The Analytical core will provide state-of-the-art analyses that are of high priority to CCEH projects that link chemical exposures with clinical and epidemiological data (Project 1), epigenetic data (Project 2), immunological data (Project 3), and mechanistic data from human neurons (Project 4). Analytical Core will use its extensive experience in analytical chemistry to develop and validate highly sensitive and specific methods to quantitate target compounds in small volumes of plasma from mothers and children, in breast milk, and in urine. Specifically, the Analytical Core will serve center projects by conducting analyses on complex biological samples matrices to identify xenobiotic pollutants that are known or suspected of being developmental neurotoxicants and immunotoxicants, in human epidemiological studies and/or in animal models. Quantitative results will be provided to all CCEH Projects where they will be evaluated in the context of ASD risk, genomic and methylomic interactions, cytokine profiles and their ability to alter Ca^'^-dependent signaling pathways in human neurons and immune cells. The Core's three main objectives are: Objective 1: Provide general analytical support for efficient processing and extraction of small sample volumes archived in the CCEH biobank. Objective 2: Undertake highly sensitive and quantitative analytical chemistry techniques to determine concentrations of polybrominated diphenyl ether (PBDE), polychlorinated biphenyl (PCB), and perfluorinated compounds (PFCs) congener patterns present in maternal serum and pyrethroid pesticide metabolites in urine of women at high risk for giving birth to an autistic child participating in the MARBLES study, and those found in children and their mother participating in CHARGE Objective 3: Develop and implement new analytical techniques to measure. This will include the development of: 3.1. PBDE and PCB congener profiles in the same extracts;and 3.2. Hydroxylated PBDE and PCB (OH-PBDE and OH-PCB) metabolites in the same extracts.
The Analytical Core will provide essential services to all Projects, which all rely on accurate exposure data. This Core will generate the first detailed congener-level assessment of xenobiotic exposures in a wellstudied longitudinal cohort at high risk for autism, accurately quantitate xenobiotics in small volume specimens by modifying extraction and detection methods, and identify lead compounds which will become instrumental to all scientific projects of the Center.
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|Sethi, S; Chen, X; Kass, P H et al. (2017) Polychlorinated biphenyl and polybrominated diphenyl ether profiles in serum from cattle, sheep, and goats across California. Chemosphere 181:63-73|
|Dunaway, Keith; Goorha, Sarita; Matelski, Lauren et al. (2017) Dental Pulp Stem Cells Model Early Life and Imprinted DNA Methylation Patterns. Stem Cells 35:981-988|
|Aschner, Michael; Ceccatelli, Sandra; Daneshian, Mardas et al. (2017) Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use. ALTEX 34:49-74|
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|Meltzer, Amory; Van de Water, Judy (2017) The Role of the Immune System in Autism Spectrum Disorder. Neuropsychopharmacology 42:284-298|
|Sethi, Sunjay; Keil, Kimberly P; Chen, Hao et al. (2017) Detection of 3,3'-Dichlorobiphenyl in Human Maternal Plasma and Its Effects on Axonal and Dendritic Growth in Primary Rat Neurons. Toxicol Sci 158:401-411|
|Bal-Price, Anna; Lein, Pamela J; Keil, Kimberly P et al. (2017) Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity. Neurotoxicology 59:240-255|
|Holland, Erika B; Feng, Wei; Zheng, Jing et al. (2017) An Extended Structure-Activity Relationship of Nondioxin-Like PCBs Evaluates and Supports Modeling Predictions and Identifies Picomolar Potency of PCB 202 Towards Ryanodine Receptors. Toxicol Sci 155:170-181|
|Edmiston, Elizabeth; Ashwood, Paul; Van de Water, Judy (2017) Autoimmunity, Autoantibodies, and Autism Spectrum Disorder. Biol Psychiatry 81:383-390|
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