Final Report: UC Davis Center for Children’s Environmental Health

EPA Grant Number: R833292
Center: UC Davis Center for Children’s Environmental Health
Center Director: Pessah, Isaac N.
Title: UC Davis Center for Children’s Environmental Health
Investigators: Pessah, Isaac N. , Ashwood, Paul , Bennett, Deborah H. , Berman, Robert F. , Golub, Mari S. , Hansen, Robin , Hertz-Picciotto, Irva , Ozonoff, Sally , Van de Water, Judith , Walker, Cheryl
Institution: University of California - Davis
EPA Project Officer: Louie, Nica
Project Period: November 1, 2006 through October 31, 2011 (Extended to October 31, 2013)
Project Amount: $3,782,733
RFA: Centers for Children’s Environmental Health and Disease Prevention Research (2005) RFA Text |  Recipients Lists
Research Category: Health , Children's Health , Health Effects

Objective:

The principal concern of the UC Davis Center for Children's Environmental Health (CCEH) is to identify and understand environmental, immunologic and genetic risk factors contributing to the incidence and severity of childhood autism. Autism is a heterogeneous neurodevelopmental disorder defined by core deficits in social reciprocity, communication, and restrictive/repetitive patterns of interest and behavior (American Psychiatric Association, 2000). The prevalence of autism is approximately four times higher in males than in females. Results from more than 10 genome-wide autism screens indicate that potential susceptibility genes are spread across the entire genome. Interactions among multiple genes are likely to contribute to autism, and epigenetic factors and exposure to environmental modifiers may contribute significantly to variable expression of autism and autism-related traits.

The mission of the CCEH is to promote daily interactions among a multidisciplinary team of scientists whose main research interest is to understand the complex web of etiologic factors that contribute to autism. The shared philosophy among Center participants is that a better understanding of the immunological and neurobiological mechanisms associated with this neurodevelopmental disorder can not only lead to a better understanding of the mechanisms that influence it but can also accelerate the discovery of effective intervention strategies. Since it is generally accepted that the earlier an intervention is begun in autistic children, the greater the chances of improvement, an intervention that can be implemented before symptoms have fully manifested should have the strongest impact in reducing severity and potentially even preventing some cases. Thus, early markers of risk are needed to identify children who are at risk. These may include behavioral, environmental, physiologic, biochemical and genomic markers, and those based on morphological and neuroimaging parameters.

The goals of the CCEH are to: (1) better understand the mechanisms by which environmental, immunologic and molecular factors interact to influence the risk and severity of autism; (2) identify early immunologic, environmental and genomic markers of susceptibility to autism; (3) develop mouse models of immunologic susceptibility to environmental triggers and define the impact of these triggers on the development of complex behaviors, key brain structures and neurotransmitter receptors relevant to autism; (4) translate our research findings into diagnostic tools that can be used in clinical practice to predict early autism risk; and (5) supply the community with accurate and timely information about autism risk factors.

Project 1 (R83329201C001): Environmental Epidemiology

The overall objective of Project 1 was to build upon our discovery of immunologic and molecular biomarkers specific to children with autism found in 2-5 year olds enrolled in the CHARGE (Childhood Autism Risks from Genetics and Environment) Study.

Specific Aim 1

Hypothesis: Children with autism can be distinguished from those without autism by markers of immune dysregulation (at birth, as well as post-diagnosis) and by prenatal, immunologically relevant events and exposures.

Specific Aim 2

Hypothesis: Children with autism can be distinguished from children without autism by their xenobiotic exposures and biomarkers, which in turn are related to immune dysregulation.

Specific Aim 3

Hypothesis: Transcriptional genomic profiles of children with autism differ from those of children without autism.

Specific Aim 4

Hypothesis: The exposure and biomarker (immune, xenobiotic, genomic) differences will be most pronounced for specific phenotypic subsets among children in the CHARGE Study.

Project 2 (R83329201C002): Immunological Susceptibility of Autism

Our aims included the examination of environmental toxicants such as PBDE47 on immune function in children with autism and the identification of the autoantigens in both the maternal population and their offspring. We conducted a longitudinal analysis of children’s immune function parameters and performed B cell function analysis using peripheral blood mononuclear cells (PBMC) from CHARGE-BACK subjects.

Specific Aim 1: To perform longitudinal serologic analyses. We will examine plasma from patients with autism and our control populations for changes in IgG, IgM, IgA and IgE; basal cytokine profile; and leptin levels.

Specific Aim 2.1: To analyze the patterns of peripheral blood cell surface marker expression following stimulation/activation. Cell surface marker expression and cytokine production in stimulated and unstimulated cells will be studied following culture with recall vaccine antigens and mitogens. In addition, culture supernatants will be analyzed by Luminex multiplex analysis for evidence of differential cytokine production.

Specific Aim 2.2: To analyze isolated B cells from patients with autism and controls following incubation with Fab anti-IgM, with and without CD40L, followed by microarray analysis. To assess the innate arm of the B cell response, we will stimulate isolated B cells with unmethylated oligonucleotides (CpG), lipopolysaccharide (LPS), Flu virus and poly I:C to determine the basal and stimulated levels of IgM and IgG and the upregulation of TLRs by real-time PCR. B cells will be labeled with Indo-1, a calcium indicator dye, to assess early intracellular calcium signaling responses following stimulation with anti-IgM antibody by flow cytometry.

Specific Aim 2.3: To identify the differential functional response of peripheral blood cells from autistic children in the presence of low levels of organic mercury and POPs. PBMC proliferative responses and cytokine production will be analyzed in stimulated cultures with and without xenobiotics. PBMC will be cultured in the presence of low doses (1-100 nM) of MeHg, PCB95 or PBDE47 and then challenged with phytohaemagglutinin (PHA) or LPS.

Specific Aim 2.4: To identify how transcriptional signatures differ following immune cell stimulation/activation under the influence of xenobiotics. Cell cultures similar to those outlined in Aim 2.3 will be analyzed for transcriptional differences between patients and controls. Following stimulation, cultured cells will be placed into tubes containing RNA stabilizing reagents. Based on the experiments proposed in Aims 2.1- 2.3, we anticipate that there will be functional, phenotypic and genotypic differences in the PBMC populations of children with autism compared with age-matched controls.

Specific Aim 3.1: To identity relevant antigens may be crucial to understanding both the etiology and the pathology of autism. Therefore, to characterize the targets of the brain-specific autoantibodies found in the sera of patients with autism in our previous studies, we will use 2-D gel analysis, then in-gel digestion of the target bands followed by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometric peptide mass mapping.

Specific Aim 3.2: To characterize the targets of the brain-specific autoantibodies found in the plasma of mothers of autistic children using 2-D gel analysis followed by MALDI-TOF mass spectrometric peptide mass mapping after in-gel digestion of the target bands.

Specific Aim 3.3: To isolate IgG from sera of mothers that have an autistic child and those who do not for testing in a developmental model of autism. In conjunction with Project 3, we will expose mice during early gestation to purified IgG isolated from mothers with reactivity to human fetal brain antigens. Develoment of the mouse AA-IgG model will allow us to evaluate the role of maternal immune dysfunction on neurodevelopmental behaviors relevant to autism.

Project 3 (R83329201C003): Neurodevelopmental Toxicology

The overall goal of Project 3 has been to determine if exposure to environmental toxicants early in development contributes to the etiology of autism and related neurodevelopmental disorders. Two related goals are to determine whether syndromic forms of autism (e.g., MECP2 mutations or FMR1 mutations) susceptibility to environmental contaminants (PCB and PBDEs) increases the severity for neurodevelopmental outcomes, and if maternal autoantibodies found in women at risk for birthing an autistic child promote social impairments in a perinatal mouse model we have developed.

Specific Aim 1.1: To obtain a comprehensive behavioral profile, including information on social recognition, social communication and social interaction of C57BL/6J and SJL/J mice following perinatal (pre- and postnatal) exposure to MeHg, PCB 95 or BDE 47. Spatial memory and learning, sensory and motor performance, sensory gating, and fear/anxiety will also be examined and compared between mouse strains.

Specific Aim 1.2: To examine the brains of C57BL/6J and SJL/J mice for abnormal development at 10 weeks of age following perinatal exposure to MeHg, PCB 95 or BDE 47. Stereological procedures will be used to quantify neuronal numbers and possible loss in hippocampus, cerebellum and cortex. Western blotting and immunohistochemistry will be used to localize and quantify proteins linked to cell signaling pathways known to be altered by exposure to MeHg, PCB 95 or BDE 47 and thought to be associated with autism.

Specific Aim 2.1: To perform serologic studies to measure total immunoglobulins (IgG, IgM, IgA), cytokines (leptin, TNF-alpha, IL1, IL-19, IL-6, IL-4, IL-5, GMCSF), chemokines (RANTES, MCP-1, MIP-1 alpha, MIP-1 beta, IL-8), and look for the presence of autoantibodies to normal mouse brain in the plasma from exposed mice at 10 weeks of age. Perform cellular phenotypic analysis on splenocytes following mitogen activation.

Specific Aim 2.2: To measure the immune response to antigenic challenge. Immunize mice with a tetanus vaccine at 4 weeks, boosted at 6 weeks and sacrificed at 10 weeks for immune system assays. Measure antibody titers to tetanus by ELISA, as well as T-cell proliferation in response to challenge with tetanus toxoid, PHA and media. Measure cytokines FGF basic, GM-CSF, IFN-gamma, IL-1α, IL-1β, IL-4, IL-6, IL-10, ILκ-12p40/p70, IL-13, IL-17, IL-10, KC, MCP1, MIG, MIP-1α, TNF-α, VEGF and RANTES.

Specific Aim 3.1: To measure susceptibility to flurothyl-induced seizures in 5-week-old C57BL/6J and SJL/J mice with and without exposure to MeHg, PCB 95 or BDE 47. Test these animals at 10 weeks for susceptibility to kindling of pentylenetetrazole (PTZ)-induced seizures.

Specific Aim 3.2: To determine how developmental exposure to MeHg, PCB 95 or BDE 47 influences hippocampal excitability and plasticity (e.g., long-term potentiation) using the in vitro slice preparation. Define how GABR deficiency influences hippocampal excitability.

Specific Aim 4.1: To characterize behavioral effects of prenatal AA-IgG exposure in the two mouse strains, with and without MeHg exposure.

Specific Aim 4.2: To examine C57BL/6J and SJL/J mice exposed prenatally to AA-IgG for abnormal brain development, with and without MeHg exposure.

Administrative Core

The overall objective of the Administrative Core was to oversee and coordinate the operations of the Center’s activities and foster interactions and synergism among the projects and cores within the Center and with the community. Additionally, the Administrative Core facilitated data and resource sharing and provided budgetary and grant oversight.

Community Outreach and Translation Core

The Community Outreach and Translation Core (COTC) had two distinct and interrelated objectives. The first objective was to coordinate and implement an efficient and highly effective clinical interface between CCEH investigators and study participants. The second objective of the COTC was to translate scientific findings from CCEH research into simplified text and presentations in both English and Spanish that are more easily understood by study participants, our community partners, clinicians, state officials and the general public.

Analytical Chemistry Core

Our objectives were to (1) establish the metabolic pathways responsible for variations in lipid composition between autistic children and their siblings and between normal and immunologically challenged animal models of autism; (2) use global metabolomic procedures to search for biomarkers of autism; (3) provide analytical data on pesticide and other xenobiotic levels in cell and in vivo model systems and in serum samples from the CHARGE, CHARGE-BACK, MARBLES and other successor studies; and (4) develop new analytical methods for xenobiotics of interest to scientists in the program project.

Molecular Genomics Core

Our objectives were to (1) establish if genomic profiles in the blood of children with autism are different from typically developing children and children with developmental delays without autism; and (2) determine if immune function in subgroups of children with autism as shown by abnormal cytokines, chemokines and autoantibodies will correlate with differences of gene expression in specific cell types. Abnormalities in NK cells are postulated to account for at least some of the abnormal immune functions

Specific Aim 1.1: To perform genomic (expression microarray) studies on blood from children with autism in the 4- to 9-year-old range, and compare to the blood genomic profiles we have obtained in children with autism in the 2- to 5-year-old age range.

Specific Aim 1.2: To compare gene expression as a function of blood metal levels in age groups in A, A-R, ASD, MR/DD and GP groups.

Specific Aim 1.3: To examine genomic profiles in pregnant mothers who have given birth to a previous child with autism, and determine if there is a specific genomic profile that correlates with whether the mother is carrying a child destined to develop autism.

Specific Aim 2.1: To describe the gene expression profiles in the blood using specific white blood cell subsets for children with autism without regression, autism with regression and ASD children compared to GP and MR/DD children.

Specific Aim 2.2: To examine gene expression following stimulation or activation of specific white blood cell subsets of A, A-R, ASD, MR/DD and GP children with low-level mercury, immune cell stimulation/activation with vaccine antigens and cell-specific mitogens, and xenobiotics.

Statistical Analysis Core

The main objective of the Statistics Core (SC) was to provide CCEH researchers with statistical support and collaboration for autism research ranging from animal models to children's clinical and population-based studies. SC faculty collaborated with investigators in the development of new projects, in providing data analysis support, and by advising on statistical analysis and experimental design. Finally, we developed targeted methodologies motivated by CCEH studies.

Specific Aim 1: To provide consultation in study design and planning, including study design and framing of aims and hypotheses, sample size and power calculation, and analytical planning.

Specific Aim 2: To assist with data analysis and presentation of results from each Project and Core.

Specific Aim 3: To advise and assist CCEH researchers with the linkage of databases across Projects and Cores and on analysis of the resulting complex data and research questions.

Specific Aim 4: To foster development of necessary new biostatistics methods specific to the field of autism research by supporting applications for funded research, linking CCEH investigators who have challenging problems with statistical researchers specializing in related areas and encouraging graduate students in statistics/biostatistics to consider dissertations in this area.

Summary/Accomplishments (Outputs/Outcomes):

Project 1 (R83329201C001): Environmental Epidemiology

Over the last 10 years, the UC Davis Center for Children’s Environmental Health (CCEH) has launched two epidemiologic studies. Results cover a wide range of exposures during pregnancy and their associations with autism spectrum disorder (ASD) and other types of neurodevelopmental delay, including workplace chemicals, nutritional factors and their interactions with genes, mercury, air pollution, polybrominated diphenyl ethers (PBDEs), maternal metabolic conditions, and untreated maternal fever.

From this research, several factors increased ASD risk: (1) low folic acid intake in the periconception period, particularly if the mother or child had genotypes for inefficient folate metabolism or transmethylation; these gene-by-environment (GxE) interactions appear to be the first identified examples of synergistic interactions in the autism literature; (2) residence in late pregnancy within 300 m of a freeway (this work was done in collaboration with the University of Southern California Children’s Center); (3) maternal obesity or any metabolic condition (obesity, gestational or type 2 diabetes, hypertension); and (4) fever during pregnancy that went untreated. Although this latter study did not observe a significant association with influenza, the combination of potential misclassification (potential confusing of influenza with the common cold) and the condition being relatively rare may have contributed to low power, if a modest effect size is expected. On the other hand, certain evidence suggests that previously published associations with viral exposures may have been mediated by the maternal immune response rather than the infection itself, which is consistent with the stronger result we found for fever. We also published extensively on a wide range of immune markers in both children and their mothers, demonstrating dysregulated immune function in affected children and maternal lack of tolerance for specific fetal brain proteins.

We measured blood Hg in CHARGE children and determined that those with ASD or DD had lower levels than typically developing (TD) children. This difference was explained by lower fish consumption of cases compared with TDs. In further work, Hg was quantified in strands from the first haircut that some mothers brought, by laser ablation/ICP/MS. We also analyzed Hg in newborn bloodspots and Hg-by-GSTM1 interaction; no link to ASD was observed for exposure alone or in combination with GSTM1 genotype.

In other work, we have analyzed plasma PBDEs on 100 CHARGE Study children and found levels higher than previously reported in any population, likely due to high flammability standards in California and the young age of the children (most congeners are higher in children than adults). We also showed that certain foods contributed substantially to body burdens, a novel finding at the time. Nevertheless, PBDE levels did not differ comparing ASD to TD children. That this finding does not preclude a role of PBDEs in risk for ASD can be inferred from the impact of dietary sources: food consumption habits change dramatically in the early years of life, introducing errors when measuring in plasma collected post-diagnosis.

With regard to pesticides, we observed a robust association between the use of pyrethroid-containing products and risk for ASD. Frequent use (6 or more months during the pregnancy) conferred ORs of 3 or higher. An interaction also was found with a tandem repeat in the promoter region of the MAOA gene. Products containing only the less-toxic pyrethrins showed no association, and because families are unlikely to distinguish the two types, the associations are probably not due to recall bias. In other analyses, using the California PUR (Pesticide Use Report) database of agricultural and other commercial applications, our preliminary results implicate organophosphates, carbamates and pyrethroids in ASD or other neurodevelopmental deficits.

Further work from CHARGE has addressed mitochondrial dysfunction; sleep patterns; developmental trajectories, including regression; ethnic differences/similarities; pesticides; candidate neurotransmitter genes and FMR1; and minor physical anomalies, as well as epigenetics and gene expression. In addition to these publications, work is in review on GI symptoms, SSRIs and CNVs. 

Project 2 (R83329201C002): Immunological Susceptibility of Autism

Using samples collected as part of the CHARGE Study, we have shown a significant number of abnormalities in immune function that likely stem from increased immune activation and/or the loss of regulation of the immune system in autism spectrum disorder (ASD). Our initial studies in ASD children demonstrate increases in immune cell cytokine production and release, altered immunoglobulin levels, the presence of antibodies directed to brain proteins, increased natural killer cell gene expression and cellular function, altered T cell activation, enhanced monocyte function and increased pro-inflammatory plasma cytokines and chemokines levels when compared to age-, gender- and geographically matched typically developing (TD) children and children with developmental delays (DD) other than ASD. In parallel, we have shown decreased production of regulatory cytokines such as TGFβ1 in ASD compared to controls, suggesting there is a shift towards an inflammatory profile in ASD. Of importance, we found that many of the immunological parameters that are different in ASD are associated with increased impairments in behaviors characteristic of core features of ASD, in particular, deficits in social interactions and communication as assessed using quantitative scores derived from the ADOS and ADI-R, as well as aberrant behaviors assessed using the Aberrant Behavior Checklist (ABC). Taken together, these studies point towards immune dysfunction in many ASD individuals. Although the exact nature of immune dysfunction in ASD is not yet clear, these data strongly suggest that there is a lack of regulation of immune cells leading to dysregulated activation.

During the first Center funding period, we identified altered levels of the plasma immunoglobulins IgG and IgM. We found that children with AU between the ages of 2 to 5 years have a significantly reduced level of plasma IgG compared to the TD (P<0.001) and DD children (P<0.001). Ig levels were negatively correlated with ABC scores for all children (IgG: r = -0.334, p < 0.0001; IgM: r = -0.167, p = 0.0285), where those patients with the highest scores in the behavioral battery have the most reduced levels of IgG and IgM. This study suggested a possible defect in B cell function. Therefore, during the second CCEH funding cycle, we brought these same children back to the clinic to perform extensive studies on their isolated B cells (those cells responsible for antibody production). Our results demonstrated no differences in the B cell parameters measured, indicating that decreased IgG in autism is not a result of B cell dysfunction and that other immune cells might be involved.

Furthermore, we recently showed that ASD children have increased susceptibility to exposure to environmentally relevant levels of a common environmental contaminant 2,2’,4,4’-tetrabrominated biphenyl (BDE-47) that resulted in more pronounced innate immune dysfunction. Following a 4-hour exposure to 100 nM or 500 nM BDE-47, peripheral blood mononuclear cells (PBMC) were challenged with bacterial lipopolysaccharide (LPS), an innate immune activator, for an additional 48 hrs and cytokine production was measured using the LuminexTM multiplex platform. The cytokine responses of LPS-stimulated PBMC from ASD and typically developing subjects diverged in the presence of 100 nM BDE, where the ASD children but not controls demonstrated significantly increased IL-1β responses (P=0.033), an inflammatory cytokine produced predominantly by monocytes. These data suggest that in vitro exposure of PBMC to BDE-47 affects cell cytokine production in a pediatric population, with ASD children particularly sensitive to further activation after exposure to BDE-47. Taken together, these data would suggest that already activated innate immune responses in some children with ASD may become further activated or may be sensitive to further stimulation in the presence of environmental exposures. Using gene expression profiling, we also found that many immune-based genes were abnormally expressed in children with ASD and that this expression correlated to environmental exposures such as mercury or lead, suggesting that children with ASD have increased sensitivity to environmental exposures, leading to potential alterations in the immune response.

During the first CCEH funding period, we discovered maternal plasma antibodies against human fetal brain proteins at approximately 73 kDa and 37 kDa specific to mothers of ASD children, but not found in either control group (p = 0.0061). In an expanded study, we examined a larger cohort of mothers of children with autism and controls, yielding significant associations between the presence of IgG reactivity to fetal brain proteins at 37 and 73 kDa and a childhood diagnosis of full autism (p = 0.0005), which also correlated with lower expressive language scores (p = 0.005). Additionally, we found reactivity to proteins at 39 and 73 kDa, which correlated with the broader diagnosis of ASD (p = 0.0007) and increased irritability on the Aberrant Behavioral Checklist (p = 0.05). We now have identified the proteins highly expressed in fetal brain during development that are recognized by these maternal antibodies. In addition, we have recently published a study describing the potential role of the MET "C" allele polymorphism with respect to genetic susceptibility towards the production of maternal autoantibodies. Two patents have been issued for this discovery.

During the first CCEH funding period, we also determined pathological significance associated with these maternal autoantibodies following the transfer of IgG antibodies purified from mothers of both children with autism and controls during gestation into pregnant rhesus monkeys. Offspring whose mothers received IgG from control mothers were indistinguishable from untreated controls. During the second CCEH funding period, we performed a similar passive transfer study using a murine model. Following a single IV exposure to purified IgG from three mothers of children with ASD and three mothers of typically developing control children, we noted alterations in early growth trajectories, significantly impaired motor and sensory development, decreased sociability in males, as well as increased anxiety. This report demonstrated for the first time the effects of a single, low-dose gestational exposure of IgG derived from individual maternal antibodies on their offspring's physical and social development.

In addition to studies on maternal autoantibodies, we found in plasma samples collected from CHARGE (funding period 1) the specific antibody reactivity in ASD children compared to typically developing children (p = 0.003). Further studies demonstrated antibodies specific to GABAergic interneurons in plasma from children with ASD. Finally, we recently demonstrated by Western blot analysis of rhesus macaque adult cerebellum probed with plasma from children from the CHARGE study that autoantibodies specific for a 45 kDa cerebellar protein (corresponding to the 52 kDa human cerebellar protein) in children were associated with a diagnosis of autism (p = 0.017), while autoantibodies directed towards a 62 kDa protein were associated with the broader diagnosis of autism spectrum disorder (p = 0.043). Further, reactivity to both the 45 and 62 kDa bands was noted only in children with ASD (p = 0.001). Children with these autoantibodies had lower adaptive (p = 0.0008) and cognitive function (p = 0.005), as well as increased aberrant behaviors (p < 0.05) compared to children without these antibodies. Collectively, these data suggest that antibodies toward brain proteins in children are associated with lower adaptive and cognitive function, as well as core behaviors associated with autism.

Project 3 (R83329201C003): Neurodevelopmental Toxicology

During this project period, we completed and published two studies using wild-type and MECP2 knock out mice in the C57BL/6J background and one paper on PCB/PBDE levels in postmortem human brain samples. First, we documented accumulation of BDE-47 in several organ systems following perinatal exposure of WT mice to low levels of BDE-47 and provided evidence that such exposure is associated with early behavioral deficits in exposed neonates. Mice were exposed perinatally to 0.03, 0.1 or 1 mg/kg/day of BDE-47, a dose range chosen to encompass human exposure levels. Tissue levels of BDE-47 were measured in the blood, brain, fat and milk of dams and in whole fetal homogenate and blood and brain of pups on gestational day (GD) 15 and postnatal days (PNDs) 1, 10 and 21. From GD 15 to PND 1, levels of BDE-47 increased within dam tissues and then decreased from PNDs 1 to 21. Over the period of lactation, levels in dam milk were comparatively high when compared to both brain and blood for all dose groups. Measurable levels of BDE-47 were found in the fetus on GD 15, confirming gestational exposure. From PNDs 1 to 21, levels of BDE-47 in pup tissue increased over the period of lactation due to the transfer of BDE-47 through milk. Behavioral tests of fine motor function and learning and memory were carried out between postnatal weeks 5 and 17 in order to evaluate the neurobehavioral toxicity of BDE-47. Behavioral deficits were seen only in the Barnes spatial maze, where mice in the three exposure groups had longer latencies and traveled longer distances to find the escape hole when compared to vehicle control mice. These results support the conclusions that perinatal exposure to BDE-47 can have neurodevelopmental consequences and that lactational exposure represents a significant exposure risk during development.

In the second mouse study, we investigated whether epigenetic mechanisms such as DNA methylation are responsive to environmental influences and have long-lasting consequences. Because autism spectrum disorders have complex neurodevelopmental origins whereby both genetic and environmental factors are implicated, we tested whether mice with a Rett syndrome mutation in methyl-CpG binding protein 2 (Mecp2(308)) have heightened sensitivity to long-lasting effects of PBDE exposure. Mecp2(308/+) dams were perinatally exposed daily to 2,2',4,4'-tetrabromodiphenyl ether 47 (BDE-47) and bred to wild-type C57BL/6J males, and the offspring of each sex and genotype were examined for developmental, behavioral and epigenetic outcomes. Perinatal BDE-47 exposure negatively impacted fertility of Mecp2(308/+) dams and preweaning weights of females. Global hypomethylation of adult brain DNA was observed, specifically in female offspring perinatally exposed to BDE-47, and it coincided with reduced sociability in a genotype-independent manner. A reversing interaction of Mecp2 genotype on BDE-47 exposure was observed in a short-term memory test of social novelty that corresponded to increased Dnmt3a levels, specifically in BDE-47-exposed Mecp2(308/+) offspring. In contrast, learning and long-term memory in the Morris water maze was impaired by BDE-47 exposure in female Mecp2(308/+) offspring. These results demonstrate that a genetic and environmental interaction relevant to social and cognitive behaviors shows sexual dimorphism, epigenetic dysregulation, compensatory molecular mechanisms and specific behavioral deficits.

The relationship between PBDE/PCB levels and DNA methylation patterns in the brains of individuals with and without neurodevelopmental disorders has not been previously investigated. We analyzed 107 human frozen postmortem brain samples for eight PCBs and seven PBDEs by GC-micro electron capture detector and GC/MS using negative chemical ionization. Human brain samples were grouped as neurotypical controls (n = 43), neurodevelopmental disorders with known genetic basis (n = 32, including Down, Rett, Prader-Willi, Angelman, and 15q11-q13 duplication syndromes), and autism of unknown etiology (n = 32). Unexpectedly, PCB 95 was significantly higher in the genetic neurodevelopmental group, but not idiopathic autism, as compared to neurotypical controls. Interestingly, samples with detectable PCB 95 levels were almost exclusively those with maternal 15q11-q13 duplication (Dup15q) or deletion in Prader-Willi syndrome. When sorted by birth year, Dup15q samples represented five out of six of genetic neurodevelopmental samples born after the 1976 PCB ban exhibiting detectable PCB 95 levels. Dup15q was the strongest predictor of PCB 95 exposure over age, gender or year of birth. Dup15q brain showed lower levels of repetitive DNA methylation measured by LINE-1 pyrosequencing, but methylation levels were confounded by year of birth. These results demonstrate a novel paradigm by which specific POPs may predispose to genetic copy number variation of 15q11-q13. The results from these studies indicate the potential significance of PCB 95 exposures to human developmental health.

In this regard, we also completed two detailed mechanistic studies of how PCB 95 alters activity-dependent dendritic growth by altering the functions of ryanodine receptors and its downstream Ca2+-dependent signaling pathways. In the first, we demonstrate that environmentally relevant levels of NDL PCBs modulate neuronal connectivity via RyR-dependent effects on dendritic arborization. In addition, these findings identify RyR channel dysregulation as a novel mechanism contributing to dysmorphic dendritogenesis associated with heritable and environmentally triggered neurodevelopmental disorders.

In the second study, we tested the hypothesis that the CaMKI-CREB-Wnt2 signaling pathway couples NDL PCB-enhanced RyR activity to dendritic arborization. RyRs regulate the spatiotemporal dynamics of intracellular Ca2+ signals, but whether RyRs promote dendritic growth via the modulation of this signaling pathway is not known. Ca2+ imaging of dissociated cultures of primary rat hippocampal neurons indicated that PCB-95 (2,2',3,5'6-pentachlorobiphenyl; a potent RyR potentiator) enhanced synchronized Ca2+ oscillations in somata and dendrites that were blocked by ryanodine. As determined by Western blotting and quantitative polymerase chain reaction, PCB-95 also activated CREB and up-regulated Wnt2. Blocking CaMKK, CaMKIα/γ, MEK/ERK, CREB or Wnt2 prevented PCB-95-induced dendritic growth. Antagonism of γ-aminobutyric acid (GABA) receptors with bicuculline (BIC) phenocopied the dendrite-promoting effects of PCB-95, and pharmacological antagonism or siRNA knockdown of RyR blocked BIC-induced dendritic growth in dissociated and slice cultures of hippocampal neurons. We therefore concluded that RyR activity contributes to dynamic remodeling of dendritic architecture in response to NDL PCBs via CaMKI-CREB-Wnt2 signaling in rats. Our findings identify PCBs as candidate environmental risk factors for neurodevelopmental disorders, especially in children with heritable deficits in calcium signaling associated with autism.

Pesticides: We published a seminal paper identifying the molecular mechanisms by which the pesticide, triclosan, which is broadly used as an antibacterial, impairs EC coupling in skeletal and cardiac muscle and impairs contractility in vivo. The origin of this work follows our discovery of the biological activity of hydroxylated PBDEs that we previously reported in our last progress statement. In addition, we published an extensive review of the literature regarding pesticides and autism risk.

Mouse model of maternal autoantibody transfer: We completed a detailed investigation of a murine passive transfer model system to ascertain the effects of gestational exposure to a single intravenous dose of purified, brain-reactive IgG antibodies from individual mothers of children with autism (MAU) or mothers with typically developing children (MTD). Growth and behavioral outcomes in offspring were measured from postnatal days 8 to 65 in each group. Comparisons revealed alterations in early growth trajectories, significantly impaired motor and sensory development, and increased anxiety. This report demonstrates for the first time the effects of a single, low-dose gestational exposure of IgG derived from individual MAU on their offspring's physical and social development.

FMR1 models of autism: We published several papers that develop both a mouse and human model of ASD. In the mouse FMR1 premutation model, we have shown that defects in neuronal morphology and migration in a preCGG mouse model are associated with functional abnormalities. Mouse preCGG hippocampal neurons (170 CGG repeats) grown in vitro develop abnormal networks of clustered burst (CB) firing, as assessed by multielectrode array recordings and clustered patterns of spontaneous Ca2+ oscillations, neither typical of wild-type (WT) neurons. PreCGG neurons have reduced expression of vesicular GABA and glutamate (Glu) transporters (VGAT and VGLUT1, respectively), and preCGG hippocampal astrocytes display a rightward shift on Glu uptake kinetics compared with WT. These alterations in preCGG astrocytes and neurons are associated with 4- to 8-fold elevated Fmr1 mRNA and occur despite consistent expression of fragile X mental retardation protein levels at ∼50% of WT levels. Abnormal patterns of activity observed in preCGG neurons are pharmacologically mimicked in WT neurons by addition of Glu or the mGluR1/5 agonist, dihydroxyphenylglycine, to the medium, or by inhibition of astrocytic Glu uptake with dl-threo-β-benzyloxyaspartic acid, but not by the ionotropic Glu receptor agonists, α-2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid or N-methyl-d-aspartic acid. The mGluR1 (7-(hydroxyimino)cyclopropa [b]chromen-1a-carboxylate ethyl ester) or mGluR5 (2-methyl-6-(phenylethynyl)pyridine hydrochloride) antagonists reversed CB firing. Importantly, the acute addition of the neurosteroid allopregnanolone mitigated functional impairments observed in preCGG neurons in a reversible manner. These results demonstrate abnormal mGluR1/5 signaling in preCGG neurons, which is ameliorated by mGluR1/5 antagonists or augmentation of GABA(A) receptor signaling, and identify allopregnanolone as a candidate therapeutic lead but also implicating mechanisms that could implicate gene x environment interactions. We also published evidence of early mitochondrial impairments in this mouse model.

We have developed a human iPSC-derived neuronal cell model from human premutation patients. To investigate the underlying cellular neuropathology, we produced induced pluripotent stem cell-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 show that neurons harboring the stably-active, expanded allele (EX-Xa) have reduced postsynaptic density protein 95 protein expression, reduced synaptic puncta density and reduced neurite length. Importantly, such neurons are also 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 EX-Xa neurons after glutamate application. By excluding the individual genetic background variation, we have demonstrated neuronal phenotypes directly linked to the FMR1 premutation. Our approach represents a unique isogenic, X-chromosomal epigenetic model to aid the development of targeted therapeutics for FXTAS, and more broadly as a model for the study of common neurodevelopmental (e.g., autism) and neurodegenerative (e.g., Parkinsonism, dementias) disorders.

Genetics of Autism: Expansion of a CGG trinucleotide repeat (>200 repeats) in the 5'UTR of the fragile X mental retardation gene, is the single most prevalent cause of cognitive disabilities. Several screening studies for FXS, among individuals with ID from different ethnic populations, have indicated that the prevalence of the syndrome varies between 0.5 and 16%. Because of the high co-morbidity with autism, we have conducted a screening study of the cohort from CHARGE, a large-scale, population-based, case control study. We have identified six subjects carrying an expanded allele, which emphasizes the importance of screening for FXS in a population with intellectual disabilities and ASD.


Journal Articles: 274 Displayed | Download in RIS Format

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Journal Article Ahn KC, Zhao B, Chen J, Cherednichenko G, Sanmarti E, Denison MS, Lasley B, Pessah IN, Kultz D, Chang DPY, Gee SJ, Hammock BD. In vitro biologic activities of the antimicrobials triclocarban, its analogs, and triclosan in bioassay screens: receptor-based bioassay screens. Environmental Health Perspectives 2008;116(9):1203-1210. R833292 (2009)
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  • Journal Article Ahn KC, Gee SJ, Tsai H-J, Bennett D, Nishioka MG, Blum A, Fishman E, Hammock BD. Immunoassay for monitoring environmental and human exposure to the polybrominated diphenyl ether BDE-47. Environmental Science & Technology 2009;43(20):7784-7790. R833292 (Final)
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  • Journal Article Ahn KC, Kim H-J, McCoy MR, Gee SJ, Hammock BD. Immunoassays and biosensors for monitoring environmental and human exposure to pyrethroid insecticides. Journal of Agricultural and Food Chemistry 2011;59(7):2792-2802. R833292 (Final)
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  • Journal Article Ahn KC, Gee SJ, Kim H-J, Aronov PA, Vega H, Krieger RI, Hammock BD. Immunochemical analysis of 3-phenoxybenzoic acid, a biomarker of forestry worker exposure to pyrethroid insecticides. Analytical and Bioanalytical Chemistry 2011;401(4):1285-1293. R833292 (Final)
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  • Journal Article Ahn KC, Kasagami T, Tsai H-J, Schebb NH, Gee SJ, Hammock BD. An immunoassay to evaluate human/environmental exposure to the antimicrobial triclocarban. Environmental Science & Technology 2012;46(1):374-381. R833292 (Final)
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  • Journal Article Anderson PJ, Lango J, Carkeet C, Britten A, Krautler B, Hammock BD, Roth JR. One pathway can incorporate either adenine or dimethylbenzimidazole as an α-axial ligand of B12 cofactors in Salmonella enterica. Journal of Bacteriology 2008;190(4):1160-1171. R833292 (Final)
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  • Journal Article Angkustsiri K, Krakowiak P, Moghaddam B, Wardinsky T, Gardner J, Kalamkarian N, Hertz-Picciotto I, Hansen RL. Minor physical anomalies in children with autism spectrum disorders. Autism 2011;15(6):746-760. R833292 (2011)
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  • Journal Article Aronov PA, Hall LM , Dettmer K, Stephensen CB, Hammock BD. Metabolic profiling of major vitamin D metabolites using Diels-Alder derivatization and ultra-performance liquid chromatography-tandem mass spectrometry. Analytical and Bioanalytical Chemistry 2008;391(5):1917-1930. R833292 (Final)
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  • Journal Article Ashwood P, Kwong C, Hansen R, Hertz-Picciotto I, Croen L, Krakowiak P, Walker W, Pessah IN, Van de Water J. Brief report: plasma leptin levels are elevated in autism: association with early onset phenotype? Journal of Autism and Developmental Disorders 2008;38(1):169-175. R833292 (2007)
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  • Journal Article Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen RL, Croen LA, Ozonoff S, Pessah IN, Van de Water J. Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. Journal of Neuroimmunology 2008;204(1-2):149-153. R833292 (2009)
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  • Journal Article Ashwood P, Schauer J, Pessah IN, Van de Water JV. Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders. Journal of Neuroimmunology 2009;208(1-2):130-135. R833292 (2009)
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  • Journal Article Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain, Behavior, and Immunity 2011;25(1):40-45. R833292 (2010)
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  • Journal Article Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J. Altered T cell responses in children with autism. Brain, Behavior, and Immunity 2011;25(5):840-849. R833292 (2010)
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  • Journal Article Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J. Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. Journal of Neuroimmunology 2011;232(1-2):196-199. R833292 (2011)
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  • Journal Article Bannister RA, Pessah IN, Beam KG. The skeletal L-type Ca2+ current is a major contributor to excitation-coupled Ca2+ entry. Journal of General Physiology 2009;133(1):79-91. R833292 (2009)
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  • Journal Article Barile D, Marotta M, Chu C, Mehra R, Grimm R, Lebrilla CB, German JB. Neutral and acidic oligosaccharides in Holstein-Friesian colostrum during the first 3 days of lactation measured by high performance liquid chromatography on a microfluidic chip and time-of-flight mass spectrometry. Journal of Dairy Science 2010;93(9):3940-3949. R833292 (Final)
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  • Journal Article Baron CA, Tepper CG, Liu SY, Davis RR, Wang NJ, Schanen NC, Gregg JP.
 Genomic and functional profiling of duplicated chromosome 15 cell lines reveal regulatory alterations in UBE3A-associated ubiquitin-proteasome pathway processes. Human Molecular Genetics 2006;15(6):853-869. R833292 (Final)
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  • Journal Article Baron CA, Liu SY, Hicks C, Gregg JP. Utilization of lymphoblastoid cell lines as a system for the molecular modeling of autism. Journal of Autism and Developmental Disorders 2006;36(8):973-982. R833292 (Final)
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  • Journal Article Barrientos G, Bose DD, Feng W, Padilla I, Pessah IN. The Na+/Ca2+ exchange inhibitor 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate (KB-R7943) also blocks ryanodine receptors type 1 (RyR1) and type 2 (RyR2) channels. Molecular Pharmacology 2009;76(3):560-568. R833292 (2009)
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  • Journal Article Bauman MD, Lavenex P, Mason WA, Capitanio JP, Amaral DG. The development of social behavior following neonatal amygdala lesions in rhesus monkeys. Journal of Cognitive Neuroscience 2004;16(8):1388-1411. R833292 (Final)
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  • Journal Article Bennett DH, Wu XM, Teague CH, Lee K, Cassady DL, Ritz B, Hertz-Picciotto I. Passive sampling methods to determine household and personal care product use. Journal of Exposure Science & Environmental Epidemiology 2012;22(2):148-160. R833292 (2012)
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  • Journal Article Berman RF, Pessah IN, Mouton PR, Mav D, Harry J. Low-level neonatal thimerosal exposure: further evaluation of altered neurotoxic potential in SJL mice. Toxicological Sciences 2008;101(2):294-309. R833292 (2008)
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  • Journal Article Berman RF, Pessah IN, Mouton PR, Mav D, Harry GJ. Modeling neonatal thimerosal exposure in mice. Toxicological Sciences 2008;103(2):416. R833292 (2008)
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  • Journal Article Braunschweig D, Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen LA, Pessah IN, Van de Water J. Autism: maternally derived antibodies specific for fetal brain proteins. NeuroToxicology 2008;29(2):226-231. R833292 (2007)
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  • Journal Article Braunschweig D, Duncanson P, Boyce R, Hansen R, Ashwood P, Pessah IN, Hertz-Picciotto I, Van de Water J. Behavioral correlates of maternal antibody status among children with autism. Journal of Autism and Developmental Disorders 2012;42(7):1435-1445. R833292 (2011)
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  • Journal Article Bu B, Ashwood P, Harvey D, King IB, Water JV, Jin LW.
 Fatty acid compositions of red blood cell phospholipids in children with autism.
 Prostaglandins, Leukotrienes and Essential Fatty Acids 2006;74(4):215-221. R833292 (2007)
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  • Journal Article Buchen L. Scientists and autism: when geeks meet. Nature 2011;479(7371):25-27. R833292 (2012)
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  • Journal Article Buck Louis GM, Gray LE Jr, Marcus M, Ojeda SR, Pescovitz OH, Witchel SF, Sippell W, Abbott DH, Soto A, Tyl RW, Bourguignon JP, Skakkebaek NE, Swan SH, Golub MS, Wabitsch M, Toppari J, Euling SY. Environmental factors and puberty timing: expert panel research needs. Pediatrics 2008;121(Suppl 3):S192-S207. R833292 (2009)
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  • Journal Article Buie T, Campbell DB, Fuchs III GJ, Furuta GT, Levy J, Van de Water J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics 2010;125(Suppl 1):S1-S18. R833292 (Final)
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  • Journal Article Burke K, Cheng Y, Li B, Petrov A, Joshi P, Berman RF, Reuhl KR, DiCicco-Bloom E. Methylmercury elicits rapid inhibition of cell proliferation in the developing brain and decreases cell cycle regulator, cyclin E. NeuroToxicology 2006;27(6):970-981. R833292 (2009)
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  • Journal Article Cabanlit M, Maitland D, Wilson T, Simon S, Wun T, Gershwin ME, Van de Water J. Polyurethane shape-memory polymers demonstrate functional biocompatibility in vitro. Macromolecular Bioscience 2007;7(1):48-55. R833292 (2007)
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  • Journal Article Cabanlit M, Wills S, Goines P, Ashwood P, Van de Water J. Brain-specific utoantibodies in the plasma of subjects with autistic spectrum disorder. Annals of the New York Academy of Sciences 2007;1107:92-103. R833292 (2007)
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  • Journal Article California Dental Association Foundation, American College of Obstetricians and Gynecologists District IX. Oral health during pregnancy and early childhood: evidence-based guidelines for health professionals. Journal of the California Dental Association 2010;38(6):391-403, 405-440. R833292 (2010)
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  • Journal Article Campbell MA, Golub MS, Iyer P, Kaufman FL, Li LH, Moran Messen F, Morgan JE, Donald JM. Reduced water intake: implications for rodent developmental and reproductive toxicity studies. Birth Defects Research Part B: Developmental and Reproductive Toxicology 2009;86(3):157-175. R833292 (2009)
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  • Journal Article Cao Z, Hammock BD, McCoy M, Rogawski M, Lein PJ, Pessah IN. Tetramethylenedisulfotetramine alters Ca2+ dynamics in cultured hippocampal neurons: mitigation by NMDA receptor blockade and GABAA receptor-positive modulation. Toxicological Sciences 2012;130(2):362-372. R833292 (2012)
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  • Journal Article Careaga M, Van de Water J, Ashwood P. Immune dysfunction in autism: a pathway to treatment. Neurotherapeutics 2010;7(3):283-292. R833292 (2011)
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  • Journal Article Carkeet C, Dueker SR, Lango J, Buchholz BA, Miller JW, Green R, Hammock BD, Roth JR, Anderson PJ. Human vitamin B12 absorption measurement by accelerator mass spectrometry using specifically labeled 14C-cobalamin. Proceedings of the National Academy of Sciences of the United States of America 2006;103(15):5694-5699. R833292 (Final)
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  • Journal Article Chaidez V, Hansen RL, Hertz-Picciotto I. Autism spectrum disorders in Hispanics and non-Hispanics. Autism: The International Journal of Research and Practice 2012;16(4):381-397. R833292 (2012)
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  • Journal Article Chelu MG, Goonasekera SA, Durham WJ, Tang W, Lueck JD, Riehl J, Pessah IN, Zhang P, Bhattacharjee MB, Dirksen RT, Hamilton SL. Heat-and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse. FASEB Journal 2006;20(2):329-330. R833292 (2007)
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  • Journal Article Chen Y, Tassone F, Berman RF, Hagerman PJ, Hagerman RJ, Willemsen R, Pessah IN. Murine hippocampal neurons expressing Fmr1 gene premutations show early developmental deficits and late degeneration. Human Molecular Genetics 2010;19(1):196-208. R833292 (Final)
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  • Journal Article Cherednichenko G, Zhang R, Bannister RA, Timofeyev V, Li N, Fritsch EB, Feng W, Barrientos GC, Schebb NH, Hammock BD, Beam KG, Chiamvimonvat N, Pessah IN. Triclosan impairs excitation-contraction coupling and Ca2+ dynamics in striated muscle. Proceedings of the National Academy of Sciences of the United States of America 2012;109(35):14158-14163. R833292 (2012)
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  • Journal Article Chichlowski M, German JB, Lebrilla CB, Mills DA. The influence of milk oligosaccharides on microbiota of infants: opportunities for formulas. Annual Review of Food Science and Technology 2011;2:331-351. R833292 (2012)
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  • Journal Article Croen LA, Goines P, Braunschweig D, Yolken R, Yoshida CK, Grether JK, Fireman B, Kharrazi M, Hansen RL, Van de Water J. Brain-derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) Study. Autism Research 2008;1(2):130-137. R833292 (2008)
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  • Journal Article Croen LA, Braunschweig D, Haapanen L, Yoshida CK, Fireman B, Grether JK, Kharrazi M, Hansen RL, Ashwood P, Van de Water J. Maternal mid-pregnancy autoantibodies to fetal brain protein: the Early Markers for Autism Study. Biological Psychiatry 2008;64(7):583-588. R833292 (2008)
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  • Journal Article Crofton KM, Mundy WR, Lein PJ, Bal-Price A, Coecke S, Coecke S, Seiler AEM, Knaut H, Buzanska L, Goldberg A. Developmental neurotoxicity testing: recommendations for developing alternative methods for the screening and prioritization of chemicals. ALTEX 2011;28(1):9-15. R833292 (2012)
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  • Journal Article Dai JJ, Lieu L, Rocke D.
 Dimension reduction for classification with gene expression microarray data.
 Statistical Applications in Genetics and Molecular Biology 2006;5(1):Article 6 (19 pp.). R833292 (Final)
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  • Journal Article Dallas DC, Martin WF, Strum JS, Zivkovic AM, Smilowitz JT, Underwood MA, Affolter M, Lebrilla CB, German JB. N-linked glycan profiling of mature human milk by high-performance microfluidic chip liquid chromatography time-of-flight tandem mass spectrometry. Journal of Agricultural and Food Chemistry 2011;59(8):4255-4263. R833292 (2012)
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  • Journal Article Davis BB, Morisseau C, Newman JW, Pedersen TL, Hammock BD, Weiss RH. Attenuation of vascular smooth muscle cell proliferation by 1-cyclohexyl-3-dodecyl urea is independent of soluble epoxide hydrolase inhibition. Journal of Pharmacology and Experimental Therapeutics 2006;316(2):815-821. R833292 (Final)
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  • Journal Article Denning L, Anderson JA, Davis R, Gregg JP, Kuzdenyi J, Maselli RA.
 High throughput genetic analysis of congenital myasthenic syndromes using resequencing microarrays. PLoS One 2007;2(9):e918. R833292 (Final)
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  • Journal Article Dettmer K, Hanna D, Whetstone P, Hansen R, Hammock BD. 
Autism and urinary exogenous neuropeptides: development of an on-line SPE-HPLC-tandem mass spectrometry method to test the opioid excess theory.
 Analytical and Bioanalytical Chemistry 2007;388(8):1643-1651. R833292 (Final)
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  • Journal Article Dettmer K, Aronov PA, Hammock BD. 
Mass spectrometry-based metabolomics.
 Mass Spectrometry Reviews 2007;26(1):51-78. R833292 (Final)
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  • Journal Article Dodds ED, German JB, Lebrilla CB. Enabling MALDI-FTICR-MS/MS for high-performance proteomics through combination of infrared and collisional activation. Analytical Chemistry 2007;79(24):9547-9556. R833292 (Final)
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  • Journal Article Du XL, Tang Y, Xu H, Lit L, Walker W, Ashwood P, Gregg JP, Sharp FR. Genomic profiles for human peripheral blood T cells, B cells, natural killer cells, monocytes, and polymorphonuclear cells: comparisons to ischemic stroke, migraine, and Tourette syndrome. Genomics 2006;87(6):693-703. R833292 (Final)
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  • Journal Article Enstrom AM, Lit L, Onore CE, Gregg JP, Hansen RL, Pessah IN, Hertz-Picciotto I, Van de Water JA, Sharp FR, Ashwood P. Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain, Behavior, and Immunity 2009:23(1):124-133. R833292 (2009)
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  • Journal Article Enstrom AM, Van de Water JA, Ashwood P. Autoimmunity in autism. Current Opinion in Investigational Drugs 2009;10(5):463-473. R833292 (Final)
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  • Journal Article Enstrom AM, Onore CE, Van de Water JA, Ashwood P. Differential monocyte responses to TLR ligands in children with autism spectrum disorders. Brain, Behavior, and Immunity 2010;24(1):64-71. R833292 (2009)
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  • Journal Article Enstrom A, Onore C, Hertz-Picciotto I, Hansen R, Croen L, Van de Water J, Ashwood P. Detection of IL-17 and IL-23 in plasma samples of children with autism. American Journal of Biochemistry and Biotechnology 2008;4(2):114-120. R833292 (2007)
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  • Journal Article Enstrom A, Onore C, Tarver A, Hertz-Picciotto I, Hansen R, Croen L, Van de Water J, Ashwood P. Peripheral blood leukocyte production of BDNF following mitogen stimulation in early onset and regressive autism. American Journal of Biochemistry and Biotechnology 2008;4(2):121-129. R833292 (2007)
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  • Journal Article Enstrom A, Krakowiak P, Onore C, Pessah IN, Hertz-Picciotto I, Hansen RL, Van de Water JA, Ashwood P. Increased IgG4 levels in children with autism disorder. Brain, Behavior, and Immunity 2009;23(3):389-395. R833292 (2009)
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  • Journal Article Esteve E, Smida-Rezgui S, Sarkozi S, Szegedi C, Regaya I, Chen L, Altafaj X, Rochat H, Allen P, Pessah IN, Marty I, Sabatier JM, Jona I, De Waard M, Ronjat M. Critical amino acid residues determine the binding affinity and the Ca2+ release efficacy of maurocalcine in skeletal muscle cells. Journal of Biological Chemistry 2003;278(39):37822-37831. R833292 (Final)
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  • Journal Article Fang X, Hu S, Watanabe T, Weintraub NL, Snyder GD, Yao J, Liu Y, Shyy JY-J, Hammock BD, Spector AA. Activation of peroxisome proliferator-activated receptor α by substituted urea-derived soluble epoxide hydrolase inhibitors. Journal of Pharmacology and Experimental Therapeutics 2005;314(1):260-270. R833292 (Final)
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  • Journal Article Feng W, Tu J, Pouliquin P, Cabrales E, Shen X, Dulhunty A, Worley PF, Allen PD, Pessah IN. Dynamic regulation of ryanodine receptor type 1 (RyR1) channel activity by Homer 1. Cell Calcium 2008;43(3):307-314. R833292 (2007)
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  • Journal Article Feng W, Barrientos GC, Cherednichenko G, Yang T, Padilla IT, Truong K, Allen PD, Lopez JR, Pessah IN. Functional and biochemical properties of ryanodine receptor type 1 channels from heterozygous R163C malignant hyperthermia-susceptible mice. Molecular Pharmacology 2011;79(3):420-431. R833292 (2012)
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  • Journal Article Froehlich JW, Dodds ED, Barboza M, McJimpsey EL, Seipert RR, Francis J, An HJ, Freeman S, German JB, Lebrilla CB. Glycoprotein expression in human milk during lactation. Journal of Agricultural and Food Chemistry 2010;58(10):6440-6448. R833292 (Final)
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  • Journal Article German JB, Smilowitz JT, Zivkovic AM. Lipoproteins: when size really matters. Current Opinion in Colloid & Interface Science 2006;11(2-3):171-183. R833292 (Final)
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  • Journal Article German JB, Gillies LA, Smilowitz JT, Zivkovic AM, Watkins SM. Lipidomics and lipid profiling in metabolomics.
 Current Opinion in Lipidology 2007;18(1):66-71. R833292 (Final)
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  • Journal Article German JB. Dietary lipids from an evolutionary perspective: sources, structures and functions. Maternal & Child Nutrition 2011;7(Suppl 2):2-16. R833292 (2012)
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  • Journal Article German JB, Zivkovic AM, Dallas DC, Smilowitz JT. Nutrigenomics and personalized diets: what will they mean for food? Annual Review of Food Science and Technology 2011;2:97-123. R833292 (2012)
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  • Journal Article Gibney MJ, Walsh M, Brennan L, Roche HM, German B, van Ommen B. Metabolomics in human nutrition: opportunities and challenges. American Journal of Clinical Nutrition 2005;82(3):497-503. R833292 (Final)
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  • Journal Article Giulivi C, Zhang Y-F, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN. Mitochondrial dysfunction in autism. JAMA-Journal of the American Medical Association 2010;304(21):2389-2396. R833292 (2012)
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  • Journal Article Giulivi C, Ross-Inta C, Omanska-Klusek A, Napoli E, Sakaguchi D, Barrientos G, Allen PD, Pessah IN. Basal bioenergetic abnormalities in skeletal muscle from ryanodine receptor malignant hyperthermia-susceptible R163C knock-in mice. Journal of Biological Chemistry 2011;286(1):99-113. R833292 (2012)
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  • Journal Article Goines PE, Croen LA, Braunschweig D, Yoshida, CK, Grether J, Hansen R, Kharrazi M, Ashwood P, Van de Water J. Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: a case-control study. Molecular Autism 2011;2:13. R833292 (2011)
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  • Journal Article Goines P, Schauer J, Heuer L, Ashwood P, Van de Water J. Beta-2-microglobulin in autism spectrum disorders. American Journal of Biochemistry and Biotechnology 2007;3(2):87-91. R833292 (2007)
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  • Journal Article Goines P, Van de Water J. The immune system's role in the biology of autism. Current Opinion in Neurology 2010;23(2):111-117. R833292 (2009)
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  • Journal Article Goines P, Haapanen L, Boyce R, Duncanson P, Braunschweig D, Delwiche L, Hansen R, Hertz-Picciotto I, Ashwood P, Van de Water J. Autoantibodies to cerebellum in children with autism associate with behavior. Brain, Behavior, and Immunity 2011;25(3):514-523. R833292 (2011)
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  • Journal Article Goth SR, Chu RA, Pessah IN. Oxygen tension regulates the in vitro maturation of GM-CSF expanded murine bone marrow dendritic cells by modulating class II MHC expression. Journal of Immunological Methods 2006;308(1-2):179-191. R833292 (2007)
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  • Journal Article Goth SR, Chu RA, Gregg JP, Cherednichenko G, Pessah IN. Uncoupling of ATP-mediated calcium signaling and dysregulated interleukin-6 secretion in dendritic cells by nanomolar thimerosal. Environmental Health Perspectives 2006;114(7):1083-1091. R833292 (2007)
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  • Journal Article Greco CM, Navarro CS, Hunsaker MR, Maezawa I, Shuler JF, Tassone F, Delany M, Au JW, Berman RF, Jin L-W, Schumann C, Hagerman PJ, Hagerman RJ. Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome. Molecular Autism 2011;2(1):2 (13 pp.). R833292 (2012)
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  • Journal Article Gregg JP, Lit L, Baron CA, Hertz-Picciotto I, Walker W, Davis RA, Croen LA, Ozonoff S, Hansen R, Pessah IN, Sharp FR. Gene expression changes in children with autism. Genomics 2008;91(1):22-29. R833292 (2008)
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  • Journal Article Hall LM, Kimlin MG, Aronov PA, Hammock BD, Slusser JR, Woodhouse LR, Stephensen CB. Vitamin D intake needed to maintain target serum 25-hydroxyvitamin D concentrations in participants with low sun exposure and dark skin pigmentation is substantially higher than current recommendations. Journal of Nutrition 2010;140(3):542-550. R833292 (Final)
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  • Journal Article Halladay AK, Amaral D, Aschner M, Bolivar VJ, Bowman A, DiCicco-Bloom E, Hyman SL, Keller F, Lein P, Pessah I, Restifo L, Threadgill DW. Animal models of autism spectrum disorders: information for neurotoxicologists. NeuroToxicology 2009;30(5):811-821. R833292 (Final)
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  • Journal Article Hansen RL, Ozonoff S, Krakowiak P, Angkustsiri K, Jones C, Deprey LJ, Le D-N, Croen LA, Hertz-Picciotto I. Regression in autism: prevalence and associated factors in the CHARGE Study. Ambulatory Pediatrics 2008;8(1):25-31. R833292 (2008)
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  • Journal Article Herr CE, Dostal M, Ghosh R, Ashwood P, Lipsett M, Pinkerton KE, Sram R, Hertz-Picciotto I. Air pollution exposure during critical time periods in gestation and alterations in cord blood lymphocyte distribution: a cohort of livebirths. Environmental Health 2010;9:46. R833292 (2010)
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  • Journal Article Herr CEW, Ghosh R, Dostal M, Skokanova V, Ashwood P, Lipsett M, Joad JP, Pinkerton KE, Yap P-S, Frost JD, Sram R, Hertz-Picciotto I. Exposure to air pollution in critical prenatal time windows and IgE levels in newborns. Pediatric Allergy and Immunology 2011;22(1 Pt 1):75-84. R833292 (2011)
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  • Journal Article Hertz-Picciotto I, Charles MJ, James RA, Keller JA, Willman E, Teplin S. In utero polychlorinated biphenyl exposures in relation to fetal and early childhood growth. Epidemiology 2005;16(5):648-656. R833292 (2007)
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  • Journal Article Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN. The CHARGE Study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environmental Health Perspectives 2006;114(7):1119-1125. R833292 (2007)
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  • Journal Article Hertz-Picciotto I, Baker RJ, Yap PS, Dostal M, Joad JP, Lipsett M, Greenfield T, Herr CE, Benes I, Shumway RH, Pinkerton KE, Sram R. Early childhood lower respiratory illness and air pollution. Environmental Health Perspectives 2007;115(10):1510-1518. R833292 (2007)
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  • Journal Article Hertz-Picciotto I, Park HY, Dostal M, Kocan A, Trnovec T, Sram R. Prenatal exposures to persistent and non-persistent organic compounds and effects on immune system development. Basic and Clinical Pharmacology and Toxicology 2008;102(2):146-154. R833292 (2008)
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  • Journal Article Hertz-Picciotto I, Jusko TA, Willman EJ, Baker RJ, Keller JA, Teplin SW, Charles MJ. A cohort study of in utero polychlorinated biphenyl (PCB) exposures in relation to secondary sex ratio. Environmental Health 2008;7:37. R833292 (2009)
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  • Journal Article Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology 2009;20(1):84-90. R833292 (2009)
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  • Journal Article Hertz-Picciotto I, Cassady D, Lee K, Bennett DH, Ritz B, Vogt R. Study of Use of Products and Exposure-Related Behaviors (SUPERB):study design, methods, and demographic characteristics of cohorts. Environmental Health 2010;9:54 (14 pp.). R833292 (2010)
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  • Journal Article Hertz-Picciotto I, Green PG, Delwiche L, Hansen R, Walker C, Pessah IN. Blood mercury concentrations in CHARGE Study children with and without autism. Environmental Health Perspectives 2010;118(1):161-166. R833292 (2009)
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  • Journal Article Hertz-Picciotto I, Bergman A, Fangstrom B, Rose M, Krakowiak P, Pessah I, Hansen R, Bennett DH. Polybrominated diphenyl ethers in relation to autism and developmental delay: a case-control study. Environmental Health 2011;10(1):1. R833292 (2011)
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  • Journal Article Heuer LS, Rose M, Ashwood P, Van de Water J. Decreased levels of total immunoglobulin in children with autism are not a result of B cell dysfunction. Journal of Neuroimmunology 2012;251(1-2):94-102. R833292 (2012)
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  • Journal Article Heuer L, Ashwood P, Schauer J, Goines P, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen LA, Pessah IN, Van de Water J. Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms. Autism Research 2008;1(5):275-283. R833292 (2009)
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  • Journal Article Heuer L, Braunschweig D, Ashwood P, Van de Water J, Campbell DB. Association of a MET genetic variant with autism-associated maternal autoantibodies to fetal brain proteins and cytokine expression. Translational Psychiatry 2011;1:e48. R833292 (2011)
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  • Journal Article Hillyard SL, German JB. Non-essential dietary factors: from test tube to lifespan. Journal of the Science of Food and Agriculture 2007;87(10):1802-1805. R833292 (Final)
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  • Journal Article Hillyard SL, German JB. Quantitative lipid analysis and life span of the fat-3 mutant of Caenorhabditis elegans. Journal of Agricultural and Food Chemistry 2009;57(8):3389-3396. R833292 (Final)
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  • Journal Article Horvathova M, Jahnova E, Palkovicova L, Trnovec T, Hertz-Picciotto I. Dynamics of lymphocyte subsets in children living in an area polluted by polychlorinated biphenyls. Journal of Immunotoxicology 2011;8(4):333-345. R833292 (2012)
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  • Journal Article Horvathova M, Jahnova E, Palkovicova L, Trnovec T, Hertz-Picciotto I. The kinetics of cell surface receptor expression in children perinatally exposed to polychlorinated biphenyls. Journal of Immunotoxicology 2011;8(4):367-380. R833292 (2012)
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  • Journal Article Howards PP, Hertz-Picciotto I. Invited commentary: disinfection by-products and pregnancy loss—lessons. American Journal of Epidemiology 2006;164(11):1052-1055. R833292 (2007)
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  • Journal Article Hua S, Nwosu CC, Strum JS, Seipert RR, An HJ, Zivkovic AM, German JB, Lebrilla CB. Site-specific protein glycosylation analysis with glycan isomer differentiation. Analytical and Bioanalytical Chemistry 2012;403(5):1291-1302. R833292 (2012)
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  • Journal Article Huang H, Nishi K, Gee SJ, Hammock BD. Evaluation of chiral α-cyanoesters as general fluorescent substrates for screening enantioselective esterases. Journal of Agricultural and Food Chemistry 2006;54(3):694-699. R833292 (Final)
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  • Journal Article Hwang H-M, Park E-K, Young TM, Hammock BD. Occurrence of endocrine-disrupting chemicals in indoor dust. Science of the Total Environment 2008;404(1):26-35. R833292 (Final)
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  • Journal Article Inceoglu B, Schmelzer KR, Morisseau C, Jinks SL, Hammock BD.
 Soluble epoxide hydrolase inhibition reveals novel biological functions of epoxyeicosatrienoic acids (EETs). 
Prostaglandins & Other Lipid Mediators 2007;82(1-4):42-49. R833292 (Final)
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  • Journal Article Jaubert PJ, Golub MS, Lo YY, Germann SL, Dehoff MH, Worley PF, Kang SH, Schwarz MK, Seeburg PH, Berman RF. Complex, multimodal behavioral profile of the Homer1 knockout mouse. Genes, Brain and Behavior 2007;6(2):141-154. R833292 (2007)
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  • Journal Article Jusko TA, Koepsell TD, Baker RJ, Greenfield TA, Willman EJ, Charles MJ, Teplin SW, Checkoway H, Hertz-Picciotto I. Maternal DDT exposures in relation to fetal and 5-year growth. Epidemiology 2006;17(6):692-700. R833292 (2007)
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  • Journal Article Jusko TA, De Roos AJ, Schwartz SM, Lawrence BP, Palkovicova L, Nemessanyi T, Drobna B, Fabisikova A, Kocan A, Sonneborn D, Jahnova E, Kavanagh TJ, Trnovec T, Hertz-Picciotto I. A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age. Environmental Research 2010;110(4):388-395. R833292 (2010)
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  • Journal Article Kania-Korwel I, Barnhart CD, Stamou M, Truong KM, El-Komy MHME, Lein PJ, Veng-Pedersen P, Lehmler H-J. 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) and its hydroxylated metabolites are enantiomerically enriched in female mice. Environmental Science & Technology 2012;46(20):11393-11401. R833292 (2012)
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  • Journal Article Kenet T, Froemke RC, Schreiner CE, Pessah IN, Merzenich MM. Perinatal exposure to a noncoplanar polychlorinated biphenyl alters tonotopy, receptive fields, and plasticity in rat primary auditory cortex.
 Proceedings of the National Academy of Sciences of the United States of America 2007;104(18):7646-7651. R833292 (2007)
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  • Journal Article Kim H-J, Ahn KC, Ma SJ, Gee SJ, Hammock BD.
 Development of sensitive immunoassays for the detection of the glucuronide conjugate of 3-phenoxybenzyl alcohol, a putative human urinary biomarker for pyrethroid exposure. Journal of Agricultural and Food Chemistry 2007;55(10):3750-3757. R833292 (Final)
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  • Journal Article Kim H-J, McCoy M, Gee SJ, Gonzalez-Sapienza GG, Hammock BD. Noncompetitive phage anti-immunocomplex real-time polymerase chain reaction for sensitive detection of small molecules. Analytical Chemistry 2011;83(1):246-253. R833292 (2012)
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  • Journal Article Kim H-J, McCoy MR, Majkova Z, Dechant JE, Gee SJ, Tabares-da Rosa S, Gonzalez-Sapienza GG, Hammock BD. Isolation of alpaca anti-hapten heavy chain single domain antibodies for development of sensitive immunoassay. Analytical Chemistry 2012;84(2):1165-1171. R833292 (2012)
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  • Journal Article Kim H-J, Rossotti MA, Ahn KC, Gonzalez-Sapienza GG, Gee SJ, Musker R, Hammock BD. Development of a noncompetitive phage anti-immunocomplex assay for brominated diphenyl ether 47. Analytical Biochemistry 2010;401(1):38-46. R833292 (Final)
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  • Journal Article Kim KH, Inan SY, Berman RF, Pessah IN. Excitatory and inhibitory synaptic transmission is differentially influenced by two ortho-substituted polychlorinated biphenyls in the hippocampal slice preparation. Toxicology and Applied Pharmacology 2009;237(2):168-177. R833292 (Final)
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  • Journal Article Kim KH, Bose DD, Ghogha A, Riehl J, Zhang R, Barnhart CD, Lein PJ, Pessah IN. Para-and ortho-substitutions are key determinants of polybrominated diphenyl ether activity toward ryanodine receptors and neurotoxicity. Environmental Health Perspectives 2011;119(4):519-526. R833292 (2012)
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  • Journal Article Kim KH, Pessah IN. Perinatal exposure to environmental polychlorinated biphenyls sensitizes hippocampus to excitotoxicity ex vivo. NeuroToxicology 2011;32(6):981-985. R833292 (2011)
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  • Journal Article Koenig CM, Walker CK, Qi L, Pessah IN, Berman RF. Lack of evidence for neonatal misoprostol neurodevelopmental toxicity in C57BL6/J mice. PLoS ONE 2012;7(6):e38911 (7 pp.). R833292 (2012)
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  • Journal Article 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. R833292 (2012)
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  • Journal Article Krakowiak P, Goodlin-Jones B, Hertz-Picciotto I, Croen LA, Hansen RL.
Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: a population-based study. 
Journal of Sleep Research 2008;17(2):197-206. R833292 (2007)
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  • Journal Article Krakowiak P, Walker CK, Bremer AA, Baker AS, Ozonoff S, Hansen RL, Hertz-Picciotto I. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 2012;129(5):e1121-e1128. R833292 (2012)
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  • Journal Article Lange MC, Lemay DG, German JB. A multi-ontology framework to guide agriculture and food towards diet and health. Journal of the Science of Food and Agriculture 2007;87(8):1427-1434. R833292 (Final)
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  • Journal Article Lee H, Lerno Jr. LA, Choe Y, Chu CS, Gillies LA, Grimm R, Lebrilla CB, German JB. Multiple precursor ion scanning of gangliosides and sulfatides with a reversed-phase microfluidic chip and quadrupole time-of-flight mass spectrometry. Analytical Chemistry 2012;84(14):5905-5912. R833292 (2012)
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  • Journal Article Lein PJ, Barnhart CD, Pessah IN. Acute hippocampal slice preparation and hippocampal slice cultures. Methods in Molecular Biology 2011;758:115-134. R833292 (Final)
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  • Journal Article Lemay DG, Neville MC, Rudolph MC, Pollard KS, German JB.
 Gene regulatory networks in lactation: identification of global principles using bioinformatics. BMC Systems Biology 2007;1:56 (24 pp.). R833292 (Final)
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  • Journal Article Lemay DG, Zivkovic AM, German JB.
 Building the bridges to bioinformatics in nutrition research. American Journal of Clinical Nutrition 2007;86(5):1261-1269. R833292 (Final)
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  • Journal Article Lemay DG, Lynn DJ, Martin WF, Neville MC, Casey TM, Rincon G, Kriventseva EV, Barris WC, Hinrichs AS, Molenaar AJ, Pollard KS, Maqbool NJ, Singh K, Murney R, Zdobnov EM, Tellam RL, Medrano JF, German JB, Rijnkels M. The bovine lactation genome: insights into the evolution of mammalian milk. Genome Biology 2009;10(4):R43 (18 pp.). R833292 (Final)
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  • Journal Article Li L. Survival prediction of diffuse large-B-cell lymphoma based on both clinical and gene expression information. Bioinformatics 2006;22(4):466-471. R833292 (Final)
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  • Journal Article Li N, Liu J-Y, Timofeyev V, Qiu H, Hwang SH, Tuteja D, Lu L, Yang J, Mochida H, Low R, Hammock BD, Chiamvimonvat N. Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: insight gained using metabolomic approaches. Journal of Molecular and Cellular Cardiology 2009;47(6):835-845. R833292 (Final)
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  • Journal Article Li N, Liu J-Y, Qiu H, Harris TR, Sirish P, Hammock BD, Chiamvimonvat N. Use of metabolomic profiling in the study of arachidonic acid metabolism in cardiovascular disease. Congestive Heart Failure 2011;17(1):42-46. R833292 (Final)
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  • Journal Article Liu J, Koscielska KA, Cao Z, Hulsizer S, Grace N, Mitchell G, Nacey C, Githinji J, McGee J, Garcia-Arocena D, Hagerman RJ, Nolta J, Pessah IN, Hagerman PJ. Signaling defects in iPSC-derived fragile X premutation neurons. Human Molecular Genetics 2012;21(17):3795-3805. R833292 (2012)
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  • Journal Article Magby JP, Neal AP, Atchison WD, Pessah IP, Shafer TJ. Channelopathies: summary of the hot topic keynotes session. NeuroToxicology 2011;32(5):661-665. R833292 (2011)
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  • Journal Article Martin LA, Ashwood P, Braunschweig D, Cabanlit M, Van de Water J, Amaral DG. Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain, Behavior, and Immunity 2008;22(6):806-816. R833292 (2008)
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  • Journal Article Masuno MN, Pessah IN, Olmstead MM, Molinski TF. Simplified cyclic analogues of bastadin-5. Structure-activity relationships for modulation of the RyR1/FKBP12 Ca2+ channel complex. Journal of Medicinal Chemistry 2006;49(15):4497-4511. R833292 (2007)
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  • Journal Article McCanlies EC, Fekedulegn D, Mnatsakanova A, Burchfiel CM, Sanderson WT, Charles LE, Hertz-Picciotto I. Parental occupational exposures and autism spectrum disorder. Journal of Autism and Developmental Disorders 2012;42(11):2323-2334. R833292 (2012)
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  • Journal Article Merin N, Young GS, Ozonoff S, Rogers SJ. Visual fixation patterns during reciprocal social interaction distinguish a subgroup of 6-month-old infants at-risk for autism from comparison infants. Journal of Autism and Developmental Disorders 2007;37(1):108-121. R833292 (2007)
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  • Journal Article Mitchell MM, Woods R, Chi L-H, Schmidt RJ, Pessah IN, Kostyniak PJ, LaSalle JM. Levels of select PCB and PBDE congeners in human postmortem brain reveal possible environmental involvement in 15q11-q13 duplication autism spectrum disorder. Environmental and Molecular Mutagenesis 2012;53(8):589-598. R833292 (2012)
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  • Journal Article Morisseau C, Merzlikin O, Lin A, He G, Feng W, Padilla I, Denison MS, Pessah IN, Hammock BD. Toxicology in the fast lane: application of high-throughput bioassays to detect modulation of key enzymes and receptors. Environmental Health Perspectives 2009;117(12):1867-1872. R833292 (2009)
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  • Journal Article Nagarajan RP, Patzel KA, Martin M, Yasui DH, Swanberg SE, Hertz-Picciotto I, Hansen RL, Van de Water J, Pessah IN, Jiang R, Robinson WP, LaSalle JM. MECP2 promoter methylation and X chromosome inactivation in autism. Autism Research 2008;1(3):169-178. R833292 (2008)
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  • Journal Article Newman JW, Kaysen GA, Hammock BD, Shearer GC. Proteinuria increases oxylipid concentrations in VLDL and HDL, but not LDL particles in the rat. Journal of Lipid Research 2007;48(8):1792-1800. R833292 (Final)
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  • Journal Article Nguyen DV, Senturk D. Distortion diagnostics for covariate-adjusted regression: graphical techniques based on local linear modeling.
 Journal of Data Science 2007;5(4):471-490. R833292 (Final)
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  • Journal Article Nguyen DV, Senturk D, Carroll RJ. Covariate-adjusted linear mixed effects model with an application to longitudinal data. Journal of Nonparametric Statistics 20(6):459-481. R833292 (Final)
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  • Journal Article Ninonuevo MR, Park Y, Yin H, Zhang J, Ward RE, Clowers BH, German JB, Freeman SL, Killeen K, Grimm R, Lebrilla CB. A strategy for annotating the human milk glycome.
 Journal of Agricultural and Food Chemistry 2006;54(20):7471-7480. R833292 (Final)
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  • Journal Article Ninonuevo MR, Ward RE, LoCascio RG, German JB, Freeman SL, Barboza M, Mills DA, Lebrilla CB. 
Methods for the quantitation of human milk oligosaccharides in bacterial fermentation by mass spectometry.
 Analytical Biochemistry 2007;361(1):15-23. R833292 (Final)
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  • Journal Article Oberbauer AM, German JB, Murray JD. Growth hormone enhances arachidonic acid metabolites in a growth hormone transgenic mouse. Lipids 2011;46(6):495-504. R833292 (2012)
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  • Journal Article Onore CE, Nordahl CW, Young GS, Van de Water JA, Rogers SJ, P Ashwood P. Levels of soluble adhesion molecules PECAM-1 and P-selectin are decreased in children with autism spectrum disorder. Biological Psychiatry 2012;72(12):1020-1025. R833292 (2012)
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  • Journal Article Onore C, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen R, Van de Water J, Ashwood P. Decreased cellular IL-23 but not IL-17 production in children with autism spectrum disorders. Journal of Neuroimmunology 2009;216(1-2):126-129. R833292 (2009)
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  • Journal Article Onore C, Careaga M, Ashwood P. The role of immune dysfunction in the pathophysiology of autism. Brain, Behavior, and Immunity 2012;26(3):383-392. R833292 (2011)
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  • Journal Article Ostrovskaya O, Goyal R, Osman N, McAllister CE, Pessah IN, Hume JR, Wilson SM. 
Inhibition of ryanodine receptors by 4-(2-aminopropyl)-3,5-dichloro-N,N-dimethylaniline (FLA 365) in canine pulmonary arterial smooth muscle cells.
 Journal of Pharmacology and Experimental Therapeutics 2007;323(1):381-390. R833292 (2007)
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  • Journal Article Ozonoff S, Young GS, Goldring S, Greiss-Hess L, Herrera AM, Steele J, Macari S, Hepburn S, Rogers SJ. Gross motor development, movement abnormalities, and early identification of autism. Journal of Autism and Developmental Disorders 2008;38(4):644-656. R833292 (2007)
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  • Journal Article Ozonoff S, Heung K, Byrd R, Hansen R, Hertz-Picciotto I. The onset of autism: patterns of symptom emergence in the first years of life. Autism Research 2008;1(6):320-328. R833292 (2009)
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  • Journal Article Ozonoff S, Iosif A-M, Young GS, Hepburn S, Thompson M, Colombi C, Cook IC, Werner E, Goldring S, Baguio F, Rogers SJ. Onset patterns in autism: correspondence between home video and parent report. Journal of the American Academy of Child & Adolescent Psychiatry 2011;50(8):796-806.e1. R833292 (2012)
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  • Journal Article Ozonoff S. The first cut is the deepest: why do the reported effects of treatments decline over trials? Journal of Child Psychology and Psychiatry 2011;52(7):729-730 (editorial). R833292 (2012)
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  • Journal Article Palkovicova L, Ursinyova M, Masanova V, Yu Z, Hertz-Picciotto I. Maternal amalgam dental fillings as the source of mercury exposure in developing fetus and newborn. Journal of Exposure Science & Environmental Epidemiology 2008;18(3):326-331. R833292 (2007)
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  • Journal Article Park HY, Hertz-Picciotto I, Sovcikova E, Kocan A, Drobna B, Trnovec T. Neurodevelopmental toxicity of prenatal polychlorinated biphenyls (PCBs) by chemical structure and activity: a birth cohort study. Environmental Health 2010;9:51. R833292 (2010)
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  • Journal Article Park H-Y, Hertz-Picciotto I, Petrik J, Palkovicova L, Kocan A, Trnovec T.
 Prenatal PCB exposure and thymus size at birth in neonates in Eastern Slovakia.
 Environmental Health Perspectives 2008;116(1):104-109. R833292 (Final)
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  • Journal Article Park H-Y, Park J-S, Sovcikova E, Kocan A, Linderholm L, Bergman A, Trnovec T, Hertz-Picciotto I. Exposure to hydroxylated polychlorinated biphenyls (OH-PCBs) in the prenatal period and subsequent neurodevelopment in Eastern Slovakia. Environmental Health Perspectives 2009;117(10):1600-1606. R833292 (Final)
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  • Journal Article Paul R, Pessah IN, Gane L, Ono M, Hagerman PJ, Brunberg JA, Tassone F, Bourgeois JA, Adams PE, Nguyen DV, Hagerman R. Early onset of neurological symptoms in fragile X premutation carriers exposed to neurotoxins. Neurotoxicology 2010;31(4):399-402. R833292 (2009)
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  • Journal Article Pessah IN, Hansen LG, Albertson TE, Garner CE, Ta TA, Do Z, Kim KH, Wong PW. Structure-activity relationship for noncoplanar polychlorinated biphenyl congeners toward the ryanodine receptor-Ca2+ channel complex type 1 (RyR1). Chemical Research in Toxicology 2006;19(1):92-101. R833292 (2007)
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  • Journal Article Pessah IN, Seegal RF, Lein PJ, LaSalle J, Yee BK, Van de Water J, Berman RF. Immunologic and neurodevelopmental susceptibilities of autism. NeuroToxicology 2008;29(3):532-545. R833292 (2008)
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  • Journal Article Pessah IN, Lehmler HJ, Robertson LW, Perez CF, Cabrales E, Bose DD, Feng W. Enantiomeric specificity of (-)-2,2',3,3',6,6'-hexachlorobiphenyl toward ryanodine receptor types 1 and 2. Chemical Research in Toxicology 2009;22(1):201-207. R833292 (Final)
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  • Journal Article Pessah IN, Cherednichenko G, Lein PJ. Minding the calcium store: ryanodine receptor activation as a convergent mechanism of PCB toxicity. Pharmacology & Therapeutics 2010;125(2):260-285. R833292 (2009)
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  • Journal Article Phimister AJ, Lango J, Lee EH, Ernst-Russell MA, Takeshima H, Ma J, Allen PD, Pessah IN.
 Conformation-dependent stability of junctophilin 1 (JP1) and ryanodine receptor type 1 (RyR1) channel complex is mediated by their hyper-reactive thiols.
 Journal of Biological Chemistry 2007;282(12):8667-8677. R833292 (2007)
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  • Journal Article Qi L, Wang Y-F, He Y. A comparison of multiple imputation and fully augmented weighted estimators for Cox regression with missing covariates. Statistics in Medicine 2010;29(25):2592-2604. R833292 (Final)
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  • Journal Article Qiu H, Li N, Liu J-Y, Harris TR, Hammock BD, Chiamvimonvat N. Soluble epoxide hydrolase inhibitors and heart failure. Cardiovascular Therapeutics 2011;29(2):99-111. R833292 (Final)
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  • Journal Article Rose M, Bennett DH, Bergman A, Fangstrom B, Pessah IN, Hertz-Picciotto I. PBDEs in 2-5 year-old children from California and associations with diet and indoor environment. Environmental Science & Technology 2010;44(7):2648-2653. R833292 (2009)
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  • Journal Article Rossi CC, Van de Water J, Rogers SJ, Amaral DG. Detection of plasma autoantibodies to brain tissue in young children with and without autism spectrum disorders. Brain, Behavior, and Immunity 2011;25(6):1123-1135. R833292 (2011)
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  • Journal Article Samso M, Feng W, Pessah IN, Allen PD. Coordinated movement of cytoplasmic and transmembrane domains of RyR1 upon gating. PLoS Biology 2009;7(4):e85 (16 pp.). R833292 (2009)
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  • Journal Article Schmelzer KR, Inceoglu B, Kubala L, Kim IH, Jinks SL, Eiserich JP, Hammock BD. Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors. Proceedings of the National Academy of Sciences of the United States of America 2006;103(37):13646-13651. R833292 (Final)
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  • Journal Article Schmelzer KR, Wheelock AM, Dettmer K, Morin D, Hammock BD. The role of inflammatory mediators in the synergistic toxicity of ozone and 1-nitronaphthalene in rat airways.
 Environmental Health Perspectives 2006;114(9):1354-1360. R833292 (Final)
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  • Journal Article Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, Tassone F, Hertz-Picciotto I. Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiology 2011;22(4):476-485. R833292 (2011)
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  • Journal Article Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tassone F, Hertz-Picciotto I. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. American Journal of Clinical Nutrition 2012;96(1):80-89. R833292 (2009)
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  • Journal Article Senturk D, Nguyen DV. Partial covariate adjusted regression. Journal of Statistical Planning and Inference 2009;139(2):454-468. R833292 (Final)
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  • Journal Article Shearer GC, Newman JW, Hammock BD, Kaysen GA. Graded effects of proteinuria on HDL structure in nephrotic rats. Journal of the American Society of Nephrology 2005;16(5):1309-1319. R833292 (Final)
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  • Journal Article Shelton JF, Tancredi DJ, Hertz-Picciotto I. Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Research 2010;3(1):30-39. R833292 (2009)
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  • Journal Article Shelton JF, Hertz-Picciotto I, Pessah IN. Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environmental Health Perspectives 2012;120(7):944-951. R833292 (2012)
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  • Journal Article Smilowitz JT, Dillard CJ, German JB. Milk beyond essential nutrients: the metabolic food.
 Australian Journal of Dairy Technology 2005;60(2):77-83. R833292 (Final)
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  • Journal Article Sonneborn D, Park HY, Petrik J, Kocan A, Palkovicova L, Trnovec T, Nguyen D, Hertz-Picciotto I. Prenatal polychlorinated biphenyl exposures in eastern Slovakia modify effects of social factors on birthweight. Paediatric and Perinatal Epidemiology 2008;22(3):202-213. R833292 (Final)
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  • Journal Article Sonneborn D, Park HY, Babinska K, Palkovicova L, Trnovec T, Kocan A, Nguyen DV, Hertz-Picciotto I. Serum PCB concentrations in relation to locally produced food items in eastern Slovakia. Journal of Exposure Science & Environmental Epidemiology 2008;18(6):581-587. R833292 (2009)
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  • Journal Article Stamova BS, Apperson M, Walker WL, Tian Y, Xu H, Adamczy P, Zhan X, Liu D-Z, Ander BP, Liao IH, Gregg JP, Turner RJ, Jickling GC, Lit L, Sharp FR. Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood. BMC Medical Genomics 2009;2:49. R833292 (Final)
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  • Journal Article Stamova BS, Tian Y, Nordahl CW, Shen MD, Rogers S, Amaral DG, Sharp FR. Evidence for differential alternative splicing in blood of young boys with autism spectrum disorders. Molecular Autism 2013;4:30 (16 pp.). R833292 (2012)
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  • Journal Article Stamova B, Green PG, Tian Y, Hertz-Picciotto I, Pessah IN, Hansen R, Yang X, Teng J, Gregg JP, Ashwood P, Van de Water J, Sharp FR. Correlations between gene expression and mercury levels in blood of boys with and without autism. Neurotoxicity Research 2011;19(1):31-48. R833292 (2009)
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  • Journal Article Ta TA, Feng W, Molinski TF, Pessah IN. Hydroxylated xestospongins block inositol-1,4,5-trisphosphate-induced Ca2+ release and sensitive Ca2+-induced Ca2+ release mediated by ryanodine receptors. Molecular Pharmacology 2006;69(2):532-538. R833292 (Final)
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  • Journal Article Ta TA, Pessah IN. Ryanodine receptor type 1 (RyR1) possessing malignant hyperthermia mutation R615C exhibits heightened sensitivity to dysregulation by non-coplanar 2,2',3,5',6-pentachlorobiphenyl (PCB 95). NeuroToxicology 2007;28(4):770-779. R833292 (2007)
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  • Journal Article Ta TA, Koenig CM, Golub MS, Pessah IN, Qi L, Aronov PA, Berman RF. Bioaccumulation and behavioral effects of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) in perinatally exposed mice. Neurotoxicology and Teratology 2011;33(3):393-404. R833292 (2011)
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  • Journal Article Tabares-da Rosa S, Rossotti M, Carleiza C, Carrion F, Pritsch O, Ahn KC, Last JA, Hammock BD, Gonzalez-Sapienza G. Competitive selection from single domain antibody libraries allows isolation of high-affinity antihapten antibodies that are not favored in the llama immune response. Analytical Chemistry 2011;83(18):7213-7220. R833292 (2012)
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  • Journal Article Tassone F, Qi L, Zhang W, Hansen RL, Pessah IN, Hertz-Picciotto I. MAOA, DΒH and SLC6A4 variants in CHARGE: a case-control study of autism spectrum disorders. Autism Research 2011;4(4):250-261. R833292 (2011)
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  • Journal Article Tian Y, Green PG, Stamova B, Hertz-Picciotto I, Pessah IN, Hansen R, Yang X, Gregg JP, Ashwood P, Jickling G, Van de Water J, Sharp FR. Correlations of gene expression with blood lead levels in children with autism compared to typically developing controls. Neurotoxicity Research 2011;19(1):1-13. R833292 (2009)
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  • Journal Article Trnovec T, Dedík L, Jusko TA, Lancz K, Palkovicova L, Kocan A, Sovcikova E, Wimmerova S, Tihanyi J, Patayova H, Hertz-Picciotto I. Assessment of exposure to PCB 153 from breast feeding and normal food intake in individual children using a system approach model. Chemosphere 2011;85(11):1687-1693. R833292 (2012)
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  • Journal Article Ulu A, Davis BB, Tsai H-J, Kim I-H, Morisseau C, Inceoglu B, Fiehn O, Hammock BD, Weiss RH. Soluble epoxide hydrolase inhibitors reduce the development of atherosclerosis in apolipoprotein E-knockout mouse model. Journal of Cardiovascular Pharmacology 2008;52(4):314-323. R833292 (Final)
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  • Journal Article Van Meter KC, Christiansen LE, Hertz-Picciotto I, Azari R, Carpenter TE. A procedure to characterize geographic distributions of rare disorders in cohorts. International Journal of Health Geographics 2008;7:26. R833292 (Final)
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  • Journal Article Van Meter KC, Christiansen LE, Delwiche, LD, Azari R, Carpenter TE, Hertz-Picciotto I. Geographic distribution of autism in California: a retrospective birth cohort analysis. Autism Research 2010;3(1):19-29. R833292 (2009)
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  • Journal Article Verner MA, Sonneborn D, Lancz K, Muckle G, Ayotte P, Dewailly E, Kocan A, Palkovicova L, Trnovec T, Haddad S, Hertz-Picciotto I, Eggesbo M. Toxicokinetic modeling of persistent organic pollutant levels in blood from birth to 45 months of age in longitudinal birth cohort studies. Environmental Health Perspectives 2013;121(1):131-137. R833292 (2012)
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  • Journal Article Vogel CFA, Goth SR, Dong B, Pessah IN, Matsumura F. Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2,3-dioxygenase. Biochemical and Biophysical Research Communications 2008;375(3):331-335. R833292 (Final)
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  • Journal Article Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R. Residential proximity to freeways and autism in the CHARGE Study. Environmental Health Perspectives 2011;119(6):873-877. R833292 (2011)
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  • Journal Article Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB. In vitro fermentability of human milk oligosaccharides by several strains of bifidobacteria. Molecular Nutrition & Food Research 2007;51(11):1398-1405. R833292 (Final)
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  • Journal Article Wayman GA, Bose DD, Yang D, Lesiak A, Bruun D, Impey S, Ledoux V, Pessah IN, Lein PJ. PCB 95 modulates calcium-dependent signaling pathway responsible for activity-dependent dendritic growth. Environmental Health Perspectives 2012;120(7):1003-1009. R833292 (2012)
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  • Journal Article 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. R833292 (2012)
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  • Journal Article Wiest MM, German JB, Harvey DJ, Watkins SM, Hertz-Picciotto I. Plasma fatty acid profiles in autism: a case-control study. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2009;80(4):221-227. R833292 (2009)
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  • Journal Article Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral D, Van de Water J. Autoantibodies in autism spectrum disorders (ASD).
 Annals of the New York Academy of Sciences 2007;1107:79-91. R833292 (2007)
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  • Journal Article Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral DG, Van de Water J. Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders. Brain, Behavior, and Immunity 2009;23(1):64-74. R833292 (2008)
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  • Journal Article Wills S, Rossi CC, Bennett J, Martinez-Cerdeno V, Ashwood P, Amaral DG, Van de Water J. Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism. Molecular Autism 2011;2:5. R833292 (2011)
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  • Journal Article Woods R, Vallero RO, Golub MS, Suarez JK, Ta TA, Yasui DH, Chi LH, Kostyniak PJ, Pessah IN, Berman RF, LaSalle JM. Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. Human Molecular Genetics 2012;21(11):2399-2411. R833292 (2012)
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  • Journal Article Wu XM, Bennett DH, Lee K, Cassady DL, Ritz B, Hertz-Picciotto I. Feasibility of using web surveys to collect time-activity data. Journal of Exposure Science & Environmental Epidemiology 2012;22(2):116-125. R833292 (2012)
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  • Journal Article Wu X, Bennett DH, Lee K, Cassady DL, Ritz B, Hertz-Picciotto I. Longitudinal variability of time-location/activity patterns of population at different ages:a longitudinal study in California. Environmental Health 2011;10:80 (15 pp.). R833292 (2012)
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  • Journal Article Yakes EA, Arsenault JE, Islam MM, Hossain MB, Ahmed T, German JB, Gillies LA, Rahman AS, Drake C, Jamil KM, Lewis BL, Brown KH. Intakes and breast-milk concentrations of essential fatty acids are low among Bangladeshi women with 24-48-month-old children. British Journal of Nutrition 2011;105(11):1660-1670. R833292 (2012)
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  • Journal Article Yakes EA, Arsenault JE, Islam MM, Ahmed T, German JB, Drake C, Hossain MB, Lewis BL, Rahman AS, Jamil KM, Brown KH. Dietary intake of polyunsaturated fatty acids among breast-feeding and non-breast-feeding 24- to 48-month-old children in Bangladesh. Journal of Pediatric Gastroenterology and Nutrition 2011;52(3):351-359. R833292 (2012)
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  • Journal Article Yang D, Kim KH, Phimister AV, Bachstetter AD, Ward TR, Stackman RW, Mervis RF, Wisniewski AB, Klein SL, Kodavanti PRS, Anderson KA, Wayman G, Pessah IN, Lein PJ. Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats. Environmental Health Perspectives 2009;117(3):426-435. R833292 (Final)
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  • Journal Article Yang J, Dong H, Hammock BD. Profiling the regulatory lipids: another systemic way to unveil the biological mystery. Current Opinion in Lipidology 2011;22(3):197-203. R833292 (2012)
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  • Journal Article Yang T, Riehl J, Esteve E, Matthaei KI, Goth S, Allen PD, Pessah IN, Lopez JR. Pharmacologic and functional characterization of malignant hyperthermia in the R163C RyR1 knock-in mouse. Anesthesiology 2006;105(6):1164-1175. R833292 (2007)
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  • Journal Article Yang T, Allen PD, Pessah IN, Lopez JR. Enhanced excitation-coupled calcium entry in myotubes is associated with expression of RyR1 malignant hyperthermia mutations. 
Journal of Biological Chemistry 2007;282(52):37471-37478. R833292 (2007)
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  • Journal Article Zerbo O, Iosif AM, Delwiche L, Walker C, Hertz-Picciotto I. Month of conception and risk of autism. Epidemiology 2011;22(4):469-475. R833292 (2011)
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  • Journal Article Zhang X, Lv CC, Tian J, Miao RJ, Xi W, Hertz-Picciotto I, Qi L. Prenatal and perinatal risk factors for autism in China. Journal of Autism and Developmental Disorders 2010;40(11):1311-1321. R833292 (2009)
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  • Journal Article Zivkovic AM, German JB, Esfandiari F, Halsted CH. Quantitative lipid metabolomic changes in alcoholic micropigs with fatty liver disease. Alcoholism: Clinical & Experimental Research 2009;33(4):751-758. R833292 (Final)
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  • Journal Article Zivkovic AM, Wiest MM, Nguyen U, Nording ML, Watkins SM, German JB. Assessing individual metabolic responsiveness to a lipid challenge using a targeted metabolomic approach. Metabolomics 2009;5(2):209-218. R833292 (Final)
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  • Journal Article Zivkovic AM, German JB. Metabolomics for assessment of nutritional status. Current Opinion in Clinical Nutrition and Metabolic Care 2009;12(5):501-507. R833292 (Final)
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  • Journal Article Zivkovic AM, Telis N, German JB, Hammock BD. Dietary omega-3 fatty acids in the modulation of inflammation and metabolic health. California Agriculture 2011;65(3):106-111. R833292 (Final)
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  • Journal Article Zivkovic AM, German JB, Lebrilla CB, Mills DA. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proceedings of the National Academy of Sciences of the United States of America 2011;108(Suppl 1):4653-4658. R833292 (2012)
    R833292 (Final)
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  • Journal Article Zivkovic AM, Barile D. Bovine milk as a source of functional oligosaccharides for improving human health. Advances in Nutrition 2011;2(3):284-289. R833292 (2012)
    R833292 (Final)
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  • Journal Article Eltit JM, Li H, Ward CW, Molinski T, Pessah IN, Allen PD, Lopez JR. Orthograde dihydropyridine receptor signal regulates ryanodine receptor passive leak. Proceedings of the National Academy of Sciences of the United States of America2011;108(17):7046-7051. R833292 (2012)
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  • Journal Article Nordahl CW, Lange N, Li DD, Barnett LA, Lee A, Buonocore MH, Simon TJ, Rogers S, Ozonoff S, Amaral DG. Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders. Proceedings of the National Academy of Sciences of the United States of America 2011;108(50):20195-20200. R833292 (2012)
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  • Journal Article Shumway S, Thurm A, Swedo SE, Deprey L, Barnett LA, Amaral DG, Rogers SJ, Ozonoff S. Brief report: symptom onset patterns and functional outcomes in young children with autism spectrum disorders. Journal of Autism and Developmental Disorders 2011;41(12):1727-1732. R833292 (2012)
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  • Journal Article Cunningham CL, Martinez Cerdeno V, Navarro Porras E, Prakash AN, Angelastro JM, Willemsen R, Hagerman PJ, Pessah IN, Berman RF, Noctor SC. Premutation CGG-repeat expansion of the Fmr1 gene impairs mouse neocortical development. Human Molecular Genetics 2011;20(1):64-79. R833292 (2012)
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  • Journal Article Jusko TA, De Roos AJ, Schwartz SM, Lawrence BP, Palkovicova L, Nemessanyi T, Drobna B, Fabisikova A, Kocan A, Jahnova E, Kavanagh TJ, Trnovec T, Hertz-Picciotto I. Maternal and early postnatal polychlorinated biphenyl exposure in relation to total serum immunoglobulin concentrations in 6-month-old infants. Journal of Immunotoxicology 2011;8(1):95-100. R833292 (2012)
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  • Journal Article Wu XM, Bennett DH, Ritz B, Frost J, Cassady D, Lee K, Hertz-Picciotto I. 
Residential insecticide usage in northern California homes with young children.
 Journal of Exposure Science & Environmental Epidemiology 2011;21(4):427-436. R833292 (2012)
    R831540 (Final)
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  • Journal Article Ghosh R, Amirian E, Dostal M, Sram RJ, Hertz-Picciotto I. Indoor coal use and early childhood growth. Archives of Pediatrics & Adolescent Medicine 2011;165(6):492-497. R833292 (2012)
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  • Journal Article Hunsaker MR, Greco CM, Tassone F, Berman RF, Willemsen R, Hagerman RJ, Hagerman PJ. Rare intranuclear inclusions in the brains of 3 older adult males with fragile X syndrome: implications for the spectrum of fragile X-associated disorders. Journal of Neuropathology & Experimental Neurology 2011;70(6):462-469. R833292 (2012)
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  • Journal Article Rozga A, Hutman T, Young GS, Rogers SJ, Ozonoff S, Dapretto M, Sigman M. Behavioral profiles of affected and unaffected siblings of children with autism: contribution of measures of mother-infant interaction and nonverbal communication. Journal of Autism and Developmental Disorders 2011;41(3):287-301. R833292 (2012)
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  • Journal Article Bent S, Bertoglio K, Ashwood P, Bostrom A, Hendren RL. A pilot randomized controlled trial of omega-3 fatty acids for autism spectrum disorder. Journal of Autism Developmental Disorders 2011;41(5):545-554. R833292 (2012)
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  • Journal Article Bookman EB, McAllister K, Gillanders E, Wanke K, Balshaw D, Rutter J, Reedy J, Shaughnessy D, Agurs-Collins T, Paltoo D, Atienza A, Bierut L, Kraft P, Fallin MD, Perera F, Turkheimer E, Boardman J, Marazita ML, Rappaport SM, Boerwinkle E, Suomi SJ, Caporaso NE, Hertz-Picciotto I, Jacobson KC, Lowe WL, Goldman LR, Duggal P, Gunnar MR, Manolio TA, Green ED, Olster DH, Birnbaum LS for the NIH G × E Interplay Workshop participants. Gene-environment interplay in common complex diseases: forging an integrative model—recommendations from an NIH workshop. Genetic Epidemiology 2011;35(4):217-225. R833292 (2012)
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  • Journal Article Vivanti G, McCormick C, Young GS, Abucayan F, Hatt N, Nadig A, Ozonoff S, Rogers SJ. Intact and impaired mechanisms of action understanding in autism. Developmental Psychology 2011;47(3):841-856. R833292 (2012)
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  • Journal Article Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K, Lotspeich L, Croen LA, Ozonoff S, Lajonchere C, Grether JK, Risch N. Genetic heritability and shared environmental factors among twin pairs with autism. JAMA Psychiatry (formerly Archives of General Psychiatry). 2011;68(11):1095-1102. R833292 (2012)
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  • Journal Article Young GS, Rogers SJ, Hutman T, Rozga A, Sigman M, Ozonoff S. Imitation from 12 to 24 months in autism and typical development: a longitudinal Rasch analysis. Developmental Psychology 2011;47(6):1565-1578. R833292 (2012)
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  • Journal Article Critchfield JW, van Hemert S, Ash M, Mulder L, Ashwood P. The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterology Research and Practice 2011;2011:161358 (8 pp.). R833292 (2012)
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  • Journal Article Wu X, Apte MG, Maddalena R, Bennett DH. Volatile organic compounds in small- and medium-sized commercial buildings in California. Environmental Science & Technology 2011;45(20):9075-9083. R833292 (2012)
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  • Journal Article Hunsaker MR, Greco CM, Spath MA, Smits AP, Navarro CS, Tassone F, Kros JM, Severijnen LA, Berry-Kravis EM, Berman RF, Hagerman PJ, Willemsen R, Hagerman RJ, Hukema RK. Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice. Acta Neuropathologica 2011;122(4):467-479. R833292 (2012)
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  • Journal Article Hunsaker MR, von Leden RE, Ta BT, Goodrich-Hunsaker NJ, Arque G, Kim K, Willemsen R, Berman RF. Motor deficits on a ladder rung task in male and female adolescent and adult CGG knock-in mice. Behavioural Brain Research 2011;222(1):117-121. R833292 (2012)
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  • Journal Article Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L, Bryson S, Carver LJ, Constantino JN, Dobkins K, Hutman T, Iverson JM, Landa R, Rogers SJ, Sigman M, Stone WL. Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study. Pediatrics 2011;128(3):e488-e495. R833292 (2012)
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  • Journal Article Newschaffer CJ, Croen LA, Fallin MD, Hertz-Picciotto I, Nguyen DV, Lee NL, Berry CA, Farzadegan H, Hess HN, Landa RJ, Levy SE, Massolo ML, Meyerer SC, Mohammed SM, Oliver MC, Ozonoff S, Pandey J, Schroeder A, Shedd-Wise KM. Infant siblings and the investigation of autism risk factors. Journal of Neurodevelopmental Disorders 2012;4(1):7 (16 pp.). R833292 (2012)
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  • Journal Article Dutta SK, Mitra PS, Ghosh S, Zang S, Sonneborn D, Hertz-Picciotto I, Trnovec T, Palkovicova L, Sovcikova E, Ghimbovschi S, Hoffman EP. Differential gene expression and a functional analysis of PCB-exposed children: understanding disease and disorder development. Environment International 2012;40:143-154. R833292 (2012)
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  • Journal Article Jusko TA, Sonneborn D, Palkovicova L, Kocan A, Drobna B, Trnovec T, Hertz-Picciotto I. Pre- and postnatal polychlorinated biphenyl concentrations and longitudinal measures of thymus volume in infants. Environmental Health Prespectives 2012;120(4):595-600. R833292 (2012)
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  • Journal Article Hinde K, German JB. Food in an evolutionary context: insights from mother's milk. Journal of the Science of Food and Agriculture 2012;92(11):2219-2223. R833292 (2012)
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  • Journal Article van Thriel C, Westerink RH, Beste C, Bale AS, Lein PJ, Leist M. Translating neurobehavioural endpoints of developmental neurotoxicity tests into in vitro assays and readouts. Neurotoxicology 2012;33(4):911-924. R833292 (2012)
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  • Journal Article Ghosh R, Joad J, Benes I, Dostal M, Sram RJ, Hertz-Picciotto I. Ambient nitrogen oxides exposure and early childhood respiratory illnesses. Environment International 2012;39(1):96-102. R833292 (2012)
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  • Journal Article Mitra PS, Ghosh S, Zang S, Sonneborn D, Hertz-Picciotto I, Trnovec T, Palkovicova L, Sovcikova E, Ghimbovschi S, Hoffman EP, Dutta SK. Analysis of the toxicogenomic effects of exposure to persistent organic pollutants (POPs) in Slovakian girls: correlations between gene expression and disease risk. Environment International 2012;39(1):188-199. R833292 (2012)
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  • Journal Article Diep AA, Hunsaker MR, Kwock R, Kim K, Willemsen R, Berman RF. Female CGG knock-in mice modeling the fragile X premutation are impaired on a skilled forelimb reaching task. Neurobiology of Learning and Memory 2012;97(2):229-234. R833292 (2012)
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  • Journal Article Barrientos GC, Feng W, Truong K, Matthaei KI, Yang T, Allen PD, Lopez JR, Pessah IN. Gene dose influences cellular and calcium channel dysregulation in heterozygous and homozygous T4826I-RYR1 malignant hyperthermia-susceptible muscle. The Journal of Biological Chemistry 2012;287(4):2863-2876. R833292 (2012)
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  • Journal Article Cao Z, Hulsizer S, Tassone F, Tang HT, Hagerman RJ, Rogawski MA, Hagerman PJ, Pessah IN. Clustered burst firing in FMR1 premutation hippocampal neurons: amelioration with allopregnanolone. Human Molecular Genetics 2012;21(13):2923-2935. R833292 (2012)
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  • Journal Article Borthwell RM, Hunsaker MR, Willemsen R, Berman RF. Spatiotemporal processing deficits in female CGG KI mice modeling the fragile X premutation. Behavioural Brain Research 2012;233(1):29-34. R833292 (2012)
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  • Journal Article Sundekilde UK, Barile D, Meyrand M, Poulsen NA, Larsen LB, Lebrilla CB, German JB, Bertram HC. Natural variability in bovine milk oligosaccharides from Danish Jersey and Holstein-Friesian breeds. Journal of Agricultural and Food Chemistry 2012;60(24):6188-6196. R833292 (2012)
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  • Journal Article Bent S, Bertoglio K, Ashwood P, Nemeth E, Hendren RL. Brief report: hyperbaric oxygen therapy (HBOT) in children with autism spectrum disorder: a clinical trial. Journal of Autism Developmental Disorders 2012;42(6):1127-1132. R833292 (2012)
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  • Journal Article Lein PJ. Emerging concepts in neurotoxicology: models, mechanisms and modifying factors. NeuroToxicology 2012;33(3):516-517. R833292 (2012)
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  • Journal Article Yuen B, Boncompagni S, Feng W, Yang T, Lopez JR, Matthaei KI, Goth SR, Protasi F, Franzini-Armstrong C, Allen PD, Pessah IN. Mice expressing T4826I-RYR1 are viable but exhibit sex- and genotype-dependent susceptibility to malignant hyperthermia and muscle damage. FASEB Journal 2012;26(3):1311-1322. R833292 (2012)
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  • Journal Article Eltit JM, Bannister RA, Moua O, Altamirano F, Hopkins PM, Pessah IN, Molinski TF, López JR, Beam KG, Allen PD. Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca2+ channel and the type 1 ryanodine receptor. Proceedings of the National Academy of Sciences of the United States of America 2012;109(20):7923-7928. R833292 (2012)
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  • Journal Article Schebb NH, Ahn KC, Dong H, Gee SJ, Hammock BD. Whole blood is the sample matrix of choice for monitoring systemic triclocarban levels. Chemosphere 2012;87(7):825-827. R833292 (2012)
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  • Journal Article Braunschweig D, Golub MS, Koenig CM, Qi L, Pessah IN, Van de Water J, Berman RF. Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model. Journal of Neuroimmunology 2012;15;252(1-2):56-65. R833292 (2012)
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  • Journal Article Kaplan ES, Cao Z, Hulsizer S, Tassone F, Berman RF, Hagerman PJ, Pessah IN. Early mitochondrial abnormalities in hippocampal neurons cultured from Fmr1 pre-mutation mouse model. Journal of Neurochemistry 2012;123(4):613-621. R833292 (2012)
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  • Journal Article Coury DL, Ashwood P, Fasano A, Fuchs G, Geraghty M, Kaul A, Mawe G, Patterson P, Jones NE. Gastrointestinal conditions in children with autism spectrum disorder: developing a research agenda. Pediatrics 2012;130(Suppl 2):S160-S168. R833292 (2012)
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  • Journal Article Ozonoff S. Editorial perspective: autism spectrum disorders in DSM-5--an historical perspective and the need for change. Journal of Child Psychology and Psychiatry 2012;53(10):1092-1094. R833292 (2012)
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  • Journal Article Winarni TI, Chonchaiya W, Sumekar TA, Ashwood P, Morales GM, Tassone F, Nguyen DV, Faradz SM, Van de Water J, Cook K, Hamlin A, Mu Y, Hagerman PJ, Hagerman RJ. Immune-mediated disorders among women carriers of fragile X premutation alleles. American Journal of Medical Genetics Part A 2012;158A(10):2473-2481. R833292 (2012)
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  • Journal Article Kim IH, Nishi K, Kasagami T, Morisseau C, Liu JY, Tsai HJ, Hammock BD. Biologically active ester derivatives as potent inhibitors of the soluble epoxide hydrolase. Bioorganic & Medicinal Chemistry Letters 2012;22(18):5889-5892. R833292 (2012)
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  • Journal Article Fatemi SH, Aldinger KA, Ashwood P, Bauman ML, Blaha CD, Blatt GJ, Chauhan A, Chauhan V, Dager SR, Dickson PE, Estes AM, Goldowitz D, Heck DH, Kemper TL, King BH, Martin LA, Millen KJ, Mittleman G, Mosconi MW, Persico AM, Sweeney JA, Webb SJ, Welsh JP. Consensus paper: pathological role of the cerebellum in autism. Cerebellum 2012;11(3):777-807. R833292 (2012)
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  • Journal Article Ozonoff S. DSM-5 and autism spectrum disorders--two decades of perspectives from the JCPP. Journal of Child Psychology and Psychiatry 2012;53(9):e4-e6 (editorial). R833292 (2012)
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  • Journal Article Onore C, Van de Water J, Ashwood P. Decreased levels of EGF in plasma of children with autism spectrum disorder. Autism Research and Treatment 2012;2012:205362 (4 pp.). R833292 (2012)
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  • Journal Article Clifton MS, Wargo JP, Weathers WS, Colon M, Bennett DH, Tulve NS. Quantitative analysis of organophosphate and pyrethroid insecticides, pyrethroid transformation products, polybrominated diphenyl ethers and bisphenol A in residential surface wipe samples. Journal of Chromatography A 2013;1273:1-11. R833292 (2012)
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  • Journal Article Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic related air pollution, particulate matter, and autism. JAMA Psychiatry 2013;70(1):71-77. R833292 (2012)
    R835441 (2017)
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  • Journal Article Zerbo O, Iosif A-M, Walker C, Ozonoff S, Hansen RL, Hertz-Picciotto I. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study. Journal of Autism and Developmental Disorders 2013;43(1):25-33. R833292 (2012)
    R833292 (Final)
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  • Journal Article Breece E, Paciotti B, Nordahl CW, Ozonoff S, Van de Water JA, Rogers SJ, Amaral D, Ashwood P. Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors. Brain, Behavior, and Immunity 2013;31:69-75. R833292 (2012)
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  • Journal Article Tassone F, Choudhary NS, Tassone F, Durbin-Johnson B, Hansen R, Hertz-Picciotto I, Pessah I. Identification of expanded alleles of the FMR1 gene in the CHildhood Autism Risks from Genes and Environment (CHARGE) study. Journal of Autism and Developmental Disorders 2013;43(3):530-539. R833292 (2012)
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  • Journal Article Goines PE, Ashwood P. Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment. Neurotoxicology and Teratology 2013;36:67-81. R833292 (2012)
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  • Journal Article Schwartzer JJ, Koenig CM, Berman RF. Using mouse models of autism spectrum disorders to study the neurotoxicology of gene-environment interactions. Neurotoxicology and Teratology 2013;36:17-35. R833292 (2012)
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  • Supplemental Keywords:

    autism, case control study, gene-environment interactions, immunotoxicity, autoimmunity, immunology, PCBs, PBDEs, autoantibodies, mechanisms, dendritic cells, neuronal cell development, hippocampal excitability, seizures, mercury, biostatistics, gene selection, Scientific Discipline, Health, Genetics, Health Risk Assessment, Risk Assessments, Biochemistry, children's health, developmental neurotoxicology, ecotoxicogenomics, developmental effects, genetic analysis

    Progress and Final Reports:

    Original Abstract
  • 2007 Progress Report
  • 2008 Progress Report
  • 2009 Progress Report
  • 2010 Progress Report
  • 2011 Progress Report
  • 2012 Progress Report
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R833292C001 PROJECT 1: Environmental Epidemiology of Autism
    R833292C002 PROJECT 2: Immunological Susceptibility in Autism
    R833292C003 PROJECT 3: Models of Neurosusceptibility