Project 1 - VOC's and Cardiometabolic Injury

The overall goal of this project is to evaluate the influence of volatile organic compounds (VOCs) on cardiometabolic disease (CMD). The working hypothesis is that exposure to the Superfund VOCs, including trichloroethylene (TCE), xylene, benzene, and acrolein, exacerbates/induces insulin resistance and low-grade inflammation, leading to a cascade of events that accelerate CMD development and exacerbate cardiovascular disease (CVD) risk. To test this hypothesis, Project 1 will enroll 500 participants with different levels of VOC exposure to a) Determine the impact of VOC exposure on insulin resistance in a prospective longitudinal study. We will determine whether VOC exposure at baseline is associated with increased insulin resistance (HOMA-IR; primary outcome) and CMD risk (secondary outcome); b) Examine the influence of VOC exposure on cardiovascular and fatty liver disease (FLD) prevalence and progression.  Biomarkers of exposures (urinary metabolites of VOCs) and subclinical cardiovascular injury, CVD risk, and FLD will be measured at baseline, 18 and 36 months. We will evaluate how VOCs and/or residential proximity to the Superfund site and/or other industrial emissions affect the progression of various indices of CVD injury and FLD risk in the target population and how these effects differ from those due to background VOC exposures in urban residential locations.

Project 2 - Molecular and Cellular Mechanisms of Cardiometabolic Toxicity of VOCs

Obesity and T2D leading to cardiovascular disease (CVD) and fatty liver disease (FLD) are rapidly growing global health crises. The underlying cause of obesity and type 2 diabetes (T2D) is the diminution of the insulin sensitivity of target tissues, but the mechanisms are unclear. The overallgoal of this pre-clinical project is to examine the plausibility that volatile organic compounds (VOCs) induce/exacerbate cardiometabolic disease(CMD), and to delineate the underlying molecular mechanisms. We will examine how dose, duration, and sex affect endothelial function, insulin resistance, and CMD in adult mice exposed to representative VOCs (e.g. benzene, trichloroethylene, vinyl chloride, 1,3 butadiene, acrolein, etc.). In each exposure protocol, we will measure urinary metabolites of VOCs to quantify body burden. To elucidate the molecular mechanisms of VOC-induced insulin resistance and endothelial function and injury, we will examine how VOCs trigger endoplasmic reticulum (ER)-stress and induce unfolded protein response (UPR).  We will measure vascular, adipose tissue, and hepatic ER- stress and determine its relationship to changes in endothelial function and insulin sensitivity in VOC-exposed mice.

Project 3 - Development of Ultrasensitive Devices for VOC Measurement

The objective of this environmental science project is to develop low-cost silicon micropreconcentrator and microsensor array chip technologies for quantitative analysis of trace (ppbv to pptv) VOCs in air. The approach is to investigate chemoselective micropreconcentrators for capture of target VOCs by chemical reactions and physical micropreconcentrators for preconcentration of weakly polar and non-polar VOCs, and to develop gas sensor arrays for measuring the concentrations of target VOCs in air. This project will provide tools and methods for quantitative analysis of VOCs and will strengthen Projects 1 and 2 to investigate the effects of these contaminants on CMD. The outcome of this research is directly linked to high-priority national homeland security, air quality monitoring and healthcare issues.


Project 4 - Characterizing Urban-and Finer-Scale Spatial Variability for Select VOC Superfund Compounds

 The goal of this project is to examine the spatiotemporal variability of VOCs in urban residential neighborhoods, superfund sites and industrial areas. Mobile monitoring using a newly designed portable gas chromatograph (GC) will be employed to collect air quality data and Land use regression (LUR) and air quality dispersion modeling will be used for assessing spatiotemporal variability. These studies will be complemented with continuous stationary monitoring for select VOCs in three neighborhoods. We will also examine spatial relationships between greenness (vegetation density) and the concentration of select VOCs using the land use regression models adjusted for local emissions. This project will provide new reagents and approaches VOC analysis, which along with the analyses of urinary metabolites of VOCs will be critical is examining the effect of VOCs on cardiometabolic disease.