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Principal Investigator: Donghai Liang
Organization: EMORY UNIVERSITY
Fiscal Year: 2024
Award: $654,756
Funding agency: National Institute of Environmental Health Sciences
PROJECT SUMMARY
Exposures to prenatal traffic-related air pollution (TRAP), a primary contributor to urban air pollution, have
been linked to adverse birth outcomes including preterm birth (PTB). Notably, communities of color, especially
African American people, are disproportionately exposed to high TRAP levels and experience elevated rates of
PTB. The mechanisms underlying how maternal TRAP exposures may affect birth outcomes and shape child
health disparities are still largely unknown, due, in part, to substantial challenges in accurately characterizing
internal dose and biological responses to TRAP. Through the advancement in high-throughput analytical
techniques and new bioinformatics methods, our work and the work of others have demonstrated that several
omics platforms can be used in concert to identify sensitive biological signals associated with exogenous
TRAP exposures and PTB. Existing studies, including our own, have been limited in refined exposure
characterization, sample size (limiting ability to detect effects), focusing on a single exposure without much
attention to mixture, and, most importantly, did not examine the specific mechanistic roles of each molecule
from different omics layers and how they bridge the gap from TRAP exposures to PTB. To address these
critical knowledge gaps, we propose the Omics and Mixtures Integration on Traffic exposure and Preterm Birth
(OMIT-PTB) study to integrate and analyze longitudinal multi-omics data, spanning the maternal epigenome,
metabolome, and microbiome, to characterize the molecular connections between maternal exposures to
TRAP and PTB. Our innovative OMIT-PTB proposal will leverage the Atlanta African American Maternal-Child
Cohort, an exceptionally phenotyped prospective pregnancy cohort. We will conduct state-of-art multi-omics
profiling and integration during early and late pregnancy, innovative mixture analyses, and advanced
assessment of cumulative and short-term exposures to TRAP on 700 pregnant people in this cohort.
Specifically, we will conduct independent epigenome- (Aim 1), multi-stage metabolome- (Aim 2), and
microbiome- (Aim 3) wide association studies to identify biological markers and pathways associated with
prenatal TRAP exposures. Using advanced bioinformatic tools, we will conduct both a posteriori integration
(Aim 4a) and a priori integration (Aim 4b) to simultaneously analyze multi-omics data to investigate the
molecular connections between TRAP and PTB. The OMIT-PTB study will, for the first time, provide novel
insights and comprehensive information on signatures of systemic biological perturbation linking TRAP
exposures to PTB, leading to the identification of biological signals and markers (i.e., validated DNA
methylation pattern at CpG sites, metabolites and metabolic pathways, microbial taxa and community types).
These findings will contribute to elucidating potentially sensitive TRAP biomarkers and preclinical indicators for
PTB - a meaningful step for defining novel intervention strategies to mitigate TRAP exposure risk and improve
birth and health outcomes in exposed mothers and children.
Terms: <0-11 years old><Address><Affect><African American><African American group><African American individual><African American people><African American population><African Americans><Afro American><Afroamerican><Air Pollution><Attention><Bio-Informatics><Bioinformatics><Biological><Biological Markers><Biological Monitoring><Birth><C-reactive protein><Cell Communication and Signaling><Cell Signaling><Child><Child Health><Child Youth><Children (0-21)><Clinical><Color><Communities><Complex><DNA Methylation><Data><Detection><Disease><Disorder><Dose><Endogenous Nitrate Vasodilator><Endothelium-Derived Nitric Oxide><Environmental Health><Environmental Health Science><Exhalation><Exhaling><Experimental Models><Exposure to><Future><GI microbiome><Gases><Gestation><Health><Health Benefit><Inflammation><Inflammatory><Intervention><Intervention Strategies><Intracellular Communication and Signaling><Investigators><Knowledge><Late pregnancy><Link><Maps><Maternal Exposure><Measurement><Mediating><Metabolic Pathway><Methods><Modality><Modeling><Molecular><Mononitrogen Monoxide><Mothers><Multiomic Data><Nitric Oxide><Nitrogen Monoxide><Nitrogen Protoxide><Outcome><Oxidative Stress><Participant><Parturition><Pathway interactions><Persons><Phenotype><Pregnancy><Premature Birth><Prematurely delivering><Preterm Birth><Process><Proteins, specific or class, C-reactive><Public Health><Research Personnel><Researchers><Resolution><Respiratory Expiration><Risk><Risk Assessment><Risk Reduction><Role><Sample Size><Shapes><Signal Transduction><Signal Transduction Systems><Signaling><Site><Techniques><Time><Toxic effect><Toxicities><Work><adverse birth outcomes><analyzing longitudinal><bio-informatics tool><bio-markers><bioinformatics tool><biologic><biologic marker><biological signal transduction><biomarker><biomonitoring><cohort><cytokine><data integration><digestive tract microbiome><disparity in health><early pregnancy><endothelial cell derived relaxing factor><enteric microbiome><epigenome><experience><exposed in utero><feature selection><fetal exposure><gastrointestinal microbiome><gut microbiome><gut-associated microbiome><health disparity><improved><in utero exposure><innovate><innovation><innovative><insight><interventional strategy><intestinal biome><intestinal microbiome><intra-uterine environmental exposure><intrauterine environmental exposure><kids><longitudinal analysis><metabolism measurement><metabolome><metabolomics><metabonome><metabonomics><methylation pattern><microbial><microbiome><multidisciplinary><multiomics><multiple omic data><multiple omics><novel><panomics><particle><pathway><pollutant><potential biological marker><potential biomarker><pre-clinical><preclinical><pregnant><premature childbirth><premature delivery><prenatal><prenatal exposure><prenatally exposed><preterm delivery><prospective><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><resolutions><response><risk-reducing><social role><socio-economic><socio-economically><socioeconomically><socioeconomics><specific biomarkers><toxicant><traffic-related air pollution><unborn><vaginal biome><vaginal microbiome><youngster>