December 15, 2006

Proteomics at heart of new center

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Lawrence Marnett, Ph.D., will direct the newly established NFCR Center for Proteomics and Drug Action at Vanderbilt.
Photo by Susan Urmy

Proteomics at heart of new center

Vanderbilt University Medical Center has received a five-year, $1 million grant from the National Foundation for Cancer Research (NFCR) to apply the powerful science of proteomics to drug discovery.

The grant, announced Tuesday, will establish the NFCR Center for Proteomics and Drug Action, to be directed by Lawrence Marnett, Ph.D.

Other principal investigators are Richard Caprioli, Ph.D., and Daniel Liebler, Ph.D.

“You have got what I believe is the world’s best proteomics faculty,” NFCR president Franklin Salisbury Jr., said during a dedication ceremony at Vanderbilt on Tuesday. “This (center) is unlike anything else in the world, and it’s going to really make a difference.”

Proteomics is the study of proteins and how they work. One method for studying proteins, called “molecular fingerprinting,” attempts to identify patterns of proteins in the blood and tissues that can be used to detect diseases like cancer earlier and monitor therapy better than is now possible.

Another technique, high-throughput screening, allows researchers to rapidly test thousands of small molecules for their ability to activate receptor proteins involved in a wide range of physiological functions. The aim is to improve the yield of new drugs for disorders as diverse as malaria and Parkinson's disease.

The Vanderbilt center joins nine other NFCR-funded “research discovery centers” that are pursuing advances in understanding, diagnosing and treating cancer.

Marnett, whose research has been supported by the Bethesda, Md.-based foundation for several years, directs the Vanderbilt Institute of Chemical Biology and the A.B. Hancock Jr. Memorial Laboratory for Cancer Research. He studies how — from a chemical point of view — drugs exert their effects.

Liebler, who directs the Proteomics Laboratory and the Jim Ayers Institute for Pre-Cancer Detection and Diagnosis, studies how small molecules or drugs interact with their target proteins, and looks for proteins that could be used as “biomarkers” for monitoring disease or drug effects.

Caprioli, who directs the Mass Spectrometry Research Center, is pioneering techniques such as imaging mass spectrometry to study the location and movement of proteins that are potential drug targets or biomarkers for disease.

While the three scientists are affiliated with the Vanderbilt-Ingram Cancer Center, Marnett said the techniques they develop will be “fundamental” and not limited to cancer.

Advances in genomics, proteomics and chemical biology at Vanderbilt and elsewhere have led to the identification of many new, biologically active molecules. In order to develop them as potential drugs, however, scientists must determine exactly how these molecules act in the body.

“You just can't bring things forward anymore if people don't understand the mechanism,” Marnett explained. “We're going to use … the sizeable investment in proteomics here at Vanderbilt to develop technologies that help us identify those molecular targets.”

Drug development also requires the identification of biomarkers of efficacy and toxicity — early indicators that a potential drug is working or that it is causing adverse effects. “Anything that we generate (in this area) would have real impact,” he said.

Marnett said the new center will complement the Jim Ayers Institute, which is harnessing molecular fingerprinting techniques to improve detection of “pre-cancer,” with an initial emphasis on colorectal cancer.

The center, launched at Vanderbilt-Ingram last year with a gift from West Tennessee businessman Jim Ayers, also is developing technologies to allow earlier cancer diagnoses and to predict tumor response to treatment so that the most effective therapy can be selected.

The National Foundation for Cancer Research was founded in 1973 by Washington, D.C., attorney and entrepreneur Franklin Cary Salisbury and his wife, Tamara, a research chemist who worked for the National Cancer Institute and Office of Naval Research.

Initially inspired by the work of Nobel laureate Albert Szent-Györgyi, one of the first scientists to explore the connections between free radicals and cancer, the foundation currently supports a wide range of research “relating to the prevention, early diagnosis, better treatments and, ultimately, a cure for cancer.”

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Marnett is the Mary Geddes Stahlman Professor of Cancer Research and professor of Biochemistry and Chemistry. Caprioli is the Stanley Cohen Professor of Biochemistry and professor of Pharmacology and Chemistry. Liebler is professor of Biochemistry and Pharmacology.