Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Internet Explorer is no longer a supported browser.

This website may not display properly with Internet Explorer. For the best experience, please use a more recent browser such as the latest versions of Google Chrome, Microsoft Edge, and/or Mozilla Firefox. Thank you.

Your Environment. Your Health.


Export to Word (
Principal Investigator: Knuckles, Travis Lee
Institute Receiving Award West Virginia University
Location Morgantown, WV
Grant Number R15ES028005
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 15 Aug 2017 to 14 Aug 2021
DESCRIPTION (provided by applicant): The production of shale gas, and the development of wells using horizontal drilling and hydraulic fracturing technology, is a major driver of the U.S. economy. The process of preparing well pads to completion of the work creates a complex mixture of airborne toxicants that includes elevated concentrations of particulate mat- ter (PM), ultrafine particles (UFPs) from diesel engine exhaust (DEE), silica, as well as volatile organic com- pounds (VOCs) and polyaromatic hydrocarbons from geological, surface and anthropogenic sources. The to- tality of materials that the individuals are exposed to is alarming to federal, state and local governmental organ- izations. Indeed, communities that are proximal to unconventional natural gas development (UNGD) well sites have greater health effects compared to communities without UNGD. However, what is not known is how ac- tive UNGD precipitates these health effects. PM, specifically fine PM (<2.5 µm in diameter, PM2.5) is a known cardiovascular toxicant. Several studies have demonstrated a significant impairment in vascular, and micro- vascular function. Combined, these studies indicate significant cardiovascular health effects even at low ambi- ent levels. Moreover, we have shown cardiac mitochondrial impairment, a significant contributor to progression of heart failure, following ambient PM exposure. However, what is not known is the relative toxicity of specific sources (source apportionment) or the mechanisms of cardiovascular injury following pulmonary PM2.5 expo- sure. The long-term goal is to establish physiologic mechanisms that explain the epidemiological health pat- terns during UNGD. The objective for this R15 application is to substantially advance the scientific understand- ing of the mechanisms that link pulmonary UNGD PM2.5 to remote tissue dysfunction. The central hypothesis is that pulmonary exposure to PM2.5 collected on-site during hydraulic fracturing will have greater microvascular and mitochondrial dysfunction, characterized by disturbances in mechanisms supporting normal arteriolar con- striction, endothelium-dependent dilation, mitochondrial function, and pro-apoptotic protein expression leading to cardiac functional declines. This hypothesis will be tested by 1) identifying the mechanistic alterations in mi- crovascular and mitochondrial function during different stages of UNGD, 2) identifying the cardiac functional declines that result from microvascular and mitochondrial dysfunction. The rationale for this work is that pro- posed research will add substantially to the mechanistic insights of PM2.5-induced microvascular and mito- chondrial dysfunction, while supporting our mission to educate and prepare students. Utilizing students to test theses aims will allow the students to gain knowledge in microscopy, necropsy, anatomy, biochemistry, and microvascular and cardiovascular physiology. The research proposed is innovative because it directly deter- mines toxicity of the complete matrix of toxicants produced during three phases of UNGD. The proposed re- search is significant as it will assess cardiovascular toxicity during different phases of drilling as well as mech- anisms of dysfunction that will bridge the gap between basic science and epidemiological UNGD health effects.
Science Code(s)/Area of Science(s) Primary: 69 - Respiratory
Publications See publications associated with this Grant.
Program Officer Srikanth Nadadur
to Top