Title: Application of adductomics for investigating associations between the environment and children’s health

Biography:

William E Funk is an Assistant Professor in the Department of Preventive Medicine at Northwestern University and an Associate Member of the Robert H. Lurie Comprehensive Cancer Center.

Abstract

Periods of fetal, infant and early childhood development are remarkably vulnerable to environmental hazards and exposures to toxic chemicals during these critical windows of susceptibility have been linked with disease, disabilities and adverse health in childhood and across the entire life span. As a result, identifying new integrative exposure biomarkers associated with early-life development is of paramount importance. In this study we focused on exposures to small reactive chemicals in blood (i.e., electrophiles). Electrophiles are produced through metabolic processes such as oxidative stress and also have exogenous sources from exposure to toxicants in the environment, thus they represent a broad and important component of the human exposome. However, because electrophiles are short lived in the blood they cannot normally be measured in vivo, which has motivated our group to measure adducts (addition products) that are formed with abundant of blood proteins. While targeted adducts have been measured as exposure biomarkers for decades, here we present a novel untargeted biomarker approach (i.e., adductomics) for mapping the childhood adductome to investigate links between the environment and children’s health. Adductomics is particularly well suited for these investigations because: (1) it captures an integration of exposures occurring during critical periods of development, (2) it captures exposures to both exogenous and endogenous chemicals that can act as environmental triggers and provide insights into underlying biological mechanisms, respectively and (3) can be performed using minimally-invasive bio-specimens, such as cord blood and dried blood spot (DBS) samples. Untargeted discovery experiments were first performed using human serum albumin isolated from plasma samples and enriched to characterize the childhood adductome. We then applied a targeted multiplexed assay to quantify adduct panels in DBS samples, as a minimally-invasive strategy to extend the application of adductomics to population-level research.