(Overall) This proposal is to establish a Superfund Center at the University of Louisville. This Center will support research on the cardiometabolic effects of volatile organic chemicals (VOCs) that are of high relevance to the Superfund Program. Center investigators will conduct mode-of-action research to unravel critical pathways of toxicity and to identify toxicological end-points (cardiometabolic changes) of chemicals (VOCs) found at Superfund and related sites. Using high throughput metabolomic and mass spectrometry approaches, animal experiments and human population studies, Center investigations will aid in the discovery and validation of novel biomarkers of both exposure and cardiometabolic injury that would lay the foundation for future remediation strategies. These studies will employ state-of-the-art tools to develop pollutant atmospheres for animal exposure and to measure unique and sensitive biological endpoints reflective of cardiometabolic injury. In addition, work supported by the Center will lead to the development of new methods and devices for quantifying atmospheric levels of VOCs that will employ advanced technologies and offer precise, but low-cost measurements of hazardous waste sites. The major objectives of the Center are to conduct state-of-the-art research on the cardiometabolic toxicity of VOCs and to determine how they affect cardiometabolic disease (CMD) prevalence and severity in exposed populations. These studies will be complemented by mode-of-action mechanistic studies in animals to identify the molecular and cellular mechanisms that contribute to VOC toxicity. Center investigators will also identify specific conditions such as nutritional status and obesity and increase susceptibility to VOC toxicity and test therapeutic interventions that can attenuate acute and chronic cardiometabolic effects of VOC exposures. The findings of these studies will contribute to both the discovery and the validation of sensitive and robust biomarkers that could be used to assess the extent of exposure, metabolism and toxicity. Center investigators will create new technologies for detecting VOCs at low environmental levels to enable future exposure assessment activities. Senior Center members will educate and train junior investigators, graduate students and post-doctoral Fellows in the field of environmental science, and promote relevant community awareness and participation to enhance mutual bidirectional understanding of exposure risk and the health effects of exposure. The findings and discoveries of the Center will be transferred to affected communities, end users in public and private sectors, and other stakeholders. For future use and analysis, all samples of human and animal tissues and all data collected during Center investigations will be stored in a computer-coded biorepository. Collectively, Center activities will lead to rigorous evaluation and better understanding of the effects of these hazardous chemicals on obesity, diabetes and cardiovascular disease.

Public Health Relevance

This proposal is to establish a Center to support research on the health effect of hazardous Superfund chemicals. Work in this Center will help in evaluating the health impact of several hazardous chemicals that are present in the environment and in understanding how exposure to chemicals could contribute to the risk and development of obesity, diabetes and heart disease, which despite recent medical advances, remain the leading causes of death worldwide.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES023716-04
Application #
9904675
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Carlin, Danielle J
Project Start
2017-09-01
Project End
2022-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Louisville
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Lang, Anna L; Beier, Juliane I (2018) Interaction of volatile organic compounds and underlying liver disease: a new paradigm for risk. Biol Chem 399:1237-1248
Riggs, Daniel W; Yeager, Ray A; Bhatnagar, Aruni (2018) Defining the Human Envirome: An Omics Approach for Assessing the Environmental Risk of Cardiovascular Disease. Circ Res 122:1259-1275
Li, Mingxiao; Li, Qi; Nantz, Michael H et al. (2018) Analysis of Carbonyl Compounds in Ambient Air by a Microreactor Approach. ACS Omega 3:6764-6769
Hein, David W; Zhang, Xiaoyan; Doll, Mark A (2018) Role of N-acetyltransferase 2 acetylation polymorphism in 4, 4'-methylene bis (2-chloroaniline) biotransformation. Toxicol Lett 283:100-105
Hein, David W; Fakis, Giannoulis; Boukouvala, Sotiria (2018) Functional expression of human arylamine N-acetyltransferase NAT1*10 and NAT1*11 alleles: a mini review. Pharmacogenet Genomics 28:238-244
Liang, Yaqin; Lang, Anna L; Zhang, Jian et al. (2018) Exposure to Vinyl Chloride and Its Influence on Western Diet-Induced Cardiac Remodeling. Chem Res Toxicol 31:482-493
Lang, Anna L; Chen, Liya; Poff, Gavin D et al. (2018) Vinyl chloride dysregulates metabolic homeostasis and enhances diet-induced liver injury in mice. Hepatol Commun 2:270-284
Xie, Zhenzhen; Ramakrishnam Raju, Mandapati V; Stewart, Andrew C et al. (2018) Imparting sensitivity and selectivity to a gold nanoparticle chemiresistor through thiol monolayer functionalization for sensing acetone. RSC Adv 8:35618-35624
Ramana, Kota V; Srivastava, Sanjay; Singhal, Sharad S (2017) Lipid Peroxidation Products in Human Health and Disease 2016. Oxid Med Cell Longev 2017:2163285
Ramana, Kota V; Srivastava, Sanjay; Reddy, Aramati B M (2016) Immune, Inflammatory, and Oxidative Responses in Cardiovascular Complications. Oxid Med Cell Longev 2016:6858402

Showing the most recent 10 out of 11 publications