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Mining Science for Better Health Outcomes

The College of Pharmacy’s Department of Pharmaceutical Sciences has long been involved in research related to toxicology and environmental health. Its work has coalesced in the last few years to a focus on environmental metals.

Department faculty are in a prime spot to study the health effects of environmental contamination from uranium left behind after decades of mining on Indian lands and of arsenic, a naturally occurring metalloid that contaminates well water across New Mexico.

The METALS group (Metal Exposure and Toxicity Assessment on Tribal Lands of the Southwest) brings together basic science researchers and toxicologists to better understand how metals cause disease, a critical step in preventing further exposures and affecting environmental policies.

The college has also just won $5 million in funding from the National Institute for Environmental Health Sciences, the National Institute for Minority Health and Health Disparities and the U.S. Environmental Protection Agency to form the Center for Native American Environmental Health Equity Research. It is also developing a Superfund Basic Science Research Center to study these questions and reduce risks.

College of Pharmacy Colleagues Collaborate on Environmental Research

“We see this as a emerging program that really brings together a lot of the skills and expertise within the college,” said Johnnye Lewis, a research professor of pharmaceutical sciences. “It’s really a chance to merge a lot of research interests that previously were not collaborating. And as a team we’re stronger than we were as individuals.”

Lewis’s focus on the legacy of uranium mining on the Navajo reservation began 15 years ago when some Navajo communities asked for help in determining whether exposure to uranium through unregulated drinking water was leading to kidney disease. At the time, their population had the highest rates of kidney disease and the earliest onset in the country.

Following a uranium-mining boom that ended in the 1980s, 1,100 sites associated with 500 abandoned mines remain as sources of environmental pollution. In the western United States, there are more than 10,000 waste sites associated with more than 4,000 abandoned uranium mines.

Lewis’s survey data on the Navajo reservation revealed a link between direct exposure to uranium and wastes during the period of active mining and kidney disease. For those who continue to have chronic, lower-level exposure to the waste that remains abandoned today, the link to kidney disease wasn’t there, but those people were at a higher risk for cardiovascular and autoimmune disease and immune system dysfunction.

It is not only uranium that remains in water and soil after the mining companies leave. Vanadium, arsenic, copper, nickel and other metals are also found at the sites.

“With hundreds of thousands of abandoned hardrock mines, we need to know how these mixtures affect this population,” Lewis said.

Finding that out has led into the science laboratories within the College of Pharmacy. Laurie Hudson, a professor in the college’s Department of Pharmaceutical Sciences, had a longstanding interest in toxicity and cancer. Jim Liu, the college’s associate dean for research, had a complimentary interest in oxidative stress. Together the two started working on a very basic science question related to the METALS team’s work: How does arsenic cause problems in cells?

They found that arsenic inhibited the ability of cells to repair DNA, an important function for health. And they found that arsenic interacted with or could bind to some DNA repair proteins that were controlled by a particular structure called a zinc finger.

“If arsenic is kicking zinc out from important proteins,” Hudson said they reasoned, “maybe you can overcome that. If you change the balance of zinc and arsenic, maybe it could be protective.”

They tried shifting the balance between arsenic and zinc in cells and mice and found that raising the zinc level could offset the effect of arsenic.

Hudson and Liu just received a grant to look at low zinc levels as a risk factor in terms of arsenic-induced damage.

They will be examining blood taken from women in another of Lewis’s projects, the Navajo Birth Cohort Study. That study has recruited 500 Navajo women who are expecting babies and 200 of their spouses to obtain health information at a prenatal stage and after giving birth. They will be followed for at least a year.

For Liu and Hudson, studying how zinc from prenatal vitamins affects DNA damage in arsenic-exposed pregnant women will open a door on further research into how adequate zinc levels may protect against disease.

“It was a natural partnership in asking whether having sufficient amounts of zinc would be protective of people,” Hudson said. “Looking at women taking zinc supplements we will be able to see whether there is a protective effect.”

If zinc is protective, it would be a low-cost way to prevent some DNA damage associated with arsenic exposure.

Another colleague in the Department of Pharmaceutics, Matthew Campen, is looking at the problem from another angle. He is interested in the cardiovascular effects of air pollution.

Using blood samples from the Navajo birth project, Campen and graduate student Molly Harmon are looking for biomarkers of inflammation related to cardiovascular disease.

Plotting where the Navajo participants live in relation to abandoned mine sites, Campen’s laboratory found a strong correlation.

“It shows the closer you live to these abandoned uranium mines, the greater your overall inflammatory potential is,” Campen said. “It’s very preliminary, but it’s just flooring me what a strong relationship it is.”

Inflammation is associated with cognitive, autoimmune, metabolic and cardiovascular disease, so the findings could lead to further inquiry into the association between uranium and those diseases.

 The collaboration between scientists within the College of Pharmacy led to that discovery, and Campen is excited about even more collaboration with the newly funded center.

“It dramatically increases our abilities to do research and interact with the communities that are affected by the mining sites that have been abandoned,” he said. “It puts us at the top of the country for environmental health research on these questions.”

 Another line of inquiry asks about how arsenic and uranium cause disease in different populations.

Scott Burchiel, a senior associate dean at the College of Pharmacy and its former associate dean for research, received the first National Institutes of Health grant at the college and has been continually funded by NIH for a quarter of a century.

His focus has always been on environmental health and toxicity. “My particular passion is immunotoxicology,” Burchiel says. “The toxicity to the immune system. My new passion right now is arsenic exposures.”

While his research is focused right now on clinical studies involving people in Bangladesh who have high arsenic levels, Burchiel’s research has applications close to home. “Some of the exposures here in New Mexico,” he says, “are as high as they are in Bangladesh.”

In laboratory tests looking at the effects of arsenic and uranium on the immune system, Burchiel is determining whether exposure during pregnancy is associated with greater risk.

“If you expose pregnant mice to arsenic, they’re much more sensitive,” Burchiel found. “So we’re starting to do a major new effort on gestational exposures of arsenic and uranium in mice.” This will be relevant for the Navajo birth cohort as well.

Burchiel is also looking at genetic differences between people – the so-called “gene and environment interactions” ­– in terms of arsenic and uranium exposure.

“Depending on genetic makeup,” he says, “you may be more or less sensitive to arsenic and uranium exposure. It may be the way you metabolize it, the way you clear it. Who knows? We’re trying to define that.”

All of this research together aims to give health providers a better understanding of how to treat patients with disease and hopefully preventing disease and give policy makers a better road map for how to spend resources to clean up mine sites.

“We want to make sure the science is driving policy change to reduce risk and to provide better health care,” Lewis said.