Grantee Research Project Results
2014 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, 2014 through May 31,2015
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, the California Department of Health Services, and the broader cross-cultural community, in both the research process and the translation and application of our research findings.
Progress Summary:
Project 1 (Epidemiology and Environment). Analyses from the CHARGE study demonstrated that exposures to elevated ozone during gestation in combination with a high burden of DNA duplications was associated with an especially strong odds ratio for ASD vs. typical development. In general, many combinations of air pollutant exposures with CNV metrics showed relationships consistent with multiplicative and/or additive interactions.
In preliminary data on a subset of the MARBLES cohort study participants, second and third trimester urinary metabolites of pyrethroid insecticides were associated with elevated risk for developmental delay by 36 months of age. The number of cases with ASD in this preliminary dataset was too small for a sufficiently powered analysis.
Among 128 ASD CHARGE children for whom RNAseq analyses were completed, 32 genes were differentially expressed in exposed vs. unexposed (unadjusted p<0.001; Bonferroni-adjusted p<0.10). All but one was up-regulated in the pesticide-exposed group, and one quarter were found in annotated toxico- and pharmaco-genomic databases to be associated with organophosphate (OP) pesticides. Of the top 10, 2 have been associated with thyroid dyshormonogenesis and 2 with Parkinson’s Disease. In contrast, among 65 TD controls, only 8 differed significantly by pesticide exposure or associated with other pesticides in annotated databases. Differential patterns in cases vs. controls for prenatal pesticide-associated gene expression suggest ASD-relevant gene-environment interactions. As few organophosphates are still present in household products in the United States, common toxicologic mechanisms shared by OPs and pyrethroids are relevant. Several modes of interaction, including pesticide-induced epigenetic changes on a pathway of brain development and a reverse causation where neurodevelopmental susceptibility influences sensitivity to pesticide activity, must be considered.
Project 2 (Perinatal Epigenetic Signatures of Environmental Exposures). The major activities from Dr. LaSalle’s laboratory 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 analyses of Aim 1. We examined transcriptional regulation of the FOXP3 locus by DNA methylation. An upstream promoter or enhancer of FOXP3 was identified and both FOXP3 promoter methylation and transcription were found to be sensitive to the DNA methylation inhibitor 5 Aza-C.
Dr. Schmidt has been cleaning existing food frequency questionnaire (FFQ) nutrient data, as well as preparing a new batch of FFQs to ship to NutritionQuest to analyze for MARBLES. She also has been cleaning existing data on serum folate, vitamin B12, and choline measurements, and started to run descriptive analyses in preparation for operationalizing these variables as exposures of interest. They then will be examined in relation to CNV burden, total % methylation, and repetitive % methylation. Prenatal vitamin use in the first month of pregnancy was shown to have a 4-fold protective effect in MARBLES. Further, global DNA methylation measured by LINE-1 pyrosequencing positively correlated with folic acid levels in pregnancy month 1.
Project 3 (Immune Environment Interactions and Neurodevelopment). Maternal sample profiles from Core C currently are under analysis by Core C and Project 1. We have collected samples for analysis and now are analyzing the samples for their cytokine/chemokine profiles. We have 50% of the samples completed. We have determined the primers needed for RT-PCR of the samples for mTOR signaling pathway mRNA determination to be ready for Year 3. We have received data from the analysis of samples for PBDE from Core C and are using these data in preparation of two manuscripts. We have analyzed cytokine/chemokine levels in the plasma and activated immune cells from children in CHARGE. One paper from these data has just been published (Akintunde ME, Rose M, Krakowiak P, Heuer L, Ashwood P, Hansen R, Hertz-Picciotto I, Van de Water. J. Neuroimmunol. 2015 Sep 15;286:33-41. doi: 10.1016/j.jneuroim.2015.07.003) and the second paper is in preparation. With Project 4, we are refining the culture conditions for neural crest stem cells for use in future studies, and have brought in LUHMES neuronal cell line for cytokine and exposure studies. Working with Project 1, we have analyzed data from Core C on PBDE levels as they correlate with immune function in children from the CHARGE study. These findings are very exciting and currently in preparation for publication.
Total body burden for PBDEs in a pediatric population. Our first analysis was done in the typically developing pediatric population that was part of the larger CHARGE study. We examined the effect of sex on body burden of PBDEs, PCBs, and how this relates to immune function in typically developing male and female controls. Working with Core C, we determined no significant difference in total lipid levels in the plasma between all males and females within this study was observed. We did note, however, that there was a significant increase in PCB in females when compared to males.
For the total pediatric population, we examined the immune response following stimulation of the innate immune system with LPS. There were no significant differences between males and females at baseline or following LPS stimulation alone. However, we found that following ex vivo exposure of peripheral blood mononuclear cells to BDE-49, exposure to 50 nM of BDE-49 alone decreased production of the Th2 cytokine IL-13. When peripheral blood cells are pre-incubated with BDE-49, then challenged with LPS to activate innate immune cells, there was a marked difference between the boys and girls in the effects of BDE on the innate immune response. There was a great deal more variability in the immune response of the male subjects compared to the females following BDE-49 exposure. Although we are aware that the number of female subjects is very small (these are TD children from CHARGE enrolled at a 4:1 male:female ratio), the data are compelling and provide support for a closer examination of the differences between male and female children in their response to environmental toxicants.
Project 4 (Calcium Signaling Defects in Autism). We have successfully isolated isogenic pairs of fibroblasts obtained from two unrelated full mutation individuals (225 and 320 CGG repeats), as well as two unrelated individuals in the high premutation range (160 and 170 CGG repeats). This has required extensive subcloning of fibroblasts to separate and identify isogenic populations from the same (mosaic) individual by testing for which allele, normal or expanded, remains active. From isogenic fibroblasts, we dedifferentiated iPSCs using the four-factor method described in the original proposal. iPSCs derived by this method were tested for stem cell markers and pushed to neuronal lineage as we previously reported for the mid-premutation (94 CGG repeats) study published in 2012 (Cao, et al., 2012). Neuronal precursor lines have been expanded and cryopreserved (Pessah Lab).
We have continued our molecular and cellular investigations of etiological causes responsible for the early onset abnormalities in neuronal growth and synaptic function that we have identified precede degeneration of the neuronal network. In this regard, the Pessah lab has identified significant new information about involvement of the µ-calpain-Cdk5-ATM signaling pathway that could account for the sequelae of early developmental and later neurodegenerative phases of FMR1-related disorders. These studies have initially focused on the premutation mouse model but have recently expanded to our human iPSC-derived models.
The Lein lab has developed and validated a high content imaging approach for quantifying dendritic morphology and the ratio of excitatory to inhibitory synapses in primary neuronal cell cultures. This will enable a higher, more rapid throughput of screening environmental factors for modulation of these endpoints of neuronal connectivity. The Lein lab also has made progress in characterizing the effects of ortho-substituted PCBs on the mTOR signaling pathway in primary neuronal cell culture derived from rodent models. In parallel with work proceeding in the Pessah lab on human iPSC-derived models, the Lein lab is developing two human neuronal cell culture models to be used for screening effects of cytokines identified in Project 3 on neuronal differentiation and maturation. These two cell models include the LUHMES neuronal cell line and neurons derived from neural crest stem cells isolated from human hair follicles.
Results:
1) Successfully produced five isogenic pairs of isogenic iPSC-derived neuronal precursor cells from human patients in the following ranges: one patient in the mid-premutation (94 CGG repeats), two patients in the high-premutation (170 CGG repeats), and two patients in the full mutation (>200 CGG repeats) range (patients with Fragile X Syndrome). Each of these five lines is paired with its own isogenic line with the FMR1 gene in the normal range (30-40 CGG repeats). The Pessah lab has initiated characterization of these lines and their responses to environmental chemicals of interest.
2) PCB 95 and chlorpyrifos oxon (CPFO) directly target RyR channels with sub- to low-nanomolar potency, but with differing patterns of activity. We have completed concentration-effect curves comparing how PCB 95 and CPFO alter the gating kinetics of reconstituted ryanodine receptor Ca2+ channels under voltage clamp. Both behave as highly potent drugs able to have demonstrable activating influences with thresholds <1 nM and “remarkable” in the 1-100 nM range. However, PCB 95 produces long-lived stabilization of the channel full-open state over the life of the experiment; CPFO produces a unique biphasic action on the channel, first increasing the frequency of gating transitions by >5-fold followed by a collapse of channel activity towards the original baseline activity. The Pessah lab has reported transgenerational effects of environmental PCB exposure to killifish influences long-term expression of RYR-regulated signaling pathways (Fritsch, et al., 2014) and additional evidence of the additivity of PCBs towards RyR activity in salmon muscle (Fritsch and Pessah, 2014). The Pessah lab is completing two additional manuscripts, one focused on PCB x gene interactions, the second on the interaction of CPF and CPFO with the RyR complex.
3) FMR1 premutation brain and neurons have abnormal resting Ca2+, which is associated with both chronic activation of the µ-calpain-p35/p25-Cdk5-ATM pathway – the pathway that regulates expression and phosphorylation of excitatory synaptic proteins – and nuclear DNA Damage Response (DDR). The initial results were presented at the Keystone Symposium on Neurodevelopmental Disorders on March 19, 2015, and a review of the subject has been published (Berman, et al., 2014).
4) The Lein lab has completed an initial study of one of three maternal autism risk antibodies: collapsin response mediator protein 1 (CRMP1). CRMP1 is known to play an important role in neurodevelopment via regulation of axonal guidance and dendritic outgrowth. Axonal and dendritic morphologies are critical determinants of neuronal connectivity, and altered neuronal connectivity is thought to lie at the core of ASD pathogenesis. The Lein lab, in collaboration with the Van de Water lab (Project 3), tested the hypothesis that maternal autoantibodies against CRMP1 (aCRMP1-IgG) contribute to ASD pathogenesis by directly interfering with CRMP1 to alter axonal and/or dendritic growth. Using an in vitro model of primary rat hippocampal and cortical neurons, we have shown that aCRMP1-IgG recognizes CRMP1 in developing hippocampal and cortical neurons, and antibody binding to CRIMP1 does not cause overt cellular toxicity. Preliminary results suggest that exposure of hippocampal neurons to aCRMP1-IgG has no effect on axonal or dendritic length or signaling in these cells.
5) The Lein lab has completed an assessment on the ontogeny of biochemical, morphological and functional parameters of synaptogenesis in primary cultures of rat hippocampal and cortical neurons (Harrill, et al., 2015). Differences and similarities in the ontogeny of synaptogenesis exist between hippocampal and cortical neurons, depending on the biological level examined. Assessment of synaptophysin protein levels by ELISA showed a general increase in synapse formation in both cell types with increasing time in culture, while high-content imaging was able to delineate cell type-dependent differences in formation of excitatory versus inhibitory synapses. The functional significance of differences in the balance of excitatory to inhibitory synapses was confirmed by the assessment of network activity using microelectrode arrays. These results suggest that high-content imaging and microelectrode arrays provide complementary approaches for quantitative assessment of synaptogenesis, which should provide a robust readout of toxicologic and pharmacologic effects on this critical neurodevelopmental event.
Community Outreach and Translation Core. The COTC hosted a joint facilitated meeting for strategic planning in community engagement at the MIND Institute. Participating organizations included the MIND Intellectual and Developmental Disabilities Research Center and the Center of Excellence in Developmental Disabilities. We identified several new community-based organizations/audiences for engaging in CCEH outreach and translation activities. These publicly funded preschools and home visiting programs target low resource, high-risk populations.
The COTC partnered with the Center of Excellence in Neurodevelopmental Disabilities for the annual Summer Institute on Neurodevelopmental Disorders. The event was held at the UC Davis Conference Center on August 8. The COTC hosted a session on environmental contributors to neurodevelopmental disorders. The invited speaker was Elise Miller of the Collaborative on Health and the Environment. All talks from the event, including Ms. Miller’s, were video recorded and now are publicly available on the MIND Institute website (http://www.ucdmc.ucdavis.edu/mindinstitute/videos/video_summerinstitute.html).
On May 19, Robin Hansen and Melissa Rose gave an invited talk for the Early Start Partners Institute, a statewide association of early intervention service providers, family support personnel and managers. They will be giving the same talk on September 27 to the California Infant Development Association’s annual meeting.
Resources and Materials: The COTC developed a comprehensive webpage within the MIND/CCEH website that includes a wide range of resources on children’s environmental health for different audiences. A new brochure on environmental risks to neurodevelopment has been prepared and will be printed soon. We also are working on a Spanish language resource to inform and educate women in the Latino community about the benefits of preconceptional and early prenatal folic acid supplementation. This resource will highlight findings from Center research showing a reduced risk for autism in offspring of women who supplement folic acid in these critical time periods of early brain development. The COTC supports staff in the MIND Institute Resource Center. These staff members are responsible for building and maintaining an area of the Resource Center dedicated to topics in children’s environmental health and environmental risks to neurodevelopment.
Tracking: The COTC tracks all CCEH dissemination activities. Working with the Health System Public Affairs office, the COTC coordinates press releases, and obtains media reports containing quantitative data on CCEH contributions to newspaper, radio, and television coverage.
Analytical Core. Within the last year, Core C developed and validated a number of analytical methods on the instrumentation that were acquired and installed in Years 1 and 2. In particular, we moved the validated GC/MS/MS method for the quantification for PBDEs and PCBs to the Bruker TSQ SCION instrument, and finalized the validation of an LC-MS/MS method for the quantification of OH-PBDEs and OH-PCBs on the EVOQ LC/MS. All methods are able to utilize low-volume plasma samples while reaching low LOQs and LODs. In Years 1 and 2, we analyzed 215 + 269 = 484 maternal plasma samples (from MARBLES) from high-risk mothers for both prototype 13 PBDE and 20 PCB congeners and their hydroxylated metabolites. During this project period, we focused on lipid methodologies for accurate correction of PBDE and PCB congeners on a ng/g lipid basis. Several methods and laboratories were compared side-by-side for the direct determination of total triglyceride and total cholesterol. We subsequently evaluated currently available mathematical formulas to estimate total plasma lipids from total triglyceride and total cholesterol. Careful data analysis, comparison, and re-analysis of matched sample vials revealed that the initial set of 215 samples was contaminated with PCBs and PBDEs. Investigation revealed that contamination occurred during sample extraction, which was performed previously in an older laboratory on campus. Subsequently, another set of 269 plasma was extracted in a clean laboratory environment and analyzed for PBDE (BDE-17, 28, 47, 49, 52, 66, 85, 95, 99, 100, 153, 154, 183) and PCB (PCB-11, 52, 77, 84, 91, 95, 101, 118, 131, 132, 135, 136, 138, 149, 153, 174, 175, 176, 180, 196) congeners. Final data processing for determination of quantitative results is completed and manuscript preparation is underway. In this review period, we also compared and validated multiple sample preparation methods for the extraction and purification of PBDE /PCB congeners in milk samples using bovine milk as a matrix for method optimization. In order to reach the necessary LODs and LOQs, a volume of 5 ml of milk sample was extracted using a modified QuEChERS method, purified by gel permeation chromatography and quantified using gas chromatography-triple quadruple mass spectrometry. Most stored breast milk samples collected throughout the studies are short of the 5 ml sample volume required for analysis. We plan to evaluate method modifications to reduce the required milk volume for extraction.
The Analytical Core also evaluated various enzyme assays for the direct determinations of total triglyceride and total cholesterol. We subsequently evaluated different available algorithms to estimate total plasma lipids from total triglyceride and total cholesterol.
Future Activities:
Individual component plans are described in the sections above and there are no plans that deviate from the activities in the original proposal. As a whole, the Center plans to hold a meeting of the Scientific Advisory Committee in winter 2016. Furthermore, several members from our Center are participating in CEHC workgroups and will continue to do so in the subsequent reporting period.
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? |
R835432 (2015) |
Exit Exit Exit |
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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.
Project Research Results
- Final Report
- 2017 Progress Report
- 2016 Progress Report
- 2015 Progress Report
- 2013 Progress Report
- Original Abstract
137 journal articles for this center