The Untargeted Research Resources (URR) of the NEALE will provide advanced untargeted analytical chemical profiling to support the children?s health research community for environmental factors related to health and disease. The URR will use high-resolution metabolomics (HRM) capabilities developed at Emory and currently in use to support exposome research. HRM uses ultra-high resolution mass spectrometry with rigorous standard operating procedures, dual chromatography and analysis with 5 technical replicates to support routine measurement of >10,000 chemicals in biological samples. This includes metabolites from most human metabolic pathways, host microbiome, infectious agents and dietary, environmental and behavioral exposures. The methods have been applied to many biologic materials, including plasma, urine, and other body fluids, cells, biopsies, foods and stool samples. Existing data for 15,000 human plasma samples, including interventional studies and more than 20 disease states, provide secure reference data to address common and uncommon chemical variations expected to occur in the early life exposome. Objective 1. The URR will provide untargeted HRM to support the children?s health research community. Samples will be extracted and analyzed by dual chromatography (HILIC, positive ESI; C18 negative ESI) HRM. Objective 2. In conjunction with children?s health research users and biostatistical resources core, biostatistics and bioinformatics analyses will be performed to obtain metabolome-wide association study (MWAS) of defined exposure, phenotypic variable or other characteristic of specific interest. Objective 3. Provide global bioeffect monitoring through pathway enrichment analyses from untargeted HRM. Objective 4. Confirmation of chemical identities and quantification will be provided for unidentified chemicals of highest priority. Objective 5. Further method development to enhance quantitative measurement of low abundance environmental chemicals, including advanced methods to improve coverage of chemical space, measurement of chemical congeners, and standardization of the chemical exposome. The URR will provide high quality, extensive coverage of environmental chemicals and metabolic responses in reliable forms for future data-mining and exposome research. In combination with the other resources of NEALE, this support structure will provide an important facility to advance the research initiatives of the children?s health research community.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Resource-Related Research Multi-Component Projects and Centers Cooperative Agreements (U2C)
Project #
1U2CES026560-01
Application #
9062182
Study Section
Special Emphasis Panel (ZES1-LWJ-J (UC))
Project Start
2015-09-30
Project End
2019-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
1
Fiscal Year
2015
Total Cost
$1,591,708
Indirect Cost
$559,468
Name
Emory University
Department
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Niedzwiecki, Megan M; Samant, Pradnya; Walker, Douglas I et al. (2018) Human Suction Blister Fluid Composition Determined Using High-Resolution Metabolomics. Anal Chem 90:3786-3792
Wright, Robert O; Teitelbaum, Susan; Thompson, Claudia et al. (2018) The child health exposure analysis resource as a vehicle to measure environment in the environmental influences on child health outcomes program. Curr Opin Pediatr 30:285-291
Smirnov, Aleksandr; Jia, Wei; Walker, Douglas I et al. (2018) ADAP-GC 3.2: Graphical Software Tool for Efficient Spectral Deconvolution of Gas Chromatography-High-Resolution Mass Spectrometry Metabolomics Data. J Proteome Res 17:470-478
Chandler, Joshua D; Horati, Hamed; Walker, Douglas I et al. (2018) Determination of thiocyanate in exhaled breath condensate. Free Radic Biol Med 126:334-340
Frediani, Jennifer K; Naioti, Eric A; Vos, Miriam B et al. (2018) Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among U.S. adolescents and adults: an association modified by race/ethnicity, NHANES 2005-2014. Environ Health 17:6
Hu, Xin; Chandler, Joshua D; Park, Soojin et al. (2018) Low-dose cadmium disrupts mitochondrial citric acid cycle and lipid metabolism in mouse lung. Free Radic Biol Med 131:209-217
Johnson, Caroline H; Athersuch, Toby J; Collman, Gwen W et al. (2017) Yale school of public health symposium on lifetime exposures and human health: the exposome; summary and future reflections. Hum Genomics 11:32
Wolff, Mary S; Buckley, Jessie P; Engel, Stephanie M et al. (2017) Emerging exposures of developmental toxicants. Curr Opin Pediatr 29:218-224
Uppal, Karan; Walker, Douglas I; Liu, Ken et al. (2016) Computational Metabolomics: A Framework for the Million Metabolome. Chem Res Toxicol 29:1956-1975
Jones, Dean P (2016) Hydrogen peroxide and central redox theory for aerobic life: A tribute to Helmut Sies: Scout, trailblazer, and redox pioneer. Arch Biochem Biophys 595:13-8

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