$7.5 Million Grant Establishes Toxicogenomics Center

Duke University and four other U.S. academic medical centers were awarded more than $37 million to unravel the interplay between genes and the environment to better understand why some people develop disease and why some remain unaffected when exposed to the same environmental factors.

The five-year grant from the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health (NIH), creates the National Toxicogenomics Research Consortium. Researchers from the Duke University Medical Center and the Nicholas School of the Environment at Duke will receive $7.5 million.

This project represents one of the first large NIH-funded projects in Duke’s Institute for Genomics Sciences and Policy (IGSP).

The other participating centers in the consortium are Fred Hutchinson Cancer Research Center, Seattle; Massachusetts Institute of Technology, Cambridge, Mass.; University of North Carolina-Chapel Hill; and Oregon Health and Science University, Portland. The NIEHS will coordinate the consortium’s activities from its Research Triangle Park, N.C., headquarters.

Dr. David Schwartz, chief of pulmonary medicine at Duke and principal investigator for the Duke effort, said that a number of specific Duke projects will focus on asthma, pulmonary fibrosis neurodevelopmental aspects of disease, as well as the effects of exposure to different metals on health.

“Even in simple genetic disorders there is wide variation in the severity of disease,” Schwartz said. “Genetics is only a part of the complex issue of disease development. We want to understand more about how different outside factors interact with genes in determining how, or if, a particular disease occurs.”

The researchers plan to subject well-known animal models of disease — such as mice, zebrafish and worms — to such known environmental stressors as bacterial infection, malnutrition and exposure to metals.

Using an approach called gene expression profiling, the researchers can screen thousands of genes at a time to detect subtle genetic differences between models that appear unaffected by a particular environmental stress and those that succumb to disease.

As candidate genes are identified in animal models, the corresponding genes in humans will be tested to see if the environmental stressors have the same effect. If the gene in question does appear to play a role in disease, Schwartz explained, new therapies can be targeted to that gene.

“By the end of five years, we hope to be able to use this approach to discover new proteins that can be of importance in the development of human disease,” Schwartz explained. “These discoveries can lead to new targets for potential drugs, or it can help us identify particular susceptible individuals who might be at a higher risk for disease.”

This marks the third recently established genomics project under the umbrella of the IGSP ? other scientific projects are investigating the role of genetics in cardiology and brain cancer.

“This grant represents one of the key milestones in moving the IGSP forward,” said geneticist Joseph Nevins, a Howard Hughes Medical Institute investigator at Duke and interim director of the Center for Genome Technology, one of five research centers that are part of the IGSP. “With the unique medical and environmental expertise available here at Duke, we can take advantage of the genomics infrastructure to better understand how genes and environmental agents interact to affect the whole organism.”

The IGSP, established in 2000 with $200 million in institutional funds, represents Duke University’s comprehensive response to the broad challenges of the genomic revolution. IGSP activities are organized through five research centers: the Center for Genome Technology, the Center for Human Genetics, the Center for Human Disease Models, the Center for Bioinformatics and Computational Biology and the Center for Genome Ethics, Law and Policy.