Grantee Research Project Results
2016 Progress Report: The UC Davis Center for Children's Environmental Health and Disease Prevention
EPA Grant Number: R835432Center: 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
Current 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: Hahn, Intaek
Project Period: June 1, 2013 through May 31, 2018 (Extended to May 31, 2019)
Project Period Covered by this Report: June 1, 2016 through May 31,2017
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 , Human 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.
Progress Summary:
Project 1 (Epidemiology and Environment)
To further investigate the copy number variation (CNV) burden variable, we are evaluating different scaling methods. We used different scaling methods on both the duplication and deletion CNV burden variables. Using a 2 standard deviation scale (dividing everything by twice the standard deviation) seemed to perform best. We also tested the approach of dichotomizing the variable by dividing into quartiles and taking the lowest 3 quartiles vs the highest quartile. This way we made the reference categories low CNV burden (bottom 3) and high nutrient for regression and odds ratio calculations. It did make the odds ratios more interpretable, but we saw slightly differing results from the two methods. The other main thing that we did was to separate the iron variable out by month, so we ran 13 different models for each of 3 types of CNV burden, one for each month starting 3 months before pregnancy until 1 month after pregnancy during the breastfeeding period. This was a recommendation because previously they had seen differences between the months. We also looked at just the correlations between CNV and nutrient amount to see if there is any underlying pattern there. The next step will be to look at gene specific burden. We especially want to focus on genes that we have found to be associated with folic acid, iron, prenatal vitamins, and metabolic condition.
PBDEs and early child development:
Laboratory issues including sizable changes in the LOQ’s have delayed the revision of our manuscript reporting PBDE levels in pregnant women from MARBLES. The reviewers were concerned about the small sample size. Because more time has passed, we are able to increase the sample size with children who have now completed the protocol and have their final diagnosis. Over 40 children have been diagnosed with ASD from over 200 who have completed the protocol. We are now sending the maternal samples for the additional children to another lab, this one at the State of California, where Drs. Petreas and Park will conduct the PBDE determinations on the new batch, along with a subset of 20 from the previously analyzed samples.
Pyrethroid pesticides and early child development:
In the MARBLES cohort study, we recently received the final batch of results from Emory University on pyrethroid metabolites in maternal urine from the second and third trimester. A paper is being drafted examining variability over the course of pregnancy using an average of 9-10 individual samples from 10 women. Additionally, analyses are being conducted on cognitive scores from 6 to 36 months and on final 36-month diagnoses, adjusting for confounders, multiple measurements per mother, and multiple samples for each pooled sample. Results similar to our preliminary ones appear to be upheld. An association with deficits in 6-month cognitive scores as well as 6-month AOSI (Autism Observational Scale for Infants) scores was observed in the smaller subset. The full models with a larger set of children, after adjusting for specific gravity of the urine sample, maternal BMI and periconception vitamin use, birth year, home ownership status and average TCPy (a metabolite of chlorpyrifos) concentrations during the pregnancy, as well as for the sampling design, demonstrate deficits at 6 months of age in gross motor, and also show suggestive associations with lower scores on the composite cognitive function and on fine motor skills also at 6 months of age. None of these associations were retained at ages 12, 24, and 36 months.
Gene by environment interaction – impacts of prenatal exposures on gene expression in children at ages 2-5:
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In collaboration with Dr. Dan Campbell at University of Southern California, more extensive analyses were conducted on RNAseq data obtained on 296 CHARGE children. Building upon earlier work that was presented at ISEE and SER, further quality control was conducted using DESeq2, which provides a more accurate identification of outliers than older software. Thus, we repeated RNAseq alignment and after excluding outliers, analyzed data from 78 TD; 71 DD; and 147 ASD children, for whom indoor pesticide exposure was available. DESeq2 was used to identify differentially expressed genes comparing those exposed vs. not exposed to indoor pesticide applications in 6 or more months of pregnancy. As this package allows for multivariate control of covariates, we adjusted for sex and age in all of the analyses. Because Dr. Campbell’s time was pulled away due to events within his institution, the manuscript has been delayed, but work has resumed.
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An additional analysis focused on examining maternal metabolic conditions during pregnancy in relation to the RNAseq in 305 CHARGE children. Analysis was performed using the Bioconductor package edgeR. KEGG pathway enrichment analyses were performed using Wilcoxon rank sum tests on p-value ranks. Top differentially expressed genes in children with ASD born to mothers with metabolic diagnoses were involved in diverse molecular functions, including neuronal signaling, cell cycle regulation, and immunity. Notable enriched KEGG pathways included chemokine signaling, glutamatergic and dopaminergic synapses, focal adhesion and cytokine-cytokine receptor interaction. A manuscript was drafted, circulated among co-authors, and is being revised prior to submission.
Using the CHARGE Study Exposome for broad screening of factors associated with phenotypic measurements:
Major headway has been made on numerous domains related to the Exposome component of the study (Aim 5). This includes maternal smoking, household second-hand-smoke, marijuana and other recreational drugs, household products including paint, solvents, pesticides, pet products, pets, anti-microbials, and mother’s medical history including medical conditions, and medications.
Project 2 (Perinatal Epigenetic Signatures of Environmental Exposures)
The major objectives to date are to sequence and bioinfomatically analyze MethylC-seq data from MARBLES, understand transcriptional regulation of FOXP3 through DNA methylation, and to determine the most effective current sequencing strategy for genomic DNA from MARBLES samples to identify structural variants once all MARBLES samples are obtained. Dr. LaSalle’s lab has isolated DNA and prepared MethylC-seq libraries from 54 MARBLES cord blood samples, including 26 typical and 26 ASD. WGBS and bioinformatics analyses were performed on all 52 samples. DNA methylation analysis of FOXP3 and a putative enhancer of FOXP3 was performed in sorted cord blood samples from the Ashwood lab and DNA isolated from cell pellets of CHARGE sample ex vivo PBDE treatments from the Van de Water lab. DNA from cord blood samples in undergoing whole genome sequencing on the Illumina X-ten at NovaGene.
Significant Results
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A preliminary analysis of the first 22 samples analyzed by MethylC-seq reveal some regions of differential methylation between typical and ASD samples that will be explored in greater detail when sequencing of all samples is completed (Figure 1).
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MethylC-seq analysis of sorted T regulatory cells reveals preliminary indication of global hypomethylation in addition to FOXP3 that may be useful in estimating the percentage of this cell population from whole cord blood MethylC-seq data (Figure 2).
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MethylC-seq data from MARBLES placental samples were analyzed in univariate and multivariate models for associations with demographic, diagnostic, and self-reported environmental factors. Pesticides were the strongest predictors of methylation. Manuscript is being drafted and results were presented at the Feb 2016 Epigenomics Meeting in Puerto Rico.
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MARBLES placenta MethylC-seq data were analyzed in univariate and multivariate models for associations with PCB and PBDE levels measured by the Analytic core. No significant associations were observed with PBDE congeners, but several significant associations were observed between placental DNA methylation and PCBs (Table 1). PCB 175 was associated with a significantly higher proportion of the placental methylome in PMDs after FDR correction (p=0.01). After adjustment for PMD methylation, PCB 136 was significantly associated with higher HMD methylation (p=0.002).
Project 3 (Immune Environment Interactions and Neurodevelopment)
We examined the effect of sex on immune function in typically developing male and female controls. PBMCs were harvested from children 2-5 years of age with autism spectrum disorder (ASD) and typically developing (TD) age-matched control children enrolled in CHARGE (Childhood Autism Risks from Genetics and the Environment), a population-based case-control study. PBMCs were pretreated for 4 hours with BDE-49 (50 or 250nM) and subsequently tested for innate immune activation with lipopolysaccharide (LPS). Following challenge with LPS, PBMCs isolated from TD boys produced significantly higher levels of the pro-inflammatory innate cytokines/chemokines, IL-1α and IL-8 compared to TD girls. Following concomitant challenge with BDE-49 and LPS, TD boys produced significantly higher levels of additional cytokines/chemokines including IL-10, IL-12p40, MIP-1α and MCP-1 compared to TD girls (Figure 1). In contrast, no sex differences were observed in the ASD group or between sexes for diagnostic groups. These results provide evidence that a highly active BDE congener, relevant to human exposure, is capable of altering the innate immune response in a sex dependent manner in a typically developing pediatric population, but not in children with ASD. We have analyzed maternal plasma/chemokine levels during gestation as well as following PBMC ex vivo BDE49 exposure. Finally, we are actively working on the mTOR analysis via PCR. The goal is to compare expression level of a particular gene amongst ASD and GP samples. Currently, we have 53 samples each with 500ng of RNA prepared and all 53 samples have been run by qPCR for the three housekeeping genes and 8 genes of interest (Table 2). We are currently waiting for the data to be analyzed in the coming month. Further, The integration of projects 3 and 4 has resulted in efforts to create a human neuronal stem cell system to allow testing of cytokines/chemokines during development.
Project 4 (Calcium Signaling Defects in Autism)
Project 4 has used neuronal cell culture models from humans and mice with and without expression of FMR1 CGG expansion repeats, the most prevalent monogenic risk factor for ASDs and the cause of both FXS (full mutation) and the late onset degenerative disorder FXTAS. Studies that have been performed include: single cell and network electrophysiology, Ca2+ imaging, and measures of ROS, and mitochondrial function. Additional studies had investigated morphological endpoints related to activity dependent dendritic growth using immunofluorescent labels targeting specific proteins of interest. Environmental compounds that are actively being studied include: Polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs), bisphenol A (PBA), tetrabromobisphenol A, and chlorpyrifos. Experiments were also performed on ex vivo tissues from the knockin mouse model of FMR1 premutation.
The Pessah lab has completed an exhaustive comparative analysis using isogenic iPSC derived neuronal cultures from a mosaic human premutation patient and tissues and neuronal cultures obtained from the FMR1 premutation mouse (Robin et al., 2017). In brief, the key findings identify abnormal Ca2+-dependent signaling pathways linking abnormal µCalpain, oxidative stress, and glutamatergic neurotransmission with long-term up-regulation of the Cdk5/ATM involved in the DNA Damage Response (DDR) in both the human and mouse models. We concluded that chronic Ca2+ dysregulation amplifies Cdk5-ATM signaling, possibly linking impaired glutamatergic signaling and DDR to neurodegeneration in preCGG brain, thereby establishing a useful gene X environment susceptibility model to test environmental chemicals of interest to the UC Davis Center. Using these models, we are completing a study investigating the differential responses of premutation neurons to the exemplary neurotoxic PCB 95. We found that both FMR1 premutation males and females show responses to PCB 95 that differ from respective WT control neurons at concentrations as low as 1 pM. Importantly there are significant sex differences in the concentration-effect relationship. These results identify FMR1 premutation as a genetic susceptibility to nondioxin-like PCBs through ryanodine receptor-dependent mechanisms, and therefore, may have significant impact on understanding how environmental exposure to POPs may magnify onset and severity of the most common monogenic risk factors for ASDs.
In a related study, we completed an extended structure–activity relationship of nondioxin-like PCBs towards RyR1, which evaluated and further supported modeling predictions from QSAR modeling. Importantly we discovered that the most active PCBs in receptor binding studies are orders of magnitude more potent when assessed using single channel electrophysiology. For example, PCB 202 activates single channel open probability with picomolar potency (Holland et al., 2017), further supporting previous work on the potency of noncoplanar PCBs towards altering activity-dependent growth through an RyR-dependent mechanism, reported by the Lein Lab. As a follow-up, we have submitted a manuscript comparing the relative potency of racemic and separated PCB 95 atropisomers on RYR1, RyR2, and the RyR mixture found in brain tissue (Feng et al 2017).
Finally, Bisphenol A (BPA) and its brominated derivative tetrabromobisphenol A (TBBPA) are high production volume chemicals used in the manufacture of various consumer products. Although regarded as endocrine disruptors, and therefore a concern to developmental health, these chemicals are also suspected to exert nongenomic actions on muscle and brain function that are not well understood. Using skeletal muscle microsomes, we examined the effects of BPA and TBBPA on ryanodine receptor type 1 (RyR1), dihydropyridine receptor (DHPR), and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA). We assessed the impact of these chemicals on Ca2+ dynamics and signaling in embryonic skeletal myotubes through fluorescent Ca2+ imaging and measurement of resting membrane potential (Vm) (Zhang and Pessah 2017). TBBPA activated RyR1 and inhibited DHPR and SERCA, inducing a net efflux of Ca2+ from loaded microsomes, whereas BPA exhibited little or no activity at these targets. Regardless, both compounds disrupted the function of intact myotubes. TBBPA diminished and eventually abrogated Ca2+ transients, altered intracellular Ca2+ equilibrium, and caused Vm depolarization. For some cells, BPA caused rapid Ca2+ transient loss without marked changes in cytosolic and sarcoplasmic reticulum Ca2+ levels, likely owing to altered cellular excitability as a result of BPA-induced Vm hyperpolarization. BPA and TBBPA both interfere with skeletal muscle function through divergent mechanisms that impair excitation-contraction coupling and may be exemplary of their adverse outcomes in other muscle types.
The Lein lab has validated a high content imaging approach for assessing the differentiation of the human LUHMES neuronal cell line. Studies have been initiated to screen cytokine profiles associated with autistic versus neurotypical children as identified in Project 3 and the MARBLES PCB mix, based on PCB congener profiles identified in MARBLES mothers by Core C. In addition, the Lein laboratory has been refining culture conditions for the differentiation of human neural crest stem cells into sympathetic neurons. The Lein lab has extended studies characterizing the effects of ortho-substituted PCBs on the mTOR signaling pathway in neurons, and completed studies of PBDE effects on neuronal morphogenesis in vitro. Both are significant findings and were presented at the March 2017 annual Society of Toxicology meeting in New Orleans, LA. A manuscript describing the PBDE findings was recently published in Toxicological Sciences and a manuscript describing the PCB study is being prepared for submission to Environmental Health Perspectives.
We have now measured cytokine/chemokine levels in supernatants from cells taken during pregnancy (MARBLES) with and without BDE 49 exposure. In addition, we have measured plasma cytokine levels taken throughout pregnancy. We are currently analyzing these data in terms of outcome of the offspring. We have 156 children for whom a final diagnosis has been determined.
Future Activities:
- PBDEs and early child development: Once the laboratory determinations of PBDEs are completed for the new batch of mothers, analyses of the PBDE-child diagnosis associations will be conducted, and the manuscript revised and resubmitted.
- Pyrethroid pesticides and early child development: Two additional manuscripts will be completed on maternal pesticide metabolites measured repeatedly during pregnancy in relation to child cognitive and diagnostic outcomes. The first manuscript will demonstrate the variability in measurements across pregnancy and discuss implications for sampling short-lived compounds in the context of pregnancy. This will be submitted probably to an exposure science journal. The second will report the final analyses, adjusting for confounding and for the sampling design including multiples and pooled samples within a trimester for each mother, of the associations between pyrethroid metabolites and child outcomes in the first three years of life. Depending on the strength of the results, we will select a journal in environment, epidemiology, autism or pediatrics.
- Gene expression in children at ages 2-5:
- Prenatal pesticide exposures: The analyses are completed and a draft manuscript will be completed, circulated among co-authors, and submitted for publication.
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- Maternal metabolic conditions: A manuscript has been drafted describing the gene ontology pathways that are upregulated in children whose mothers had one or more metabolic conditions of obesity, diabetes during pregnancy (gestational or type 2 prior to pregnancy) or hypertension during pregnancy. It will be finalized and submitted for publication.
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- CHARGE Study exposome analyses: In collaboration with Drs. Ritchie, Kim, Selleck, exposome analyses will be conducted in discovery mode using a range of annotation files and methods developed by Dr. Ritchie. A manuscript will be drafted for submission to a peer reviewed publication.
Journal Articles: 137 Displayed | Download in RIS Format
| Other center views: | All 139 publications | 137 publications in selected types | All 137 journal articles |
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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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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) R835432 (2015) |
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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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Bal-Price A, Lein PJ, Keil KP, Sethi S, Shafer T, Barenys M, Fritsche E, Sachana M, Meek MEB. Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity. NeuroToxicology 2017;59:240-255. |
R835432 (2015) |
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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. |
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Barkoski J, Philippat C, Tancredi D, Schmidt R, Ozonoff S, Barr D, Elms W, Bennett D, Hertz-Picciotto I. In utero pyrethroid pesticide exposure in relation to autism spectrum disorder ASD and other neurodevelopmental outcomes at 3 years in the MARBLES longitudinal cohort. ENVIRONMENTAL RESEARCH 2021;194(110495). |
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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.). |
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Bennett D, Calafat A, Hertz-Piccioltto I, Shin H, Tancredi D. Modeled prenatal exposure to per-and polyfluoroalkyl substances in association with child autism spectrum disorder:A case-control study. Enviornmenal Research 2020;186(109514). |
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Bennett D, Bgang S, Kannan K, Parsons P, Takazawa M, Palmer C, Schmidt R, Doucette J, Schweitzer J, Gennings C, Hertz-Picciotto I. Environmental exposures to pesticides, phthalates, phenols and trace elements are associated with neurodevelopment in the CHARGE study. ENVIRONMENT INTERNATIONAL 2022;161(10705). |
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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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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. |
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Breen M, Garg P, Tang L, Mendonca D, Levy T, Barbosa M, Arnett A, Kurtz-Nelson E, Agolini E, Battaglia A. Episignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype. American Journal of Human Genetics 2020;107(3):555-563. |
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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, 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) R835432 (2017) R835442 (2017) |
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Bruce M, Streifel K, Boosalis C, Heuer L, Gonzalez E, Li S, Harvey D, Lein P, Va de Water J. Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain. JOURNAL OF NEUROINFLAMMATION 2019;16(1):200. |
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Bruce M, Hones K, Vernon A, Silverman J, Crawley J, Ellegood J, Lerch J, Va de Water J, Hertz-Picciotto I. Sexually dimorphic neuroanatomical differences relate to ASD-relevant behavioral outcomes in a maternal autoantibody moe model. MOLECULAR PSYCHIATRY 2021;26(12):7530-7537. |
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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. |
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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. |
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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. |
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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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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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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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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 (2015) R835432 (2016) |
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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. <PLosOne 2017;12(1):e0170129. |
R835432 (2016) R835432 (Final) R829388 (Final) R833292 (Final) |
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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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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) R833292 (2012) |
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Choi J, Oh J, Bennett D, Kannan K, Tancredi D, Miller M, Schmidt R, Shin H. Gestational exposure to organophosphate esters and autism spectrum disorder and other non-typical development in a cohort with elevated familial likelihood. ENVIRONMENTAL RESEARCH 2024;263 |
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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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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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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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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. |
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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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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.). |
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Hart L, Thigpen A, Willits N, Lyons L, Hertz-Picciotto I, Hart B. Affectionate Interactions of Cats with Children Having Autism Spectrum Disorder. FRONTIERS IN VETERINARY SCIENCE 2018;5(39). |
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Hennebelle M, Morgan R, Sethi S, Zhang Z, Chen H, Grodzki A, Lein P, Taha A. Linoleic acid-derived metabolites constitute the majority of oxylipins in the rat pup brain and stimulate axonal growth in primary rat cortical neuron-glia co-cultures in a sex-dependent manner. JOURNAL OF NEUROCHEMISTRY 2020;152(2):195-207. |
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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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Keil KP, Lein PJ. DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? |
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Keil KP, Sethi S, Wilson MD, Chen H, Lein PJ. In vivo and in vitro sex differences in the dendritic morphology of developing murine hippocampal and cortical neurons. Scientific Reports 2017;7(1):8486 (15 pp.). |
R835432 (2017) |
Exit Exit |
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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) |
Exit |
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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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Kim D, Shin H, Bgang S, Barr D, Panuwet P, Schmidt R, Hertz-Picciotto I, Bennett D. Temporal Trends of Phenol, Paraben, and Triclocarban Exposure in California Pregnant Women during 2007-2014. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2021;55(16):11155-11165. |
R835432 (Final) |
Exit Exit |
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Kim D, Krakowiak P, Meltzer A, Hertz-Picciotto I, Van de Water J. Neonatal chemokine markers predict subsequent diagnosis of autism spectrum disorder and delayed development. BRAIN BEHAVIOR AND IMMUNITY 2022;100:121-133. |
R835432 (Final) |
Exit Exit |
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Kim K, Bennett D, Calafat A, Hertz-Piccioltto I, Shin H. Temporal trends and determinants of serum concentrations of per-and polyfluoroalkyl substances among Northern California mothers with a young child, 2009-2016. Enviornmenal Research 2020;186(109491). |
R835432 (Final) |
Exit Exit |
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Koenig CM, Lango J, Pessah IN, Berman RF. Maternal transfer of BDE-47 to offspring and neurobehavioral development in C57BL/6J mice. Neurotoxicology and Teratology 2012;34(6):571-580. |
R835432 (2013) R833292 (2012) |
Exit Exit Exit |
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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) |
Exit |
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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) R835432 (2015) |
Exit Exit |
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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) |
Exit |
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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) |
Exit Exit Exit |
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LaSalle JM. Autism genes keep turning up chromatin. OA Autism 2013;1(2):14. |
R835432 (2013) |
Exit Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit |
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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) |
Exit Exit Exit |
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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) R833292 (2012) |
Exit Exit Exit |
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Lopez S, Dunaway K, Islam M, Mordaunt C, Ciernia A, Meguro-Horike M, Hornike S, Segal D, LaSalle J. UBE3A-mediated regulation of imprinted genes and epigenome-wide marks in human neurons. EPIGENETICS 2017;12(11):982-990. |
R835432 (Final) |
Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit Exit Exit |
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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) R835432 (2014) |
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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) R835432 (2015) |
Exit Exit |
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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) R835432 (2015) |
Exit Exit Exit |
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Matelski L, Van de Water J. Risk factors in autism: thinking outside the brain. Journal of Autoimmunity 2016;67:1-7. |
R835432 (2015) |
Exit Exit |
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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) R835432 (2015) |
Exit Exit Exit |
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Mclellan J, Iosif A, Cichewicz K, Canales C, Rahbarian D, Corea M, Bauman M, Nord A, van de Water J. Gestational autoantibody exposure impacts early brain development in a rat model of MAR autism. WATER 2025;. |
R835432 (Final) |
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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) |
Exit Exit Exit |
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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) R833292 (2012) R833292 (Final) |
Exit Exit Exit |
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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) |
Exit Exit |
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Oh J, Bennett D, Calafat A, Tancredi D, Roa D, Schmidt R, Hertz-Picciotto I, Shin H. Prenatal exposure to per-and polyfluoroalkyl substances in association with autism spectrum disorder in the MARBLES study. Enviornmenal International 2020;(106328). |
R835432 (Final) R829388 (Final) R829389 (Final) R833292 (Final) |
Exit Exit |
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Oh J, Shin H, Kannan K, Busgang S, Schmidt R, Schweitzer J, Hertz-Picciotto I, Bennett D. Childhood exposure to per- and polyfluoroalkyl substances and neurodevelopment in the CHARGE case-control study. ENVIRONMENTAL RESEARCH 2022;215(2):114322 |
R835432 (Final) |
Exit |
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Oh J, Bennett D, Tancredi D, Calafat A, Schmidt R, Hertz-Picciotto I, Shin H. Longitudinal Changes in Maternal Serum Concentrations of Per-and Polyfluoroalkyl Substances from Pregnancy to Two Years Postpartum. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2022;56(16):11449-11459. |
R835432 (Final) R829388 (Final) |
Exit Exit |
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Oh J, Shin H, Kannan K, Calafat A, Schmidt R, Hertz-Picciotto I, Bennett D. Per- and Polyfluoroalkyl Substances (PFAS) in Serum of 2 to 5 year-Old Children: Temporal Trends, Determinants, and Correlations with Maternal PFAS Concentrations. ENVIRONEMTAL SCIENCE & TECHNOLOGY 2024;58(9):3151-3162 |
R835432 (Final) |
Exit |
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OH J, Schweitzer J, Buckley J, Upadhyaya S, Kannanm K, Herbstman J, Ghassabian A, SChmidt R, Herts-Picciotto, Bennett D. Early childhood exposures to phthalates in association with attention-deficit/hyperactivity disorder behaviors in middle childhood and adolescence in the ReCHARGE study. INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH 2024;259(114377) |
R835432 (Final) |
Exit |
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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) R831540 (Final) |
Exit Exit Exit |
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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) R829388 (Final) R833292 (Final) |
Exit Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit Exit Exit |
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Powell WT, LaSalle JM. Epigenetic mechanisms in diurnal cycles of metabolism and neurodevelopment. Human Molecular Genetics 2015;24(R1):R1-R9. |
R835432 (2015) |
Exit Exit Exit |
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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) |
Exit Exit |
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Ramirez-Celis A, Edmiston E, Schauer J, Vu T, Van de Water J. Peptides of neuron specific enolase as potential ASD biomarkers:From discovery to epitope mapping. BRAIN BEHAVIOR AND IMMUNITY 2020;84:200-208. |
R835432 (Final) |
Exit Exit |
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Ramirez-Celis A, Becker M, Nuno M, Schauer J, Aghaeepour N, Van de Water J. Risk assessment analysis for maternal autoantibody-related autism MAR-ASD:a subtype of autism. MOLECULAR PSYCHIATRY 2021;26(5):1551-1560. |
R835432 (Final) |
Exit Exit |
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Ramirez-Celis A, Croen L, yoshida C, Alexeeff S, Schauer J, Yolken R, Ashwood P, Van de Water J. Maternal autoantibody profiles as biomarkers for ASD and ASD with co-occurring intellectual disability. MOLECULAR PSYCHIATRY 2022;13(6):1098. |
R835432 (Final) |
Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit |
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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) R829388 (Final) R833292 (Final) |
Exit Exit Exit |
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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) R829388 (Final) R833292 (Final) |
Exit Exit Exit |
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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) R829388 (Final) R833292 (Final) |
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Schroeder DI, LaSalle JM. How has the study of the human placenta aided our understanding of partially methylated genes? Epigenomics 2013;5(6):645-654. |
R835432 (2013) |
Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit Exit Exit |
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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) R833292 (2012) R833292 (Final) |
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Shin H, Oh J, Kim K, Bgang S, Barr D, Panuwet P, Schmidt R, Hertz-Picciotto I, Bennett D. Variability of Urinary Concentrations of Phenols, Parabens, and Triclocarban during Pregnancy in First Morning Voids and Pooled Samples. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2021;55(23):16001-16010. |
R835432 (Final) |
Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit Exit |
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Van de Water J, Jones K, Silverman J, Yang M, Crawley J. Autism-Specific Maternal Autoantibodies Produce ASD Relevant Behaviors in a Moe Model. BIOLOGICAL PSYCHIATRY 2018;83(9):S147-S148. |
R835432 (Final) |
Exit Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit Exit Exit |
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Walter K, Lin Y, Kass P, Puschner B. Association of Polybrominated Diphenyl Ethers PBDEs and Polychlorinated Biphenyls PCBs with Hyperthyroidism in Domestic Felines, Sentinels for Thyroid Hormone Disruption. BMC VETERINARY RESEARCH 2017;13(120). |
R835432 (Final) |
Exit Exit |
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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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Wayman GA, Yang D, Bose DD, Lesiak A, Ledoux V, Bruun D, Pessah IN, Lein PJ. PCB-95 promotes dendritic growth via ryanodine receptor-dependent mechanisms. Environmental Health Perspectives 2012;120(7):997-1002. |
R835432 (2013) R833292 (2012) R833292 (Final) |
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Zerbo O, Qian Y, Yoshida C, Grether JK, Van de Water J, Croen LA. Maternal infection during pregnancy and autism spectrum disorders. Journal of Autism and Developmental Disorders 2015;45(12):4015-4025. |
R835432 (2015) |
Exit Exit |
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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) |
Exit Exit Exit |
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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) |
Exit Exit |
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Zhu Y, Gomez J, Laufer B, Mordaunt C, Mouat J, Soto D, Dennis M, Benke K, Bakulski K, Dou J, Marathe R, Jianu J, Williams L, Fugon O, Walker C, Ozonoff S, Daniels J, Grosvenor L, Volk H, Feinberg J, Fallin M, Hertz-Picciotto I, Schmidt R, Yasui D, LaSalle J. Placental methylome reveals a 22q13.33 brain regulatory gene loc associated with autism. GENOME BIOLOGY 2022;23(1):46-56 |
R835432 (Final) |
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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) |
Exit Exit |
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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 (2015) |
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Saldarriaga, Wilmar; Lein, Pamela; González Teshima, Laura Yuriko; Isaza, Carolina; Rosa, Lina; Polyak, Andrew; Hagerman, Randi; Girirajan, Santhosh; Silva, Marisol; Tassone, Flora. Neurotoxicology. 2016 Mar;Phenobarbital use and neurological problems in FMR1 premutation carriers. |
R835432 (2015) R835432 (2016) |
Exit Exit Exit |
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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) |
Exit Exit |
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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) |
Exit Exit |
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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 |
R835432 (Final) |
Exit Exit |
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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) |
not available |
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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) |
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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) |
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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) |
not available |
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Edmiston, Elizabeth; Ashwood, Paul; Van de Water, Judy . Biological psychiatry. 2017 Mar 01; Autoimmunity, Autoantibodies, and Autism Spectrum Disorder. |
R835432 (2016) |
not available |
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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) |
Exit Exit |
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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) |
not available |
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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) |
not available |
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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) |
not available |
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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. |
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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. |
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Keil KP, Lein PJ. DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders?. Environmental Epigenetics 2016;2(1). |
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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. |
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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. |
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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. |
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Matelski, Lauren; Van de Water, Judy. Journal of autoimmunity. 2016 Feb; Risk factors in autism:Thinking outside the brain. |
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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. |
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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. |
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Vogel Ciernia, Annie; LaSalle, Janine. Nature reviews. Neuroscience. 2016 07; The landscape of DNA methylation amid a perfect storm of autism aetiologies. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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Progress and Final Reports:
Original AbstractThe 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.