Many of us face safety risks at work, but those serving in the military or working in law enforcement and industrial settings are at greater risk for dangerous chemical exposures. This risk is significant, as nearly 10% of occupational illnesses or injuries that lead to death are caused by exposure to chemicals.

Jonathan Boyd—a West Virginia University School of Medicine researcher—is investigating the inflammatory responses produced by exposure to chemical agents. The Defense Threat Reduction Agency recently awarded him over $2 million for the project.

“I’ve been working on understanding inflammation in both humans and animals for a long time,” said Boyd, a professor in the Department of Orthopaedics. “We have basically created an encyclopedia of inflammogens from different causes—not only what the causes are, but also what the inflammation looks like from a biochemical standpoint. I thought that now would be a good time to compare different chemical exposures.”

Inflammation is our body’s way of fighting off things that can harm it. When our cells encounter inflammogens, such as toxins or an injury, they release chemical signals that trigger an inflammatory response from the immune system.

Boyd and his team have previously studied the response to several different types of inflammogens, including traumatic injury, infection and even social interaction. In this new study, the team is exploring the response to chemical exposures at both the whole-body and tissue levels.

For the study, whole-body imaging for toxicity will be developed to map where and when local inflammatory responses happen in various tissues of animal models. The team will then isolate these tissues and study their genes, proteins and metabolites to learn exactly what inflammatory markers the tissues are producing.

Boyd seeks to compare and contrast the inflammatory responses to five different agents by determining what inflammatory markers the compounds share and which ones are unique. Understanding the markers produced for all exposures could lead to the development of a common treatment for chemical exposures. On the other hand, knowing which markers are distinct could help clinicians determine the chemical responsible for victims of toxic exposures.

“We are investigating inflammation markers, or biomarkers of inflammation, across different compounds,” Boyd said. “We’re looking for both universal markers that we could use for potential development of therapeutics and disparate biomarkers of inflammation that we can use for differential diagnosis.”

Besides this main goal, the project aims to compare how different tissues change their shape, structure and function when chemical agents induce inflammation. This is a new field that Boyd is pioneering, one that he calls “Toximaging.”

“Toximaging will allow us to noninvasively examine all types of exposures that may lead to toxicity,” he said. “This will enable us to diagnose both target organs and tissue response times as they occur.”

This project is a collaboration with the Medical Readiness Systems Biology branch of the Walter Reed Army Institute of Research and the U.S. Army Combat Capabilities Development Command Chemical Biological Center.

To make this collaboration possible, Boyd will travel to WRAIR and CCDC to teach researchers there how to perform the imaging and biochemical analysis that he and his team do at WVU.

“We’re transferring the knowledge that we have gained and techniques that we have developed to these federal laboratories, which enhances the reputation of the university and the state of West Virginia,” he said.

Imaging results will also be easily translatable as some of the techniques the team will use on animal models can be approved for patients in the clinic.

“Absolutely we want to translate this into humans,” Boyd said. “We want to go right back to humans afterward to understand localized inflammation and the impacts of it in people.” o

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