Grantee Research Project Results
2013 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, 2013 through May 31,2014
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.
(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). In this project we initiated analyses of gene-by-environment associations that might play a role in ASD etiology. We prepared a dataset for our collaborators at Penn State who have generated the copy number burden from the CHARGE Study DNA samples, and provided them with four exposure variables: PM10, PM2.5, NO2 and ozone, each measured as an average exposure in four possible time periods: whole pregnancy or each trimester. First, the copy number outcomes were scaled and then normalized. The following three genetic variables were analyzed: overall copy number burden, total duplications, and total deletions, each of which was measured as total length in kbp. The sample consisted of ~300 children aged 2-5 years of age who participated in the CHARGE study, for whom we had air pollution variables and CNV variables, as well as a confirmed diagnosis of either case (full syndrome autism) or control (typical development). We posed two conceptual models of interaction.
In the first, we hypothesized that high exposures to air pollutants might result in de novo changes that manifest as increased variability in copy number—either more deletions or more duplications. Although we are not able to distinguish de novo from inherited CNVs (this will require CNV measurement in fathers and mothers or other family members), an initial examination to see if an association was present would be useful if the answer was in the affirmative, but not informative otherwise, as the ratio of the proportions of inherited to de novo CNVs could be large.
Pairwise correlations were calculated for each of four environmental air pollutants occurring in each of four possible time windows (pregnancy or each trimester), in relation to each of three genetic variables (48 comparisons). These ranged from about -0.098 to 0.108, and none reached a nominal level of 0.05 for significance. The conclusion is that if air pollution is associated with total CNV burden, total duplications or total deletions, it is not strong; however, because we are not able to identify which CNVs arose de novo, we cannot rule out a role for air pollution in altering CNV burden.
In the second conceptualization of gene-by-environment interaction, we hypothesized that the impact of air pollution exposure might be modified according to the underlying CNV burden of the individual. Under this model, the outcome is a diagnosis of autism, with main effects for both the CNV variable and the ambient air pollutant, to which a product term of these two variables is added. By dichotomizing both exposure and CNV burden, we addressed those within the top 25th percentile of exposure who have an elevated CNV burden to determine if their risk with ASD exceeded the mere summary of the two main effects.
The logistic regression model showed no interactions in regard to any modifying effects of total CNV, total duplication load, and total deletion load on the associations between autism and PM10, PM2.5, or NO2, regardless of the time period of exposure. However, for ozone, there was a markedly increased association with ASD risk for those with the greatest CNV burden. In particular, having been exposed to the top quartile of ozone conferred especially strong odds for ASD among those at the highest levels of CNV, while the association was more moderate (present but not as strong) among those with a lower CNV burden. This was true for total CNV and for total duplications, but not for total deletions. It was present for exposures during pregnancy, the first year of life, and the second year of life. By and large, for many combinations of air pollutants and CNV, the effect of joint exposures to high levels of both was consistent with either an additive or multiplicative relationship to an autism diagnosis.
Project 2 (Perinatal Epigenetic Signatures of Environmental Exposures). Our primary objectives in the first year of funding have been to prioritize the cord blood samples based on LINE-1 pyrosequencing measures of global methylation and to optimize library preparation methods prior to initiating the sequencing of MARBLES samples. Major activities in this reporting period have been the identification and DNA isolation from cord blood samples from MARBLES families and the development of sequencing library methodology for the MethylC-seq and genomic sequencing analyses of Aim 1. In addition, a methylation pyrosequencing assay has been developed and FOXP3 methylation assays are being performed on ex vivo T cell cultures from Dr. van de Water’s lab.
Dr. Schmidt has been cleaning existing food frequency questionnaire (FFQ) nutrient data, and has prepared and shipped a new batch of MARBLES FFQs to NutritionQuest to analyze nutrient content. She also has been cleaning existing data on serum folate, vitamin B12, and choline measurements and has run descriptive analyses in preparation for operationalizing these variables as exposures of interest, to examine in relation to CNV burden, total % methylation, and repetitive % methylation.
Project 3 (Immune Environment Interactions and Neurodevelopment). Results from this project demonstrate that there is a significant difference in PHA-stimulated IL-17 levels from baseline in ASD subjects compared to DD (p=0.001) and TD (p=0.001) subjects. No significant difference was observed between DD and TD subjects (p=0.9228). Further, ASD subjects with asthma expressed a significant increased expression of IL-17 compared to TD subjects with asthma (p=0.0191) and TD subjects without asthma (p=0.0185) (manuscript in preparation). Additional results from this project demonstrate that the immune response of children with ASD reacts differentially to PBDE in ex vivo culture exposures and that these differences correlate with worse behavioral scores. For example, higher levels of PBMC produced IL-4 following 50 nM BDE-49 exposure, and is associated with lower cognitive function in ASD subjects where there is an opposite relationship in the TD children.
Project 4 (Calcium Signaling Defects in Autism). Within the last 2 years (commencing the year before the renewal was funded and during the first year of the current project period) our group has presented compelling evidence that FMR1 premutation knock-in mice carrying high-CGG-repeat alleles (170-190 CGG repeats) exhibit very early morphologic functional abnormalities that correspond to subtle behavioral impairments that become apparent early in life and precede evidence of neurodegenerative sequelae. Mice with expansions in the premutation range exhibit modest to moderately elevated FMR1 mRNA and reduced FRMP, both hallmarks of human premutation carriers. Importantly, we have identified similar abnormalities in human iPSC-derived neurons that express FMR1 GG repeat expansions produced from fibroblasts harvested from premutation carriers, which we recently published. Thus, a major accomplishment within the para-renewal period was to define several basic signaling defects that occur in both human and mouse FMR1 premutation neurons that have realigned and catalyzed a new paradigm in basic and clinical research in the FMR1 field; that early cognitive deficits in premutation children occur long before clinical evidence of neurodegeneration is found in older adults.
In addition, several collaborative activities between Project 4 and CCEH Projects 1, 2, and 3 and the Analytical Core have led to joint publications (detailed under significant results, below). Value added spin off projects initiated by Project 4 investigators also have fostered interactive activities that extend beyond the UC Davis CCEH, and results in several joint publications with research teams at University of Washington, Yale, Penn State University, and University of Colorado.
We produced iPSC-derived neurons from isogenic subclones of primary fibroblasts of a female premutation carrier, with each subclone bearing exclusively either the normal or the expanded (premutation) form of the FMR1 gene as the active allele. We showed that neurons harboring the stably-active, expanded allele have reduced postsynaptic density protein 95 expression, reduced synaptic puncta density and reduced neurite length. Importantly, such neurons also were functionally abnormal, with calcium transients of higher amplitude and increased frequency than for neurons harboring the normal-active allele. Moreover, a sustained calcium elevation was found in the premutation neurons after glutamate application. By excluding the individual genetic background variation, we demonstrated neuronal phenotypes directly linked to the FMR1 premutation. Our approach is significant because it demonstrates the first isogenic, X-chromosomal epigenetic model to catalyze studies of gene X environment interactions in one of the most prevalent causes of developmental disorders that also influences aging related neurodegenerative disorders.
Because young FMR1 premutation carriers can develop characteristic physical features and mild cognitive disabilities, in addition to having a high risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) with aging, especially in males, we examined human postmortem FXTAS brains that exhibit the presence of intranuclear inclusions throughout the brain. A significant new finding is that expression levels of the metabotropic glutamate (Glu) receptor 5 and the Glu transporter excitatory amino acid transporter 1 were found to be reduced in the postmortem cerebellum of PM carriers with FXTAS compared with age matched controls, with higher CGG repeat number having greater reductions in both proteins. These data suggest a dysregulation of Glu signaling in premutation carriers, as would be predicted by both our results with iPSC-derived PNC (Liu, et al., 2012) and neurons cultured from the premutation mouse model (Cao, et al., 2012; Cao, et al., 2013) and are likely playing an etiological role in conferring susceptibility to specific types of chemical exposures that influence these same pathways.
Recent evidence confirms that non-dioxin-like PCBs remain a current and significant risk to the developing human brain. Contemporary unintentional sources of NDL PCBs have been identified, most notably commercial paint pigments, and in the past year it was reported that PCB levels in the indoor air of elementary schools in the United States exceed the EPA’s 2009 public health guidelines, and the second most abundant congener identified in indoor school environments was the NDL congener PCB 95. Our investigations demonstrated that PCB 95 promotes dendritic growth and the formation of excitatory synapses in cultured rat hippocampal neurons via ryanodine receptor (RyR)-dependent mechanisms (Wayman, et al., 2012; Lesiak, et al., 2014). PCB 95 activation of RyRs is linked to enhanced dendritic growth by a Ca2+-dependent CaMK1-CREB-Wnt signaling pathway (Wayman, et al., 2012), and to increased synaptogenesis via a CREB-miR132-p250GAP signaling pathway (Lesiak, et al., 2014). These effects of PCB 95 map onto signaling pathways implicated in neurodevelopmental disorders, and likely interact with the calcium signaling defects observed in FMR1 premutation neurons.
Bifenthrin, a relatively stable type I pyrethroid that causes tremors and impairs motor activity in rodents, is broadly used, and current exposures have broad implications on children’s health. However, very little is known about possible mechanisms mediating developmental neurotoxicity of bifenthrin (and other pyrethroids) at low exposure levels. We investigated whether nanomolar bifenthrin alters synchronous Ca2+ oscillations (SCOs) necessary for activity-dependent dendritic development. Using primary mouse cortical neurons, we discovered that acute exposure to low nM bifenthrin rapidly increased the frequency of SCOs by nearly 3-fold and decreased SCO amplitude. Changes in SCO properties were independent of modifications in voltage-gated sodium channels because 100 nM bifenthrin had no effect on the whole-cell Na+ current, nor did it influence neuronal resting membrane potential. Metabotropic glutamate receptor mGluR5 antagonist MPEP normalized bifenthrin-triggered increase in SCO frequency without altering baseline SCO activity, indicating that bifenthrin amplifies mGluR5 signaling independent of Na+ channel modification. Bifenthrin-modified SCO rapidly enhanced the phosphorylation of cAMP response element-binding protein (CREB). Subacute (48 hours) exposure to bifenthrin commenced enhanced neurite outgrowth and persistently increased SCO frequency and reduced SCO amplitude. Bifenthrin-stimulated neurite outgrowth and CREB phosphorylation were dependent on mGluR5 activity because MPEP normalized both responses. Collectively, these data identify a new mechanism by which bifenthrin potently alters Ca2+ dynamics and Ca2+-dependent signaling in cortical neurons that have long-term impacts on neuronal development that are likely to be relevant to heritable impairments we have observed in our FMR1 CGG repeat expansion models discussed above.
Community Outreach and Translation Core. On August 2, 2013, 259 participants attended the Summer Institute on Neurodevelopmental Disorders, directed by COTC Leader, Dr. Robin Hansen. Attendees included educators, parents, physicians, psychologists, other health and allied health professionals, and students. Project 1 Leader, Dr. Irva Hertz-Picciotto gave the keynote address: What Causes Autism? The Role of Environmental Exposures. Dr. Rebecca Schmidt, Project 2 Co-Leader presented a talk, Nutrition and Neurodevelopment: Importance and Potential Mechanisms. Talks from the Summer Institute are available for public download from the MIND Institute website.
On November 7, the COTC convened a meeting of the Community Advisory Council (CAC) The Council is moving forward to contact policy makers regarding the folate findings from the previous funding period (Project 2). In response to input from members of the CAC, a workshop for approximately 100 autism service providers at the Alta California Regional Center was held on February 25, 2014. Drs. Hansen and Angkustsiri presented results from the CHARGE study related to associations between GI symptoms and behavior in CHARGE children. They also presented findings on parental report of Complementary and Alternative Medicine (CAM) treatments in the CHARGE study. The presentation included a review of the evidence related to safety and efficacy for the most commonly reported CAM treatments.
Analytical Core. The Analytical Core has acquired and installed two key instrumentations for all upcoming quantitative analyses. Both instruments are up and running. In this review period, the analytical core developed and validated a GC/MS method for the quantification for PBDEs and PCBs, and OH-PBDEs and OH-PCBs in low-volume plasma samples. We analyzed 215 plasma samples (from MARBLES) from high-risk mothers for those compounds.
We developed and validated a GC/MS method to simultaneously detect select PBDE (BDE-17, 28, 47, 49, 52, 66, 85, 95, 99, 100, 136, 153, 154, 183) and PCB (PCB-11, 84, 91, 95, 101, 118, 131, 132, 135, 136, 138, 149, 153, 174, 175, 176, 180, 196) congeners in plasma (volume for extraction and analysis: 0.5 ml). Samples were collected from 79 women enrolled in MARBLES and for whom longitudinal samples were available throughout gestation and at birth. Multiple linear regression models were used to predict PBDE burdens from mothers' ages, gestational stages, sample collecting time and weight changes during pregnancy. We compared our results to data generated in other studies from various populations (NHANES, CHAMACOS, SF Bay Area) and determined that MARBLES women had higher concentrations of PBDEs during pregnancy compared to all other populations. In addition, patterns in lipid-corrected PBDE levels illustrated the importance of gestational age and enrichment of minor congeners as potential risk factors in the MARBLES cohort.
The analytical core also developed a method for analyzing milk samples from PBDEs and OH-PBDEs. The Core also evaluated various approaches for the determination of total lipids in plasma samples.
Future Activities:
Planned work for the coming period are to:
a) Submit a manuscript on the interactions between child’s copy number burden and exposures to air pollutants during gestation and the first 2 years of life.
b) Conduct broader analyses of interactions between child’s CNV and maternal nutrition in relation to autism diagnosis. The nutrition variables will be broad, including intake of micronutrients, as well as nutrient measurements made in the newborn blood spots.
c) Prepare a grant proposal aimed at assessing copy number burden in each of the parents to identify which segments of copy number variation are de novo, and which are inherited. For those CNV that are inherited, a further analysis will evaluate whether parent of origin is differential by case-control status.
Our plans for the coming year are to accelerate our characterization of the isogenic premutation NPCs we isolated from human iPSC. We will be focusing on critical signaling molecules that interfere with both DNA repair and synaptic development and function. We also will proceed with assessments of differential responses to the environmental chemicals originally proposed in the application.
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. |
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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. |
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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.). |
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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. |
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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.). |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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]. |
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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.). |
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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. |
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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. |
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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) |
Exit |
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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) |
Exit |
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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) |
Exit |
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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. |
R835432 (2016) |
Exit Exit |
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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. |
R835432 (2016) |
Exit Exit |
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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). |
R835432 (2016) |
Exit Exit |
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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. |
R835432 (2016) |
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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.
Project Research Results
- Final Report
- 2017 Progress Report
- 2016 Progress Report
- 2015 Progress Report
- 2014 Progress Report
- Original Abstract
137 journal articles for this center