FROM THE VICE PRESIDENT
Sidebar: Are oceans becoming acidic?
LOST LEWIS AND CLARK
Sidebar: Neurons get their close-up
Sidebar: Core facility models molecules
A HAZARDOUS WORLD
Sidebar: Genes, the environment and you
Cover: An illustration of UM's Main Hall tower bathed in the glow of a fictitious smoldering Earth.
Vision is published annually by The University of Montana Office of the Vice President for Research and Development and University Relations. It is printed by UM Printing & Graphic Services.
PUBLISHER: Daniel J. Dwyer. MANAGING EDITOR AND GRAPHIC DESIGNER: Cary Shimek. PHOTOGRAPHER: Todd Goodrich. CONTRIBUTING EDITORS: Brianne Burrowes, Brenda Day, Judy Fredenberg, Joan Melcher, Rita Munzenrider, Patia Stephens and Alex Strickland. WEB DESIGN: Patia Stephens. EDITORIAL OFFICE: University Relations, Brantly Hall 330, Missoula, MT 59812, 406-243-5914. MANAGEMENT: Judy Fredenberg, Office of the Vice President for Research and Development, 116 Main Hall, Missoula, MT 59812, 406-243-6670.
a Hazardous World
Center studies environmental impacts on human health
By Cary Shimek
When director Andrij Holian, an expert on environmental health hazards and chronic lung diseases, first considered moving to Montana from a prestigious position at the University of Texas Houston Health Sciences Center, his colleagues told him he was crazy.
Why would he leave one of the most polluted urban areas in the nation for the perceived cleanliness of Big Sky Country? Houston was where the action was.
While considering his options, Holian got a call from U.S. Sen. Max Baucus. Montana’s senior senator said the full scale of asbestos contamination in the former mining town of Libby was becoming clear, and he wanted UM’s new Center for Environmental Health Sciences to be led by someone like Holian, who had previous experience working with asbestos-related diseases.
That tipped the scales for the scientist, who headed north in 2000 to help found one of the few environmental health science centers in the Pacific Northwest.
CEHS works to advance knowledge of environmental impacts on human health. The center studies a wide range of issues, such as the mechanisms of disease linked to Montana’s mining legacy, as well as the pollution dangers mountain dwellers face from wood smoke, forest fires and polluted air trapped in the valleys by winter inversions.
“What I’ve tried to do is assemble the variety of investigators necessary to address some of these issues,” Holian says. “I think we can do an amazing amount of good by developing some early markers for the diseases we study. I hope some of the things we discover will eventually lead to some new industries or new technologies — if not cures, at least earlier diagnoses so that people can be treated better.”
Holian leveraged Environmental Protection Agency funding, as well as resources from the National Science Foundation’s Experimental Program to Stimulate Competitive Research, Health and Human Services, and the Centers for Disease Control, to grow CEHS into a robust Center for Biomedical Research Excellence (COBRE).
The center has earned two five-year COBRE grants, both in excess of $10 million, from the National Institutes of Health. Besides COBRE funding, by 2007 CEHS investigators had pulled in another $20 million in research dollars from various sources.
Holian says the center now includes 16 faculty members and six faculty affiliates in UM’s College of Health Professions and Biomedical Sciences, chemistry and computer science departments, and the Division of Biological Sciences. He says the center is designed to facilitate interdisciplinary research.
“Problems are so big that it’s difficult in modern science for the individual investigator,” he says, adding that the more interdisciplinary the approach is, the better the projects tend to be accepted by funding agencies.
“We now employ upwards of 60 people,” he says, “ranging from faculty, postdoctoral fellows, graduate students, technicians and, importantly, undergraduates, who gain experience in biomedical research. During summers we also hire high school students.”
The center also employs a wide variety of world-class research techniques in its labs, such as microarray fabrication, proteomics, molecular histology and fluorescence cytometry.
Holian says CEHS researchers had a hand in designing the 2007 addition to the Skaggs Building, with its more open layout for laboratories to encourage investigator interaction and exchange of scientific ideas. They also advocated for the science-education learning center for public schoolchildren and to promote adult education.
Western Montana provides a fertile landscape for CEHS research. Decades of vermiculite mining in Libby have afflicted hundreds of people with asbestos-related diseases. A massive mining Superfund site stretches downstream from Butte to Milltown, where elevated arsenic levels are found. Many area streams and fish contain mercury, and the small town of Superior is surrounded by lead and arsenic mine waste. In addition, a wintertime trick of the state’s geography traps fumes from biomass burning and fossil fuels in the valleys with people.
Sidebar: Genes, the environment and you
Holian himself studies lung respiratory ailments — his own son has asthma — as well as lung fibrosis, the scarring that can be triggered by jagged asbestos fibers, silicates and other airborne particulates. He says lung inflammation appears to trigger many diseases, and his work tries to unravel this process at the molecular level.
Holian says scar tissue can resolve — fade — over time if the underlying inflammation can be cured. He says high amounts of a protein called IL-13 have been shown to produce fibrosis in mice, and if a target cell stops producing that protein, the scarring retreats. Can the same happen with people?
Among the center researchers doing exciting work is Associate Professor Howard Beall, who, along with Associate Professor Doug Coffin, found that arsenic exposure is a risk factor for cardiovascular disease. In a mouse model, arsenic caused a significant increase in atherosclerosis, the hardening of arteries because of plaque buildup.
more recent work shows that the increase also is significant at 10
Beall, who also studies anticancer agents, says his lab now works to understand the basic mechanisms of how arsenic affects the cells lining the inside of arteries to cause atherosclerosis.
Many talented CEHS scientists wouldn’t be in Montana without the center. Among them is Associate Professor Fernando Cardozo-Pelaez, originally from Colombia. He studies Parkinson’s disease — especially how DNA damage leads to the disease and the mechanisms that allow neurons to repair themselves.
“With Parkinson’s there is a specific circuit in the brain that is lost called the nigrostriatal pathway,” Cardozo says. “The problem is that we do not know in the majority of cases why the neurons are lost. If we can understand that mechanism, we may identify new points for intervention.”
He says people in rural areas are more likely to develop Parkinson’s, perhaps because of pesticide use, drinking well water or heavy metals exposure. Manganese is one metal that has been shown to promote the disease, so Cardozo’s team uses specially engineered mice — they lack a DNA repair system — as a model to study Parkinson’s and manganese toxicity.
Neurons are among the only cells in the body that can’t divide and replenish themselves, and Cardozo’s group is experimenting with using viruses to express an enzyme that protects neurons.
“So if you have a population that lacks DNA repair,” he says, “hypothetically you could try to replenish that deficiency by putting the enzyme back by gene therapy.”
Assistant Professor Jean Pfau studies silica or asbestos exposures and their effects on human immune systems. Her work suggests that people exposed to asbestos in Libby may be more prone to autoimmune diseases such as lupus or rheumatoid arthritis.
Each autoimmune disease produces a unique pattern of antibodies that can act like a signature to scientists. “So we are trying to figure out what the signature is for asbestos-induced autoantibodies,” Pfau says.
Her lab also studies structural fibroblast cells in lungs — the ones that get activated to produce excess scar tissue. Some of her data suggests autoantibodies may bind to fibroblasts, activating them to produce collagen. If this is the case, the natural autoimmune response helps drive fibrosis, increasing lung scarring.
Another faculty member doing intriguing work is Assistant Professor Curtis Noonan. As an epidemiologist, he studies the distribution of disease among human populations. He was recruited to UM in 2004 from the Centers for Disease Control and Prevention in Atlanta.
Noonan now examines wood-smoke air pollution. In Libby, a community that historically exceeds the EPA’s air quality standards during winter air inversions, a massive change-out program replaced most old woodstoves with EPA-certified wood or pellet stoves in an effort to reduce pollution.
Noonan’s collaborator, Research Assistant Professor Tony Ward, did a source-apportionment study to determine the particulate matter in Libby air. It turned out 82 percent was from wood smoke.
“We are concerned about the impacts on public health,” Noonan says, “so we are tracking changes in respiratory infections and school absences among children up there. We also track the outside and indoor air quality in schools and homes.”
The study is ongoing, but preliminary findings show particulate levels in Libby’s ambient air have gone down since the change-out program began.
Another research interest of Noonan and Ward is learning whether wood smoke-derived particulate matter is less harmful than urban, industrial sources. This answer could have major implications for mountain communities struggling to meet EPA standards during winter inversion events.
With all the nasty environmental problems CEHS scientists study, one might wonder whether it’s even safe to live in Montana. Perhaps Pfau summed up the group’s sentiments best:
“Montana is as safe as any place, but the world presents a lot of challenges. I’m really glad we are looking into these exposures so we can watch our world, improve the way we handle our world and watch out for our own health.”
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