U-M to study why childhood exposure to toxicants makes us sick as adults

May 10, 2011
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ANN ARBOR—A newly funded center at the University of Michigan will allow researchers from the School of Public Health and the Medical School to study the way environmental toxicants change genetic programming, and how those changes contribute to chronic disease in adults.

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The center, a collaboration between the U-M SPH and the U-M Health System, is the first of its kind at U-M and is the only new National Institutes of Environmental Health Sciences P30 Core Center to be funded (as opposed to renewals of existing centers) in the last six years, said the center’s director, Dr. Howard Hu.

Hu said the landmark grant of $4 million was his top research goal when he came to U-M as chair of the Department of Environmental Health Sciences in 2006.

“These grants essentially provide money for new pilot projects, for enhancing the labs that do the research, for young scientists, and for outreach,” said Hu, who helped direct a similar P30 Core Center at Harvard for six years. “They help universities with a critical mass of environmental health sciences to reach the next level of productivity.”

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Dr. Bruce Richardson, professor of internal medicine at the U-M Medical School, is co-director.

“The University of Michigan P30 Core Center will facilitate collaborations between investigators in the School of Public Health and the U-M Health System, capitalizing on the strengths and resources of both schools as well as the expertise of their faculty,” said Richardson, also chief of the Rheumatology Division at the Ann Arbor Veteran Affairs Hospital. “Together, the scientists and clinicians will investigate how agents in the environment modify gene expression to cause diseases throughout life, using state-of-the-art-technology and groundbreaking concepts in epigenetics.”

The center will have three research teams focused on epigenetic regulation, oxidative stress, and endocrine disruptors. They’ll initially target four conditions: asthma; prematurity; metabolic syndrome; and neurodegenerative disease.

A good example of an area researchers hope to better understand is the link between pollution, inflammation and cardiovascular disease, Hu said. “We now know that oxidation and inflammation are major risk factors for heart attack and cardiovascular disease, but we don’t know how air pollution makes those things happen,” Hu said. “If we’re successful, we can better pinpoint what components of air pollution drive this, and hopefully generate better data for regulating air pollution as well as new potential targets for drug therapy.”

Epigenetic changes are suspected to be a major mechanism for early life exposures that increase the risk of cancer, Alzheimer’s, and other chronic diseases. Take Alzheimer’s, a disease that in repeated twin studies often afflicts only one twin. This clearly demonstrates that it’s not just a genetic disease or both twins would have Alzheimer’s, Hu said. In fact, it’s suspected that genetics contributes to less than 50 percent of the condition’s occurrence.

Hu and several colleagues involved in the P30 are also receiving a $450,000 grant from the University Research Corridor to collaborate with Wayne State and Michigan State universities to build off the P30 Core Center by using the Michigan Biorepository, the archive of blood spots for all Michigan children born since 1984.

Researchers can use blood spots to retroactively determine exposures and epigenetic patterns and relate that to current health outcomes among those individuals. In this way, researchers can look at epigenetics in humans, and Hu said one area they’ll study is autism. Right now in children with autism it’s very difficult to trace exposures during a mother’s pregnancy or the child’s early life, so it’s very difficult to collar environmental suspects.

“With this new URC grant, we can access blood spots of children who currently have autism,” Hu said. “They are useful in determining what exposures occurred during pregnancy and what’s changed in the epigenome and later in life.”