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September 9, 2002

Doetsch project studies cellular responses to stress

By Vince Dollard

Five Emory and Winship Cancer Institute (WCI) investigators will collaborate on a series of studies that could have direct relevance to our understanding of how cancer develops in humans.

The project, “Cellular Responses to Genotoxic Stress,” is funded by The National Institute of Environmental Health Sciences (NIEHS) and is made up of five separate but collaborative research initiatives, each investigating a different aspect of DNA repair, damage tolerance and damage prevention in response to exposures to radiation or chemical agents that can corrupt cellular DNA. NIEHS is funding the collaboration for $1.2 million for 2002–03 and will support this project each year at a similar level for a total of five years.

“The genetic material of all organisms is subject to a daily barrage of physical and chemical insults coming from the environment or produced by normal cellular metabolism,” said Paul Doetsch, professor of biochemistry and radiation oncology and WCI interim associate director for laboratory research. “These genotoxins can change the chemical structure of DNA components and its coding properties, which can set the stage for various biological consequences, including cell death, cell mutation and—in the case of humans—the development of cancer.”

The project will employ yeast and bacterial model systems to study strategies used by organisms to resist the introduction and effects of DNA damage, including DNA repair, damage tolerance and direct prevention pathways. Previous work has demonstrated that these pathways are similar in most species, including humans. Therefore the studies are expected to contribute to scientists’ understanding of how cancerous cells develop in humans.

“We intend to characterize the interacting and complementary networks of systems that operate at different levels during exposure to DNA-damaging events,” said Doetsch, principal investigator for the entire project.

In addition to Doetsch, the four Emory investigators participating in this program project are Gerald Shadel, assistant professor of biochemistry; Wolfram Siede, assistant professor of radiation oncology; Bernard Weiss, professor of pathology; and Yoke Wah Kow, professor of radiation oncology.

The NIEHS is one of 25 institutes and centers of the National Institutes of Health. NIEHS seeks to reduce the burden of human illness from environmental causes by understanding how various environmental elements interrelate. The NIEHS funds and conducts multidisciplinary biomedical research programs, prevention and intervention efforts, and communication strategies that encompass training, education, technology transfer and community outreach.