835432 (2013)
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  • Journal Article 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, 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. R835432 (2016)
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  • Journal Article 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. R835432 (Final)
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  • Journal Article Camacho J, Jones K, Miller E, Ariza J, Noctor S, Van de Water J, Martinez-Cerdeno V. Embryonic intraventricular exposure to autism-specific maternal autoantibodies produces alterations in autistic-like stereotypical behaviors in offspring mice. Behavioural Brain Research 2014;266:46-51. R835432 (2013)
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  • Journal Article Cao Z, Hulsizer S, Cui Y, Pretto DL, Kim KH, Hagerman PJ, Tassone F, Pessah IN. Enhanced asynchronous Ca2+ oscillations associated with impaired glutamate transport in cortical astrocytes expressing Fmr1 gene premutation expansion. The Journal of Biological Chemistry 2013;288(19):13831-13841. R835432 (2013)
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  • Journal Article Cao Z, Cui Y, Nguyen HM, Jenkins DP, Wulff H, Pessah IN. Nanomolar bifenthrin alters synchronous Ca2+ oscillations and cortical neuron development independent of sodium channel activity. Molecular Pharmacology 2014;85(4):630-639. R835432 (2013)
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  • Journal Article Cao Z, Zou X, Cui Y, Hulsizer S, Lein PJ, Wulff H, Pessah IN. Rapid throughput analysis demonstrates that chemicals with distinct seizurogenic mechanisms differentially alter Ca2+ dynamics in networks formed by hippocampal neurons in culture. Molecular Pharmacology 2015;87(4):595-605. R835432 (2014)
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  • Journal Article Careaga M, Hansen RL, Hertz-Piccotto I, Van de Water J, Ashwood P. Increased anti-phospholipid antibodies in autism spectrum disorders. Mediators of Inflammation 2013;2013:935608, doi:10.1155/2013/935608. R835432 (2013)
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  • Journal Article Careaga M, Noyon T, Basuta K, Van de Water J, Tassone F, Hagerman RJ, Ashwood P. Group I metabotropic glutamate receptor mediated dynamic immune dysfunction in children with fragile X syndrome. Journal of Neuroinflammation 2014;11:110, doi:10.1186/1742-2094-11-110. R835432 (2014)
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  • Journal Article Careaga M, Rogers S, Hansen RL, Amaral DG, Van de Water J, Ashwood P. Immune endophenotypes in children with autism spectrum disorder. Biological Psychiatry 2015 Sep 11, doi:pii:S0006-3223(15)00738-6. 10.1016/j.biopsych.2015.08.036 [Epub ahead of print]. R835432 (2015)
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  • Journal Article Chen X, Walter KM, Miller GW, Lein PJ, Puschner B. Simultaneous quantification of T4, T3, rT3, 3,5-T2 and 3,3'-T2 in larval zebrafish (Danio rerio) as a model to study exposure to polychlorinated biphenyls. Biomedical Chromatography 2018;32(6):e4185. R835432 (2017)
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  • Journal Article Cherednichenko G, Zhang R, Bannister RA, Timofeyev V, Li N, Fritsch EB, Feng W, Barrientos GC, Schebb NH, Hammock BD, Beam KG, Chiamvimonvat N, Pessah IN. Triclosan impairs excitation-contraction coupling and Ca2+ dynamics in striated muscle. Proceedings of the National Academy of Sciences of the United States of America 2012;109(35):14158-14163. R835432 (2013)
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  • Journal Article Ciernia AV, LaSalle J. The landscape of DNA methylation amid a perfect storm of autism aetiologies. Nature Reviews Neuroscience 2016;17(7):411-423. R835432 (2015)
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  • Journal Article Crawley JN, Heyer W-D, LaSalle JM. Autism and cancer share risk genes, pathways, and drug targets. Trends in Genetics 2016;32(3):139-146. R835432 (2015)
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  • Journal Article Edmiston E, Jones KL, Vu T, Ashwood P, Van de Water J. Identification of the antigenic epitopes of maternal autoantibodies in autism spectrum disorders. Brain, Behavior, and Immunity 2018;69:399-407. R835432 (2017)
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  • Journal Article Fox-Edmiston E, Van de Water J. Maternal anti-fetal brain IgG autoantibodies and autism spectrum disorder: current knowledge and its implications for potential therapeutics. CNS Drugs 2015;29(9):715-724. R835432 (2015)
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  • Journal Article Girirajan S, Johnson RL, Tassone F, Balciuniene J, Katiyar N, Fox K, Baker C, Srikanth A, Yeoh KH, Khoo SJ, Nauth TB, Hansen R, Ritchie M, Hertz-Picciotto I, Eichler EE, Pessah IN, Selleck SB. Global increases in both common and rare copy number load associated with autism. Human Molecular Genetics 2013;22(14):2870-2880. R835432 (2013)
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  • Journal Article Goodrich AJ, Volk HE, Tancredi DJ, McConnell R, Lurmann FW, Hansen RL, Schmidt RJ. Joint effects of prenatal air pollutant exposure and maternal folic acid supplementation on risk of autism spectrum disorder. Austism Research 2018;11(1):69-80. R835432 (2017)
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  • Journal Article Harrill JA, Chen H, Streifel KM, Yang D, Mundy WR, Lein PJ. Ontogeny of biochemical, morphological and functional parameters of synaptogenesis in primary cultures of rat hippocampal and cortical neurons. Molecular Brain 2015;8:10 (15 pp.). R835432 (2014)
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  • Journal Article Jones KL, Croen LA, Yoshida CK, Heuer L, Hansen R, Zerbo O, DeLorenze GN, Kharrazi M, Yolken R, Ashwood P, Van de Water J. Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation. Molecular Psychiatry 2016 May 24, doi:10.1038/mp.2016.77 [Epub ahead of print]. R835432 (2015)
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  • Journal Article Keil KP, Lein PJ. DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? 2016;2(1):dvv012 (15 pp.). R835432 (2015)
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  • Journal Article Kerin T, Volk H, Li W, Lurmann F, Eckel S, McConnell R, Hertz-Picciotto I. Association between air pollution exposure, cognitive and adaptive function, and ASD severity among children with autism spectrum disorder. Journal of Autism and Developmental Disorders 2018;48(1):137-150. R835432 (2017)
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  • Journal Article Kim D, Volk H, Girirajan S, Pendergrass S, Hall MA, Verma SS, Schmidt RJ, Hansen RL, Ghosh D, Ludena-Rodriguez Y, Kim K, Ritchie MD, Hertz-Picciotto I, Selleck SB. The joint effect of air pollution exposure and copy number variation on risk for autism. Autism Research 2017;10(9):1470-1480. R835432 (2017)
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  • Journal Article Krakowiak P, Goines PE, Tancredi DJ, Ashwood P, Hansen RL, Hertz-Picciotto I, Van de Water J. Neonatal cytokine profiles associated with autism spectrum disorder. Biological Psychiatry 2017;81(5): 442-451. doi: 10.1016/j.biopsych.2015.08.007. R835432 (2015)
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  • Journal Article Krakowiak P, Walker CK, Tancredi DJ, Hertz-Picciotto I. Maternal recall versus medical records of metabolic conditions from the prenatal period: a validation study. Maternal and Child Health Journal 2015;19(9):1925-1935. R835432 (2014)
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  • Journal Article Krakowiak P, Walker CK, Tancredi D, Hertz-Picciotto I, Van de Water J. Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions. Autism Research 2017;10(1): 89-98. doi: 10.1002/aur.1657 R835432 (2015)
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  • Journal Article LaSalle JM. Epigenomic strategies at the interface of genetic and environmental risk factors for autism. Journal of Human Genetics 2013;58(7):396-401. R835432 (2013)
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  • Journal Article LaSalle JM. Autism genes keep turning up chromatin. OA Autism 2013;1(2):14. R835432 (2013)
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  • Journal Article Lesiak A, Zhu M, Chen H, Appleyard SM, Impey S, Lein PJ, Wayman GA. The environmental neurotoxicant PCB 95 promotes synaptogenesis via ryanodine receptor-dependent miR132 upregulation. The Journal of Neuroscience 2014;34(3):717-725. R835432 (2013)
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  • Journal Article Li X, Holland EB, Feng W, Zheng J, Dong Y, Pessah IN, Duffel MW, Robertson LW, Lehmler HJ. Authentication of synthetic environmental contaminants and their (bio)transformation products in toxicology: polychlorinated biphenyls as an example. Environmental Science and Pollution Research International 2018;25(17):16508-16521. R835432 (2017)
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  • Journal Article Lin YP, Pessah IN, Puschner B. Simultaneous determination of polybrominated diphenyl ethers and polychlorinated biphenyls by gas chromatography-tandem mass spectrometry in human serum and plasma. Talanta 2013;113:41-48. R835432 (2013)
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  • Journal Article Liu J, Koscielska KA, Cao Z, Hulsizer S, Grace N, Mitchell G, Nacey C, Githinji J, McGee J, Garcia-Arocena D, Hagerman RJ, Nolta J, Pessah IN, Hagerman PJ. Signaling defects in iPSC-derived fragile X premutation neurons. Human Molecular Genetics 2012;21(17):3795-3805. R835432 (2013)
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  • Journal Article Lyall K, Baker A, Hertz-Picciotto I, Walker CK. Infertility and its treatments in association with autism spectrum disorders: a review and results from the CHARGE study. International Journal of Environmental Research and Public Health 2013;10(8):3715-3734. R835432 (2013)
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  • Journal Article Lyall K, Schmidt RJ, Hertz-Picciotto I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. International Journal of Epidemiology 2014;43(2):443-464. R835432 (2013)
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  • Journal Article Lyall K, Ashwood P, Van de Water J, Hertz-Picciotto I. Maternal immune-mediated conditions, autism spectrum disorders, and developmental delay. Journal of Autism and Developmental Disorders 2014;44(7):1546-1555. R835432 (2013)
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  • Journal Article Lyall K, Van de Water J, Ashwood P, Hertz-Picciotto I. Asthma and allergies in children with autism spectrum disorders: results from the CHARGE Study. Autism Research 2015;8(5):567-574. R835432 (2014)
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  • Journal Article Martinez-Cerdeno V, Camacho J, Fox E, Miller E, Ariza J, Kienzle D, Plank K, Noctor SC, Van de Water J. Prenatal exposure to autism-specific maternal autoantibodies alters proliferation of cortical neural precursor cells, enlarges brain, and increases neuronal size in adult animals. Cerebral Cortex 2016;26(1):374-383. R835432 (2014)
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  • Journal Article Matelski L, Van de Water J. Risk factors in autism: thinking outside the brain. Journal of Autoimmunity 2016;67:1-7. R835432 (2015)
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  • Journal Article McKean SJ, Bartell SM, Hansen RL, Barfod GH, Green PG, Hertz-Picciotto I. Prenatal mercury exposure, autism, and developmental delay, using pharmacokinetic combination of newborn blood concentrations and questionnaire data: a case control study. Environmental Health 2015;14:62. R835432 (2014)
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  • Journal Article Miller GW, Chandrasekaran V, Yaghoobi B, Lein PJ. Opportunities and challenges for using the zebrafish to study neuronal connectivity as an endpoint of developmental neurotoxicity. NeuroToxicology; 2018;67:102-111. R835432 (2017)
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  • Journal Article Mitchell MM, Woods R, Chi L-H, Schmidt RJ, Pessah IN, Kostyniak PJ, LaSalle JM. Levels of select PCB and PBDE congeners in human postmortem brain reveal possible environmental involvement in 15q11-q13 duplication autism spectrum disorder. Environmental and Molecular Mutagenesis 2012;53(8):589-598. R835432 (2013)
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  • Journal Article Nguyen CT, Krakowiak P, Hansen R, Hertz-PicciottoI I, Angkustsiri K. Sociodemographic disparities in intervention service utilization in families of children with autism spectrum disorder. Journal of Autism and Developmental Disorders 2016. doi:10.1007/s10803-016-2913-3. R835432 (2015)
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  • Journal Article Philippat C, Bennett D, Calafat AM, Picciotto IH. Exposure to select phthalates and phenols through use of personal care products among Californian adults and their children. Environmental Research 2015;140:369-376. R835432 (2015)
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  • Journal Article Philippat C, Bennett DH, Krakowiak P, Rose M, Hwang HM, Hertz-Picciotto I. Phthalate concentrations in house dust in relation to autism spectrum disorder and developmental delay in the CHildhood Autism Risks from Genetics and the Environment (CHARGE) study. Environmental Health 2015;14:56 (10 pp.). R835432 (2014)
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  • Journal Article Philippat C, Barkoski J, Tancredi DJ, Elms B, Barr DB, Ozonoff S, Bennett DH, Hertz-Picciotto I. Prenatal exposure to organophosphate pesticides and risk of autism spectrum disorders and other non-typical development at 3 years in a high-risk cohort. International Journal of Hygiene and Environmental Health 2018;221(3):548-555. R835432 (2017)
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  • Journal Article Piras IS, Haapanen L, Napolioni V, Sacco R, Van de Water J, Persico AM. Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder. Brain, Behavior, and Immunity 2014;38:91-99. R835432 (2013)
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  • Journal Article Powell WT, LaSalle JM. Epigenetic mechanisms in diurnal cycles of metabolism and neurodevelopment. Human Molecular Genetics 2015;24(R1):R1-R9. R835432 (2015)
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  • Journal Article Pretto DI, Kumar M, Cao Z, Cunningham CL, Durbin-Johnson B, Qi L, Berman R, Noctor SC, Hagerman RJ, Pessah IN, Tassone F. Reduced excitatory amino acid transporter 1 and metabotropic glutamate receptor 5 expression in the cerebellum of fragile X mental retardation gene 1 premutation carriers with fragile X-associated tremor/ataxia syndrome. Neurobiology of Aging 2014;35(5):1189-1197. R835432 (2013)
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  • Journal Article Robin G, Lopez JR, Espinal GM, Hulsizer S, Hagerman PJ, Pessah IN. Calcium dysregulation and Cdk5-ATM pathway involved in a mouse model of fragile X-associated tremor/ataxia syndrome. Human Molecular Genetics 2017;26(14):2649-2666. R835432 (2017)
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  • Journal Article Rose DR, Yang H, Serena G, Sturgeon C, Ma B, Careaga M, Hughes HK, Angkustsiri K, Rose M, Hertz-Picciotto I, Van de Water J, Hansen RL, Ravel J, Fasano A, Ashwood P. Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms. Brain, Behavior, and Immunity 2018;70:354-368. R835432 (2017)
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  • Journal Article Rossi CC, Fuentes J, Van de Water J, Amaral DG. Brief report: antibodies reacting to brain tissue in Basque Spanish children with Autism Spectrum Disorder and their mothers. Journal of Autism and Developmental Disorders 2014;44(2):459-465. R835432 (2013)
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  • Journal Article Saldarriaga W, Lein P, Gonzalez Teshima LY, Isaza C, Rosa L, Polyak A, Hagerman R, Girirajan S, Silva M, Tassone F. Phenobarbital use and neurological problems in FMR1 premutation carriers. NeuroToxicology 2016;53:141-147. R835432 (2015)
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  • Journal Article Schmidt RJ, Tancredi DJ, Krakowiak P, Hansen RL, Ozonoff S. Maternal intake of supplemental iron and risk of autism spectrum disorder. American Journal of Epidemiology 2014;180(9):890-900. R835432 (2014)
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  • Journal Article Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Sconberg JL, Schmidt LC, Volk HE, Tassone F. Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study. Early Human Development 2015;91(8):483-489. R835432 (2014)
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  • Journal Article Schmidt RJ, Kogan V, Shelton JF, Delwiche L, Hansen RL, Ozonoff S, Ma CC, McCanlies EC, Bennett DH, Hertz-Picciotto I, Tancredi DJ, Volk HE. Combined prenatal pesticide exposure and folic acid intake in relation to autism spectrum disorder. Environmental Health Perspectives 2017;125(9):097007 (12 pp.). R835432 (2017)
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  • Journal Article Sethi S, Keil KP, Chen H, Hayakawa K, Li X, Lin Y, Lehmler HJ, Puschner B, Lein PJ. Detection of 3,3'-dichlorobiphenyl in human maternal plasma and its effects on axonal and dendritic growth in primary rat neurons. Toxicological Sciences 2017;158(2):401-411. R835432 (2017)
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  • Journal Article Sethi S, Keil K, Lein P. Species and sex differences in the morphogenic response of primary rodent neurons to 3, 3′-dichlorobiphenyl (PCB 11). Toxics 2018;6(1): 4. doi: 10.3390/toxics6010004 R835432 (2017)
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  • Journal Article Shelton JF, Hertz-Picciotto I, Pessah IN. Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environmental Health Perspectives 2012;120(7):944-951. R835432 (2013)
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  • Journal Article Sirish P, Li N, Timofeyev V, Zhang XD, Wang L, Yang J, Lee KS, Bettaieb A, Ma SM, Lee JH, Su D, Lau VC, Myers RE, Lieu DK, Lopez JE, Young JN, Yamoah EN, Haj F, Ripplinger CM, Hammock BD, Chiamvimonvat N. Molecular mechanisms and new treatment paradigm for atrial fibrillation. Circulation: Arrhythmia and Electrophysiology 2016;9(5): e003721. R835432 (2015)
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  • Journal Article Stamou M, Uwimana E, Flannery BM, Kania-Korwel I, Lehmler HJ, Lein PJ. Subacute nicotine co-exposure has no effect on 2,2',3,5',6-pentachlorobiphenyl disposition but alters hepatic cytochrome P450 expression in the male rat. Toxicology 2015;338:59-68. R835432 (2015)
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  • Journal Article Stamou M, Grodzki AC, van Oostrum M, Wollscheid B, Lein PJ. Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex. Journal of Neuroinflammation 2018;15(1):7 (23 pp.). R835432 (2017)
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  • Journal Article Vogel CFA, Wu D, Goth SR, Baek J, Lollies A, Domhardt R, Grindel A, Pessah IN. Aryl hydrocarbon receptor signaling regulates NF-κB RelB activation during dendritic-cell differentiation. Immunology and Cell Biology 2013;91(9):568-575. R835432 (2013)
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  • Journal Article Walker CK, Krakowiak P, Baker A, Hansen RL, Ozonoff S, Hertz-Picciotto I. Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. Journal of the American Medical Association Pediatrics 2015;169(2):154-162. R835432 (2014)
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  • Journal Article Wayman GA, Bose DD, Yang D, Lesiak A, Bruun D, Impey S, Ledoux V, Pessah IN, Lein PJ. PCB-95 modulates the calcium-dependent signaling pathway responsible for activity-dependent dendritic growth. Environmental Health Perspectives 2012;120(7):1003-1009. R835432 (2013)
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  • Journal Article Zheng J, McKinnie SMK, El Gamal A, Feng W, Dong Y, Agarwal V, Fenical W, Kumar A, Cao Z, Moore BS, Pessah IN. Organohalogens naturally biosynthesized in marine environments and produced as disinfection byproducts alter sarco/endoplasmic reticulum Ca2+ dynamics. Environmental Science & Technology 2018;52(9):5469-5478. R835432 (2017)
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  • Journal Article Tassone F, Choudhary NS, Tassone F, Durbin-Johnson B, Hansen R, Hertz-Picciotto I, Pessah I. Identification of expanded alleles of the FMR1 gene in the CHildhood Autism Risks from Genes and Environment (CHARGE) study. Journal of Autism and Developmental Disorders 2013;43(3):530-539. R835432 (Final)
    R833292 (2012)
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  • Journal Article Wu X, Kania-Korwel I, Chen H, Stamou M, Dammanahalli KJ, Duffel M, Lein PJ, Lehmler HJ. Metabolism of 2, 2′, 3, 3′, 6, 6′-hexachlorobiphenyl (PCB 136) atropisomers in tissue slices from phenobarbital or dexamethasone-induced rats is sex-dependent. Xenobiotica 2013;43(11):933-947 R835432 (Final)
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  • Journal Article Stamou M, Streifel KM, Goines PE, Lein PJ. Neuronal connectivity as a convergent target of gene-environment interactions that confer risk for Autism Spectrum Disorders. Neurotoxicology and teratology 2013;36:3-16. doi:10.1016/j.ntt.2012.12.001. Review. R835432 (Final)
  • Abstract: Evidence implicates environmental factors in the pathogenesis of Autism Spectrum Disorders (ASD). However, the identity of specific environmental chemicals that influence ASD risk, severity or treatment outcome remains elusive. The impact of any given environmental exposure likely varies across a population according to individual genetic substrates, and this increases the difficulty of identifying clear associations between exposure and ASD diagnoses. Heritable genetic vulnerabilities may amplify adverse effects triggered by environmental exposures if genetic and environmental factors converge to dysregulate the same signaling systems at critical times of development. Thus, one strategy for identifying environmental risk factors for ASD is to screen for environmental factors that modulate the same signaling pathways as ASD susceptibility genes. Recent advances in defining the molecular and cellular pathology of ASD point to altered patterns of neuronal connectivity in the developing brain as the neurobiological basis of these disorders. Studies of syndromic ASD and rare highly penetrant mutations or CNVs in ASD suggest that ASD risk genes converge on several major signaling pathways linked to altered neuronal connectivity in the developing brain. This review briefly summarizes the evidence implicating dysfunctional signaling via Ca(2+)-dependent mechanisms, extracellular signal-regulated kinases (ERK)/phosphatidylinositol-3-kinases (PI3K) and neuroligin-neurexin-SHANK as convergent molecular mechanisms in ASD, and then discusses examples of environmental chemicals for which there is emerging evidence of their potential to interfere with normal neuronal connectivity via perturbation of these signaling pathways.
  • Journal Article Walker CK, Anderson KW, Milano KM, Ye S, Tancredi DJ, Pessah IN, Hertz-Picciotto I, Kliman HJ. Trophoblast inclusions are significantly increased in the placentas of children in families at risk for autism. Biological Psychiatry 2013;74(3):204-211. doi:10.1016/j.biopsych.2013.03.006. R835432 (Final)
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  • Journal Article Yang D, Kania-Korwel I, Ghogha A, Chen H, Stamou M, Bose DD, Pessah IN, Lehmler HJ, Lein PJ. PCB 136 atropselectively alters morphometric and functional parameters of neuronal connectivity in cultured rat hippocampal neurons via ryanodine receptor-dependent mechanisms. Toxicological Sciences 2014;138(2):379-392 R835432 (Final)
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  • Journal Article Pretto DI, Kumar M, Cao Z, Cunningham CL, Durbin-Johnson B, Qi L, Berman R, Noctor SC, Hagerman RJ, Pessah IN, Tassone F. Reduced EAAT1 and mGluR5 expression in the cerebellum of Fmr1 premutation carriers with FXTAS. Neurobiology of Aging 2014;35(5):1189. doi:10.1016/j.neurobiolaging.2013.11.009. R835432 (Final)
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  • Journal Article Schroeder DI, Jayashankar K, Douglas KC, Thirkill TL, York D, Dickinson PJ, Williams LE, Samollow PB, Ross PJ, Bannasch DL, Douglas GC, LaSalle JM. Early developmental and evolutionary origins of gene body DNA methylation patterns in mammalian placentas. PLOS Genetics 2015;11(8):e1005442. doi:10.1371/journal.pgen.1005442. R835432 (Final)
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  • Journal Article Fritsch EB, Stegeman JJ, Goldstone JV, Nacci DE, Champlin D, Jayaraman S, Connon RE, Pessah IN. Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA. Aquatic Toxicology 2015;159:156-166. doi:10.1016/j.aquatox.2014.12.017. R835432 (Final)
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  • Journal Article Bal-Price A, Crofton KM, Sachana M, Shafer TJ, Behl M, Forsby A, Hargreaves A, Landesmann B, Lein PJ, Louisse J, Monnet-Tschudi F. Putative adverse outcome pathways relevant to neurotoxicity. Critical Reviews in Toxicology 2015;45(1):83-91 R835432 (Final)
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  • Journal Article Vogel Ciernia A, LaSalle JM. The landscape of DNA methylation amidst a perfect storm of autism etiologies. Nature Reviews Neuroscience 2016;17:411-23. doi:10.1038/nrn.2016.41. R835432 (Final)
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  • Journal Article Holland EB, Feng W, Zheng J, Dong Y, Li X, Lehmler HJ, Pessah IN. An extended structure–activity relationship of nondioxin-like PCBs evaluates and supports modeling predictions and identifies picomolar potency of PCB 202 towards ryanodine receptors. Toxicological Sciences 2016;155(1):170-181. doi:10.1093/toxsci/kfw189. R835432 (Final)
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  • Journal Article Dunaway KW, Islam MS, Coulson RL, Lopez SJ, Vogel Ciernia A, Chu RG, Yasui DH, Pessah IN, Lott P, Mordaunt C, Meguro-Horike M, Horike S, Korf I, LaSalle JM. Cumulative impact of polychlorinated biphenyl and large chromosomal duplications on DNA methylation, chromatin, and expression of autism genes. Cell Reports 2016;17(11):3035-3048. doi:10.1016/j.celrep.2016.11.058. R835432 (Final)
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  • Journal Article Schroeder DI, Schmidt RJ, Crary-Dooley FK, Walker CK, Ozonoff S, Tancredi DJ, Hertz-Picciotto I, LaSalle JM. Placental methylome analysis from a prospective autism study. Molecular Autism 2016;7:51. R835432 (Final)
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  • Journal Article Schmidt RJ, Schroeder DI, Crary-Dooley FK, Barkoski JM, Tancredi DJ, Walker CK, Ozonoff S, Hertz-Picciotto I, LaSalle JM. Self-reported pregnancy exposures and placental DNA methylation in the MARBLES prospective autism sibling study. Environmental Epigenetics 2016;2(4):dvw024. R835432 (Final)
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  • Journal Article Crary-Dooley FK, Tam ME, Dunaway KW, Hertz-Picciotto I, Schmidt RJ, LaSalle JM. A comparison of existing global DNA methylation assays to low-coverage whole genome bisulfite sequencing for epidemiology studies. Epigenetics 2017;12(3):206-214. doi:10.1080/15592294.2016.127668. R835432 (Final)
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  • Journal Article Mengeling BJ, Wei Y, Dobrawa LN, Streekstra M, Louisse J, Singh V, Singh L, Lein PJ, Wulff H, Murk AJ, Furlow JD. A multi-tiered, in vivo, quantitative assay suite for environmental disruptors of thyroid hormone signaling. Aquatic Toxicology 2017;190:1-0. doi:0.1016/j.aquatox.2017.06.019. R835432 (Final)
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  • Journal Article Careaga M, Rogers S, Hansen RL, Amaral DG, Van de Water J, Ashwood P. Immune endophenotypes in children with autism spectrum disorder. Biological Psychiatry 2017;81(5): 434-441. R835432 (2016)
    R835432 (Final)
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  • Journal Article Onore C, Yang H, Van de Water J, Ashwood P. Dynamic Akt/mTOR signaling in children with autism spectrum disorder. Frontiers in Pediatrics 2017;5:43. R835432 (2016)
    R835432 (Final)
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  • Journal Article Kania-Korwel I, Lukasiewicz T, Barnhart CD, Stamou M, Chung H, Kelly KM, Bandiera S, Lein PJ, Lehmler HJ. Editor’s highlight:Congener-specific disposition of chiral polychlorinated biphenyls in lactating mice and their offspring:Implications for PCB developmental neurotoxicity. Toxicological Sciences 2017;158(1):101-115. doi:10.1093/toxsci/kfx071. R835432 (Final)
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  • Journal Article Feng W, Zheng J, Robin G, Dong Y, Ichikawa M, Inoue Y, Mori T, Nakano T, Pessah IN. Enantioselectivity of 2, 2′, 3, 5′, 6-pentachlorobiphenyl (PCB 95) atropisomers toward ryanodine receptors (RyRs) and their influences on hippocampal neuronal networks. Environmental Science & Technology 2017;51(24):14406-14416. doi:10.1021/acs.est.7b04446. R835432 (Final)
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  • Journal Article Rose DR, Careaga M, Van de Water J, McAllister K, Bauman MD, Ashwood P. Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation. Brain, Behavior, and Immunity 2017;63:60-70. doi:10.1016/j.bbi.2016.11.020. R835432 (Final)
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  • Journal Article Lim ET, Uddin M, De Rubeis S, Chan Y, Kamumbu AS, Zhang X, D'Gama AM, Kim SN, Hill RS, Goldberg AP, Poultney C. Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Nature Neuroscience 2017;20(9):1217-1224. doi:10.1038/nn.4598. R835432 (Final)
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  • Journal Article Meltzer A, Van de Water J. The role of the immune system in autism spectrum disorder. Neuropsychopharmacology 2017;42(1):284-298. doi:10.1038/npp.2016.158. R835432 (Final)
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  • Journal Article Frank DF, Miller GW, Connon RE, Geist J, Lein PJ. Transcriptomic profiling of mTOR and ryanodine receptor signaling molecules in developing zebrafish in the absence and presence of PCB 95. PeerJ 2017;5:e4106. doi:10.7717/peerj.4106. R835432 (Final)
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  • Journal Article Frank DF, Miller GW, Harvey DJ, Brander SM, Geist J, Connon RE, Lein PJ. Bifenthrin causes transcriptomic alterations in mTOR and ryanodine receptor-dependent signaling and delayed hyperactivity in developing zebrafish (Danio rerio). Aquatic Toxicology 2018;200:50-61. R835432 (Final)
    R835799 (2018)
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  • Journal Article Sethi S, Keil KP, Lein PJ. 3, 3ʹ-Dichlorobiphenyl (PCB 11) promotes dendritic arborization in primary rat cortical neurons via a CREB-dependent mechanism. Archives of Toxicology 2018;92(11):3337-3345. doi:10.1007/s00204-018-2307-8. R835432 (Final)
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  • Journal Article Hertz-Picciotto I, Schmidt RJ, Walker CK, Bennett DH, Oliver M, Shedd-Wise KM, LaSalle JM, Giulivi C, Puschner B, Thomas J, Roa DL. A prospective study of environmental exposures and early biomarkers in autism spectrum disorder:design, protocols, and preliminary data from the MARBLES study. Environmental Health Perspectives 2018;126(11):117004. doi:10.1289/EHP535. R835432 (Final)
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  • Journal Article Hertz-Picciotto I, Schmidt RJ, Walker CK, Bennett DH, Oliver M, Wise K, Giulivi C, Puschner B, Thomas J, Lasalle JM, Pessah I, Van de Water J, Ozonoff S. A prospective study of environmental exposures and early biomarkers.Environmental Health Perspectives 2018;126(11):117004. R835432 (Final)
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  • Journal Article Truong KM, Pessah IN. Comparison of chlorantraniliprole and flubendiamide activity toward wild-type and malignant hyperthermia-susceptible ryanodine receptors and heat stress intolerance. Toxicological Sciences 2018;167(2):509-523. doi:10.1093/toxsci/kfy256. R835432 (Final)
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  • Journal Article Dou J, Schmidt RJ, Benke KS, Newschaffer C, Hertz-Picciotto I, Croen LA, Iosif A-M, LaSalle JM, Fallin MD, Bakilski K. Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation. Epigenetics 2018;13(1):108-116. doi:10.1080/15592294.2017.1417710. R835432 (Final)
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  • Journal Article Hollowood K, Melnyk S, Pavliv O, Evans T, Sides A, Schmidt RJ, Hertz-Picciotto I, Elms W, Guerrero E, Kruger U, Hahn J, James SJ. Maternal metabolic profile predicts high or low risk of an autism pregnancy outcome. Research in Autism Spectrum Disorders 2018;56:72-82. doi:10.1016/j.rasd.2018.09.003. R835432 (Final)
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  • Journal Article Zheng J, McKinnie SM, El Gamal A, Feng W, Dong Y, Agarwal V, Fenical W, Kumar A, Cao Z, Moore BS, Pessah IN. Organohalogens naturally biosynthesized in marine environments and produced as disinfection byproducts alter sarco/endoplasmic reticulum Ca2+ dynamics. Environmental Science & Technology 2018;52(9):5469-5478 R835432 (Final)
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  • Journal Article Hertz-Picciotto I, Krakowiak P, Schmidt R. Understanding environmental contributions to autism:casual concepts and the state of the science. Autism Research 2018;11(4):554-586. R835432 (Final)
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  • Journal Article Careaga M, Taylor SL, Chang C, Chiang A, Ku KM, Berman RF, Van de Water J, Bauman MD. Variability in PolyIC induced immune response:implications for preclinical maternal immune activation models. Journal of Neuroimmunology 2018;323:87-93. doi:10.1016/j.jneuroim.2018.06.014. R835432 (Final)
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  • Journal Article Zheng J, Yu Y, Feng W, Li J, Liu J, Zhang C, Dong Y, Pessah IN, Cao Z. Influence of nanomolar deltamethrin on the hallmarks of primary cultured cortical neuronal network and the role of ryanodine receptors. Environmental Health Perspectives 2019;127(6):67003 R835432 (Final)
    R829388 (Final)
    R833292 (Final)
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  • Journal Article McCanlies EC, Ma CC, Gu JK, Fekedulegn D, Sanderson WT, Hertz-Piccioto I. The CHARGE Study:An assessment of parental occupational exposures and autism spectrum disorder. Occupational and Environmental Medicine 2019;76:644–651 R835432 (Final)
    R829388 (Final)
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  • Journal Article Pessah IN, Truong K. Additional Safety Assessments Needed for Diamide Insecticides.STOXICOLOGICAL SCIENCES 2019:170(2):509-524 R835432 (Final)
    R833292 (Final)
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  • Journal Article Walter KM, Miller GW, Chen X, Harvey DJ, Puschner B, Lein PJ. Changes in thyroid hormone activity disrupt photomotor behavior of larval zebrafish. Neurotoxicology 2019;74:47-57 R835432 (Final)
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  • Journal Article Stamou M, Lein PJ. Commentary: Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex. Journal of Neurology & Neuromedicine 2019;4(1):26. doi:10.29245/2572.942X/2019/1.1243. R835432 (Final)
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  • Journal Article Sethi S, Morgan RK, Feng W, Lin Y, Li X, Luna C, Koch M, Bansal R, Duffel MW, Puschner B, Zoeller RT. Comparative analyses of the 12 most abundant PCB congeners detected in human maternal serum for activity at the thyroid hormone receptor and ryanodine receptor. Environmental science & technology 2019;53(7):3948-3958. doi:10.1021/acs.est.9b00535. R835432 (Final)
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  • Journal Article Frank DF, Brander SM, Hasenbein S, Harvey DJ, Lein PJ, Geist J, Connon RE. Developmental exposure to environmentally relevant concentrations of bifenthrin alters transcription of mTOR and ryanodine receptor-dependent signaling molecules and impairs predator avoidance behavior across early life stages in inland silversides (Menidia beryllina). Aquatic toxicology 2019;206:1-13. doi:10.1016/j.aquatox.2018.10.014. R835432 (Final)
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  • Journal Article Rude KM, Pusceddu MM, Keogh CE, Sladek JA, Rabasa G, Miller EN, Sethi S, Keil KP, Pessah IN, Lein PJ, Gareau MG. Developmental exposure to polychlorinated biphenyls (PCBs) in the maternal diet causes host-microbe defects in weanling offspring mice. Environmental Pollution 2019;253:708-721. doi:10.1016/j.envpol.2019.07.066. R835432 (Final)
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  • Journal Article Walter KM, Miller GW, Chen X, Yaghoobi B, Puschner B, Lein PJ. Effects of thyroid hormone disruption on the ontogenetic expression of thyroid hormone signaling genes in developing zebrafish (Danio rerio). General and Comparative Endocrinology 2019;272:20-32 R835432 (Final)
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  • Journal Article Keil KP, Sethi S, Wilson MD, Silverman JL, Pessah IN, Lein PJ. Genetic mutations in Ca2+ signaling alter dendrite morphology and social approach in juvenile mice. Genes, Brain and Behavior 2019;18(1):e12526. doi:10.1111/gbb.12526. R835432 (Final)
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  • Journal Article Saldarriaga W, Salcedo-Arellano MJ, Rodriguez-Guerrero T, Ríos M, Fandino-Losada A, Ramirez-Cheyne J, Lein PJ, Tassone F, Hagerman RJ. Increased severity of fragile X spectrum disorders in the agricultural community of Ricaurte, Colombia. International Journal of Developmental Neuroscience 2019;72:1-5. doi:10.1016/j.ijdevneu.2018.10.002. R835432 (Final)
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  • Journal Article Truong KM, Cherednichenko G, Pessah IN. Interactions of dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) with skeletal muscle ryanodine receptor type 1. Toxicological Sciences 2019;170(2):509-524. doi:10.1093/toxsci/kfz120. R835432 (Final)
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  • Journal Article Kupers LK, Monnereau C, Sharp GC, Yousefi P, Salas LA, Ghantous A, Page CM, Reese SE, Wilcox AJ, Czamara D, Starling AP, Novoloaca A, Lent S, Roy R, Hoyo C, Breton CV, Allard C, Just AC, Bakulski KM, Holloway JW, Everson TM, Xu CJ, Huang RC, van der Plaat DA, Wielscher M, Merid SK, Ullemar V, Rezwan FI, Lahti J, van Dongen J, Langie SAS, Richardson TG, Magnus MC, Nohr EA, Xu Z, Duijts L, Zhao S, Zhang W, Plusquin M, DeMeo DL, Solomon O, Heimovaara JH, Jima DD, Gao L, Bustamante M, Perron P, Wright RO, Hertz-Picciotto I, Zhang H, Karagas MR, Gehring U, Marsit CJ, Beilin LJ, Vonk JM, Jarvelin MR, Bergstrom A, Ortqvist AK, Ewart S, Villa PM, Moore SE, Willemsen G, Standaert ARL, Haberg SE, Sorensen TIA, Taylor JA, Raikkonen K, Yang IV, Kechris K, Nawrot TS, Silver MJ, Gong YY, Richiardi L, Kogevinas M, Litonjua AA, Eskenazi B, Huen K, Mbarek H, Maguire RL, Dwyer T, Vrijheid M, Bouchard L, Baccarelli AA, Croen LA, Karmaus W, Anderson D, de Vries M, Sebert S, Kere J, Karlsson R, Arshad SH, Hamalainen E, Routledge MN, Boomsma DI, Feinberg AP, Newschaffer CJ, Govarts E, Moisse M, Fallin MD, Melen E, Prentice AM, Kajantie E, Almqvist C, Oken E, Dabelea D, Boezen HM, Melton PE, Wright RJ, Koppelman GH, Trevisi L, Hivert MF, Sunyer J, Munthe-Kaas MC, Murphy SK, Corpeleijn E, Wiemels J, Holland N, Herceg Z, Binder EB, Davey Smith G, Jaddoe VWV, Lie RT, Nystad W, London SJ, Lawlor DA, Relton CL, Snieder H, Felix JF. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight. Nature Communications 2019;10(1):1893. R835432 (Final)
    R835442 (Final)
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  • Journal Article Pessah IN, Lein PJ, Seegal RF, Sagiv SK. Neurotoxicity of polychlorinated biphenyls and related organohalogens. Acta Neuropathologica 2019;138(3):363-387. doi:10.1007/s00401-019-01978-1. R835432 (Final)
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    Journal Article Walter KM, Dach K, Hayakawa K, Giersiefer S, Heuer H, Lein PJ, Fritsche E. Ontogenetic expression of thyroid hormone signaling genes:an in vitro and in vivo species comparison. PloS One 2019;14(9):e0221230 R835432 (Final)
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  • Journal Article Zhu Y, Mordaunt CE, Yasui DH, Marathe R, Coulson R, Dunaway K, Walker C, Ozonoff S, Hertz-Picciotto I, Schmidt RJ, LaSalle JM. Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study. Human Molecular Genetics 2019;28(16):2659-2674 R835432 (Final)
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  • Journal Article Zheng J, Chen J, Zou X, Zhao F, Guo M, Wang H, Zhang T, Zhang C, Feng W, Pessah IN, Cao Z. Saikosaponin d causes apoptotic death of cultured neocortical neurons by increasing membrane permeability and elevating intracellular Ca2+ concentration. Neurotoxicology 2019;70:112-21 R835432 (Final)
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  • Journal Article Dach K, Yaghoobi B, Schmuck MR, Carty DR, Morales KM, Lein PJ. Teratological and behavioral screening of the national toxicology program 91-compound library in zebrafish (Danio rerio). Toxicological Sciences 2019;167(1):77-91. doi:10.1093/toxsci/kfy266. R835432 (Final)
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  • Journal Article Krakowiak, Paula; Walker, Cheryl K; Tancredi, Daniel; Hertz-Picciotto, Irva; Van de Water, Judy Autism research:official journal of the International Society for Autism Research.2017 Jan;Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions. R835432 (2016)
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    Journal Article Mordaunt CE, Park BY, Bakulski KM, Feinberg JI, Croen LA, Ladd-Acosta C, Newschaffer CJ, Volk HE, Ozonoff S, Hertz-Picciotto I, LaSalle JM. A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood. BioRxiv 2019. doi:10.1101/486498. R835432 (Final)
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  • Journal Article Aschner M, Ceccatelli S, Daneshian M, Fritsche E, Hasiwa N, Hartung T, Hogberg HT, Leist M, Li A, Mundy WR, Padilla S. Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use. Altex 2017;34(1):49. R835432 (2016)
    R835432 (Final)
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  • Journal Article Wong S, Giulivi C. Autism, mitochondria and polybrominated diphenyl ether exposure. CNS & Neurological Disorders-Drug Targets. 2016 May 1;15(5): 614-623. R835432 (2016)
    R835432 (Final)
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  • Journal Article Krakowiak, Paula; Goines, Paula E; Tancredi, Daniel J; Ashwood, Paul; Hansen, Robin L; Hertz-Picciotto, Irva; Van de Water, Judy. Biological psychiatry.2017 Mar 01;Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder. R835432 (2016)
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    Journal Article Edmiston, Elizabeth; Ashwood, Paul; Van de Water, Judy . Biological psychiatry. 2017 Mar 01; Autoimmunity, Autoantibodies, and Autism Spectrum Disorder. R835432 (2016)
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    Journal Article Tylee DS, Hess JL, Quinn TP, Barve R, Huang H, Zhang‐James Y, Chang J, Stamova BS, Sharp FR, Hertz‐Picciotto I, Faraone SV. Blood transcriptomic comparison of individuals with and without autism spectrum disorder: a combined‐samples mega‐analysis. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 2017;174(3): 181-201. R835432 (2016)
    R835432 (Final)
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  • Journal Article Dunaway, Keith W; Islam, M Saharul; Coulson, Rochelle L; Lopez, S Jesse; Vogel Ciernia, Annie; Chu, Roy G; Yasui, Dag H; Pessah, Isaac N; Lott, Paul; Mordaunt, Charles; Meguro-Horike, Makiko; Horike, Shin-Ichi; Korf, Ian; LaSalle, Janine M. Cell reports. 2016 Dec 13; Cumulative Impact of Polychlorinated Biphenyl and Large Chromosomal Duplications on DNA Methylation, Chromatin, and Expression of Autism Candidate Genes. R835432 (2016)
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    Journal Article Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy. Cerebral cortex. 2016 Jan; Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals. R835432 (2016)
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    Journal Article Sirish, Padmini; Li, Ning; Timofeyev, Valeriy; Zhang, Xiao-Dong; Wang, Lianguo; Yang, Jun; Lee, Kin Sing Stephen; Bettaieb, Ahmed; Ma, Sin Mei; Lee, Jeong Han; Su, Demetria; Lau, Victor C; Myers, Richard E; Lieu, Deborah K; López, Javier E; Young, J Nilas; Yamoah, Ebenezer N; Haj, Fawaz; Ripplinger, Crystal M; Hammock, Bruce D; Chiamvimonvat, Nipavan. Circulation. Arrhythmia and electrophysiology. 2016 May; Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation. R835432 (2016)
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    Journal Article Zhang R, Pessah IN. Divergent mechanisms leading to signaling dysfunction in embryonic muscle by bisphenol A and tetrabromobisphenol A. Molecular Pharmacology 2017;91(4): 428-436. R835432 (2016)
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  • Journal Article Vogel Ciernia A, Pride MC, Durbin-Johnson B, Noronha A, Chang A, Yasui DH, Crawley JN, LaSalle JM. Early motor phenotype detection in a female mouse model of Rett syndrome is improved by cross-fostering. Human Molecular Genetics 2017;26(10): 1839-1854. R835432 (2016)
    R835432 (Final)
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  • Journal Article Keil KP, Lein PJ. DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders?. Environmental Epigenetics 2016;2(1). R835432 (2016)
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  • Journal Article Schmidt, Rebecca J; Schroeder, Diane I; Crary-Dooley, Florence K; Barkoski, Jacqueline M; Tancredi, Daniel J; Walker, Cheryl K; Ozonoff, Sally; Hertz-Picciotto, Irva; LaSalle, Janine M. Environmental epigenetics. 2016 Dec; Self-reported pregnancy exposures and placental DNA methylation in the MARBLES prospective autism sibling study. R835432 (2016)
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    Journal Article Crary-Dooley, Florence K; Tam, Mitchell E; Dunaway, Keith W; Hertz-Picciotto, Irva; Schmidt, Rebecca J; LaSalle, Janine M. Epigenetics. 2017 Mar 04; A comparison of existing global DNA methylation assays to low-coverage whole-genome bisulfite sequencing for epidemiological studies. R835432 (2016)
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    Journal Article Vogel Ciernia A, Laufer BI, Dunaway KD, Mordaunt CE, Coulson RL, Yasui DH, LaSalle JM. Epigenomic convergence of neural-immune risk factors in neurodevelopmental disorder cortex. Cerebral Cortex 2019. doi:10.1093/cercor/bhz115. R835432 (Final)
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  • Journal Article Nguyen, Cathina T; Krakowiak, Paula; Hansen, Robin; Hertz-Picciotto, Irva; Angkustsiri, Kathleen. Journal of autism and developmental disorders. 2016 Dec; Sociodemographic Disparities in Intervention Service Utilization in Families of Children with Autism Spectrum Disorder. R835432 (2016)
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    Journal Article Matelski, Lauren; Van de Water, Judy. Journal of autoimmunity. 2016 Feb; Risk factors in autism:Thinking outside the brain. R835432 (2016)
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    Journal Article Schroeder, Diane I; Schmidt, Rebecca J; Crary-Dooley, Florence K; Walker, Cheryl K; Ozonoff, Sally; Tancredi, Daniel J; Hertz-Picciotto, Irva; LaSalle, Janine M. Molecular autism. 2016; Placental methylome analysis from a prospective autism study. R835432 (2016)
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    Journal Article Jones, K L; Croen, L A; Yoshida, C K; Heuer, L; Hansen, R; Zerbo, O; DeLorenze, G N; Kharrazi, M; Yolken, R; Ashwood, P; Van de Water, J. Molecular psychiatry. Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation. R835432 (2016)
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    Journal Article Vogel Ciernia, Annie; LaSalle, Janine. Nature reviews. Neuroscience. 2016 07; The landscape of DNA methylation amid a perfect storm of autism aetiologies. R835432 (2016)
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    Journal Article Bal-Price A, Lein PJ, Keil KP, Sethi S, Shafer T, Barenys M, Fritsche E, Sachana M, Meek MB. Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity. Neurotoxicology 2017;59: 240-55. R835432 (2016)
    R835432 (Final)
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  • Journal Article Chen X, Lin Y, Dang K, Puschner B. Quantification of polychlorinated biphenyls and polybrominated diphenyl ethers in commercial cows’ milk from California by gas chromatography-triple quadruple mass spectrometry. PloS One 2017;12(1): e0170129. R835432 (2016)
    R835432 (Final)
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  • Journal Article Saldarriaga W, Lein P, Teshima LY, Isaza C, Rosa L, Polyak A, Hagerman R, Girirajan S, Silva M, Tassone F. Phenobarbital use and neurological problems in FMR1 premutation carriers. Neurotoxicology 2016;53: 141-147. R835432 (2016)
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  • Journal Article Sethi S, Chen X, Kass PH, Puschner B. Polychlorinated biphenyl and polybrominated diphenyl ether profiles in serum from cattle, sheep, and goats across California. Chemosphere 2017;181: 63-73. R835432 (2016)
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  • Journal Article Ronjat, Michel; Feng, Wei; Dardevet, Lucie; Dong, Yao; Al Khoury, Sawsan; Chatelain, Franck C; Vialla, Virginie; Chahboun, Samir; Lesage, Florian; Darbon, Hervé; Pessah, Isaac N; De Waard, Michel. Proceedings of the National Academy of Sciences of the United States of America. 2016 Apr 26; In cellulo phosphorylation induces pharmacological reprogramming of maurocalcin, a cell-penetrating venom peptide. R835432 (2016)
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    Journal Article Wong S, Napoli E, Krakowiak P, Tassone F, Hertz-Picciotto I, Giulivi C. Role of p53, mitochondrial DNA deletions, and paternal age in autism: a case-control study. Pediatrics 2016;137(4): e20151888. R835432 (2016)
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  • Full-text: Pediatrics-Full text
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  • Journal Article Dach K, Bendt F, Huebenthal U, Giersiefer S, Lein PJ, Heuer H, Fritsche E. BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action. Scientific Reports 2017;7: 44861. R835432 (2016)
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  • Journal Article Dunaway, Keith; Goorha, Sarita; Matelski, Lauren; Urraca, Nora; Lein, Pamela J; Korf, Ian; Reiter, Lawrence T; LaSalle, Janine M. Stem cells (Dayton, Ohio).2017 Apr;Dental Pulp Stem Cells Model Early Life and Imprinted DNA Methylation Patterns. R835432 (2016)
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    Journal Article Holland, Erika B; Feng, Wei; Zheng, Jing; Dong, Yao; Li, Xueshu; Lehmler, Hans-Joachim; Pessah, Isaac N. Toxicological sciences:an official journal of the Society of Toxicology. An Extended Structure-Activity Relationship of Nondioxin-Like PCBs Evaluates and Supports Modeling Predictions and Identifies Picomolar Potency of PCB 202 Towards Ryanodine Receptors. R835432 (2016)
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    Journal Article Chen H, Streifel KM, Singh V, Yang D, Mangini L, Wulff H, Lein PJ. From the cover: BDE-47 and BDE-49 inhibit axonal growth in primary rat hippocampal neuron-glia co-cultures via ryanodine receptor-dependent mechanisms. Toxicological Sciences 2017;156(2): 375-386. R835432 (2016)
    R835432 (Final)
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  • Journal Article Crawley, Jacqueline N; Heyer, Wolf-Dietrich; LaSalle, Janine M. Trends in genetics:TIG. 2016 Mar; Autism and Cancer Share Risk Genes, Pathways, and Drug Targets. R835432 (2016)
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    Journal Article Wilson MD, Sethi S, Lein PJ, Keil KP. Valid statistical approaches for analyzing sholl data: Mixed effects versus simple linear models. Journal of Neuroscience Methods 2017;279: 33-43. R835432 (2016)
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  • Supplemental Keywords:

    Autism, ASD, immune, epigenetics, epigenome, DNA methylation, PBDE, polybrominated diphenyl ethers, pyrethroid, epigenetics, methylome, environmental, genetics, PCB, PBDE, Halopyrroles, DDT, FMR1, RYR, behavior, developmental neurotoxicity

    Relevant Websites:

    Progress and Final Reports:

    Original Abstract
  • 2013 Progress Report
  • 2014 Progress Report
  • 2015 Progress Report
  • 2016 Progress Report
  • 2017 Progress Report