October 17, 2008

Marnett’s contributions to chemical toxicology honored

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Lawrence Marnett, Ph.D.

Marnett’s contributions to chemical toxicology honored

Lawrence Marnett, Ph.D., professor of Biochemistry, Chemistry and Pharmacology, has received the first Founders' Award from the American Chemical Society's Division of Chemical Toxicology.

The award recognizes Marnett's contributions to the field of chemical toxicology, “in which he has been a pioneer and unifying force,” the division said in a statement. Marnett received the award during the fall ACS meeting.

“I'm very pleased to win the Founders' Award, especially since it's the first time it has been given,” Marnett said. “The award recognizes the contributions that many individuals in my laboratory have made to our research program as well as productive collaborations with multiple colleagues at Vanderbilt. It is a great honor.”

Marnett has focused on “endogenous carcinogenesis” — how molecules produced by the body, particularly during inflammation, damage DNA and cause cancer. His team's efforts have centered on a small molecule called malondialdehyde, a metabolite of the cell membrane lipid arachidonic acid.

Marnett and his group have identified all of the products formed when malondialdehyde reacts with DNA. They have studied the biological activity of these “DNA adducts” — whether they cause mutations, how effectively they cause mutations, and how they are repaired. The group has also developed methodology to detect the presence of malondialdehyde-DNA adducts in people, publishing the first report of this type of DNA damage in the journal Science in 1994.

A number of groups have since demonstrated the presence of DNA adducts formed from other endogenous compounds.

“There's DNA damage going on all the time — some from environmental chemicals, some from endogenous chemicals,” Marnett said. “The real challenge to the field is to discover how those things interact to push a cell over the limit and cause mutations in critical genes.”

Marnett and his colleagues have also explored how the cyclooxgenase (COX) enzymes work. The group is using structure-based approaches and medicinal chemistry to design selective COX-2 inhibitors as potential therapeutics for inflammation and cancer prevention.

Marnett is the founding and current editor of the ACS journal Chemical Research in Toxicology, which just celebrated its 20th year. He was also one of the founders of the ACS Division of Chemical Toxicology.

After earning his Ph.D. in Chemistry from Duke University, where he worked with Ned Porter, Ph.D., Marnett completed postdoctoral training with Nobel laureate Bengt Samuelsson, M.D., at the Karolinska Institute in Sweden. Marnett was a professor of Chemistry at Wayne State University for 14 years before joining the Vanderbilt faculty in 1989.

He is the director of the Vanderbilt Institute for Chemical Biology and the Mary Geddes Stahlman Professor of Cancer Research.