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Dr. Paul R.G. Cunningham
Doug Boyd
Crystal Baity
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Karen Shugart
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Emerging Research

Dr. Jared Brown's prestigious award aids study of nanomaterials

By Karen Shugart

It was in graduate school that Dr. Jared Brown, above, began the work that would just six years later net him and his colleagues more than $3 million for research.

First came a $75,000 grant from the N.C. Biotechnology Center in June. That same month, Brown, an assistant professor of pharmacology and toxicology at the Brody School of Medicine, learned officially he received a $2.2 million grant as one of a half-dozen researchers to be awarded an Outstanding New Environmental Scientist Award.

Awarded to early-career scientists, the National Institute of Environmental Health Sciences' program since 2006 has annually identified and supported scientists who intend to dedicate their careers to environmental science research.

Then, in early September, Brown learned that he and Dr. Christopher Wingard, associate professor of physiology, will share in a $3.75 million, five-year, multi-project grant funded by the National Institutes of Health. Brown and Wingard will each lead $700,000 projects.

It's a slate of accomplishments that's not too shabby for someone just six years out of graduate school. Even more impressive, perhaps, is the area of his research — carbon nanotubes and the nascent study of nanomaterials' effects on the human body.

Smaller than 1/1000th of a millimeter, carbon nanotubes are tube-shaped fibers that have proved useful in products as varied as cosmetics, sunscreens, bicycle frames, electronics, sailboats, space shuttles and pills. They've even been used to clean up oil spills.

"This is probably one of the most rapidly growing commercial applications of material science," said Wingard. "There's more than 800 registered nanomaterials out there in commercial use."

Until recent years, however, their effects on human health have gone largely unexamined and unregulated. Now, agencies including the NIH, the Environmental Protection Agency and the National Institute for Occupational Safety and Health are pushing for answers.

"Are these things toxic and, if they are, what levels are we exposed to? And if we are exposed, what level is safe, and what level is not safe?" said Brown, citing some of scientists' questions.

There's reason to be asking questions. Experiments have shown that rodents, when exposed to nanotubes in the lungs, developed pulmonary inflammation and fibrosis, Brown said.

"What's not known is how that might occur," he said.

Brown and Wingard aren't alone among ECU researchers in asking such questions. Others examining nanotechnology's effects on the human body include Dr. Alexander Murashov, associate professor of physiology; Dr. Wayne Cascio, director of research at the East Carolina Heart Institute; and Dr. Dave Brown, assistant professor of physiology.

For his part, Jared Brown has studied how response to nanotubes is affected by mast cells, which play an important role in allergic reactions. He's studied two groups of mice, one with the cells and one without, and found that the mice with mast cells developed pulmonary inflammation and fibrosis when exposed to nanotubes. The ones lacking the cells did not.

"It was a completely different response, almost like night-and-day," Brown said.

Brown suspects that nanotubes damage the lung through the epithelium or through a macrophage. Those cells, he hypothesized, release interleukin 33, a protein that acts as a signaler between immune system cells, which in turn activates the mast cell.

If mast cells provide key answers to understanding the body's response to certain nanotubes, then perhaps scientists have a leg up already on preventing adverse effects, Brown said. An array of drugs targeting mast cells or mast cell products such as antihistamines is available that address allergic reactions.

Studying the effects of nanomaterials such as carbon nanotubes is complicated by the abundance of types available. With already more than 800 nanomaterials registered and many more in development for commercial use, there are a lot of unknown effects, Wingard said.

Brown said probably 20 to 30 U.S. companies make their own nanotubes.

"How they're made can vary from lab to lab to company to company, so even if you compared a carbon nanotube from one company to another, you're going to get different biological responses," he said. "So there's this big push to try to identify common mechanisms to model and predict effects."

The ONES Award, much like the Biotechnology Center grant, will help Brown identify properties that might make carbon nanotubes toxic.

The most recent grant, which Brown will share with Wingard as well as researchers from RTI International and the Hamner Institute, will create a Center for Estimating Human Health Risks from Exposure to Nanomaterials. Brown's project in the joint effort will examine the uptake of nanomaterials by epithelial and endothelial cells in rodents.

Their conclusions will contribute a growing body of research that may have important ramifications for nanotechnology: Will the rapidly growing industry need regulation? Should rules be put in place to protect workers in the industry — or members of the public — from some exposure to carbon nanotubes, just as laws were passed to regulate asbestos, another long, thin fiber?

"The idea is to try to pre-empt something like the asbestos fiasco," Brown said.