Project Summary The Research Support Core (RSC) will provide a wide range of high quality quantitative analytical technology platforms spanning metabolomics, epigenomics, transcriptomics, and proteomics. The RSC leader is Dr. Dean P. Edwards, Executive Director of the Advanced Technology Cores at BCM. The RSC co-leader is Dr. Nagireddy Putluri, who also serves as director of the Metabolomics Core and is a recognized leader in mass spectrometry- based metabolomics profiling. The RSC has the following specific aims. AIM 1 Will effectively support the Superfund projects with cutting edge quantitative multi-omics technologies. Established Core technologies available includes mass spectrometry-based targeted and unbiased metabolomics, unbiased proteomic profiling by mass spectrometry, targeted proteomics by antibody-based reverse phase protein array (RPPA) and genomics platforms such as whole genome sequencing, transcriptomics by RNA-seq, smallRNA sequencing and epigenetics by ChIP-Seq. RSC support will include intellectual input from faculty level Core Directors for consultation and experimental design, hosting of advanced instrumentation, executing state-of-the-art analytical procedures by research staff of Cores and processing and analysis of “omics” data sets. RSC technology platforms will be used primarily in Projects 2, 3 and 4 to identify biomarkers and molecular signatures of polycyclic aromatic hydrocarbon (PAH) exposures associated with preterm birth (PTB) and to define the molecular mechanisms underlying the potentiating effects of PAH and its derivatives on chronic lung disease/bronchopulmonary dysplasia (BPD) and neurobehavioral deficits in experimental models and in human studies. The metabolomics core will additionally be instrumental for measuring and quantification of PAH and its metabolites by GC-MS as a standard for development of more sensitive and less sophisticated assays in Projects 1 and 2. AIM 2 Will continuously work with Project leaders and investigators to develop, validate, and deploy novel methods during the course of the grant that are not currently standard Core procedures. This will initially include MS identification of novel PAH derivatives and metabolites, and unbiased metabolomics profiling, epigenetic profiling of histone modifications and chromatin modifying enzymes by RPPA, genome-wide DNA methylation by bisulfite sequencing and Redox proteomics by MS methods. AIM 3 Will train investigators in designing, executing, and interpreting results of the state-of-the-art analytical techniques conducted by the RSC. This will be accomplished by providing tutorials, workshops and some hands-on opportunities for principle investigators of the Superfund grant and their post-doctoral and graduate student trainees. The ultimate goal of the RSC is to provide cutting-edge technical and the best quality scientific solutions available for the Superfund investigators for use in their Aims of understanding PAH exposures at molecular mechanistic and genetic levels.

Project Narrative Pregnant women, living in the vicinity of superfund sites, who may be exposed to polyclic aromatic hydrocarbons (PAHs) that emanate from these sites, are at a higher risk for preterm delivery. We hypothesize that prenatal PAH exposure will exacerbate the effects of postnatal supplemental oxygen in preterm neonates. Accomplishments of the aims of this project should be beneficial to stakeholders such as EPA and ASTDR, as we will be able to extrapolate the doses we give in animals to humans who might be exposed to PAHs.