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NFCR, Vanderbilt Create Center That Uses Proteomic Technologies to Study Cancer

Saying that advanced cancer research has moved beyond the genome, the nonprofit National Foundation for Cancer Research has teamed up with Vanderbilt University to launch a center focused strictly on using proteomics technologies to study the disease.
The NFCR Center for Proteomics and Drug Actions, funded with a $1 million, five-year grant from the NFCR, will join a network of eight centers established by the foundation to explore different technology platforms for cancer research. The Vanderbilt center is the only one concentrating exclusively on proteomics.
Its focus will be to use proteomic technologies to identify molecular targets for new drugs, identify new biomarkers for drug efficacy, and monitor how parent compounds of new drugs and metabolites are distributed into tissues.
The center at Vanderbilt’s campus in Nashville, Tenn., will be led by Larry Marnett, director of the Vanderbilt Institute of Chemical Biology. He will work on developing methods to make drug agents bind more tightly to their targets by manipulating the strucutre of the agents.
Additionally, Daniel Liebler, director of the proteomics lab at the Mass Spectrometry Research Center at the university, will develop techniques to covalently tag molecular targets. He also will develop biomarkers of efficacy or toxicity.
And Richard Caprioli, director of the Mass Spectrometry Research Center, will explore unbiased approaches to looking at cellular changes in proteomes induced by novel compounds.
The NFCR Center for Proteomics and Drug Actions will not be house in a new facility but instead, will be comprised of space, instruments and other resources already in existence and being used for other proteomics research at the university.
The $1 million will be used exclusively to pay graduate students and post-doc researchers to do the research. None of the money will be used to purchase instruments.
In an interview with ProteoMonitor last week, Michael Wang, vice president of science for NFCR, said that the Vanderbilt center was created in recognition of the promise that proteomics may hold in the search for a cancer cure.
In the three years since the Human Genome Project wound down, Wang said that emphasis on research has slowly moved from looking at genes to looking at the products of genes.
“Most of the new drugs currently used to treat cancer are targeted proteins, so to develop new anti-cancer drugs we really need to understand those protein targets,” he said. “Right now in [the] new-drug development industry, there is a challenge that prevents drug development: We have little knowledge about drug targets. And this center will develop new technologies, new methods [that will] allow scientists to completely understand all the targets that interact with a drug.”
Still, even with the purported promise of proteomics as a platform for cancer research and all the research in protein cancer biomarkers and proteomics-based diagnostics, material results have been lacking.
Wang blames this on a fragmented approach to the research that has too many scientists using too many different kinds of technologies and methods that make it difficult to share data.
In September, National Cancer Institute Deputy Director Anna Barker voiced similar sentiments when the institute announced the winners of five grants totaling $35.5 million over five years to test and evaluate proteomic technologies applicable to cancer research [See PM 09/28/06]. A team of researchers led by Liebler received $7.5 million under that program. The awards are part of a larger, five-year $104 million effort by the NCI to assess the use of proteomic tools and data resources for cancer research, called the Clinical Proteomic Technologies Initiative for Cancer.
One of the goals of the Vanderbilt center will be to develop technologies and methods that it hopes will become standards for proteomic-based cancer research “so that the outcomes [determined by Vanderbilt researchers] can be expanded or multiplied by other scientists,” Wang said
Additionally, the Vanderbilt team aims to study cancerous tumor tissue directly rather than relying on blood or urine samples taken from cancer patients. The tumors, he said, will give researchers more direct information about cancer.
Feeding the Kitty
NFCR’s grant comes at a time when spending by the National Institutes of Health for proteomic research has been shrinking.  Although the amount of the grant may seem modest, any financial support, especially by nonprofit organizations such as NFCR, is crucial, Marnett said.

“The thing about this type of funding that NFCR provides is that it’s unrestricted, and it gives you not only the opportunity, but the challenge to identify the most important new project and to follow up on it and get preliminary data as quickly as possible.”

“The thing about this type of funding that NFCR provides is that it’s unrestricted, and it gives you not only the opportunity, but the challenge to identify the most important new project and to follow up on it and get preliminary data as quickly as possible,” he said.
In addition to a lag time of almost a year between filing for an NIH grant and getting the funding, if it is approved, Marnett said that the NIH is looking to put the clamps on grantees whose projects have not followed their grant proposals to the letter.
“This move to increase compliance makes it, at least on paper, very difficult to do anything that’s not covered specifically in a grant. “So this kind of discovery money is going to be increasingly important,” Marnett said.
The NFCR chose Vanderbilt as the site for its proteomics-directed research center for two reasons, Wang said. First, the NFCR already had a relationship with Marnett, including funding other of his projects. Over the years, Marnett had been in discussions with NFCR about using Vanderbilt’s proteomics technologies to discover new cancer drugs. 
Second, Vanderbilt has developed a reputation as one of the leading proteomics research facilities in the country, a status built on the work of Marnett, Liebler, and Caprioli.
“This is not easy to find — three top scientists — all in one university,” Wang said.
The university is also well-equipped for proteomics work. According to Marnett and Liebler, the university’s Mass Spectrometry Research Center has 36 mass spectrometers, mostly from Thermo, Liebler said, of which about 30 are used for proteomics research to some degree, including 10 that are dedicated solely for proteomics.
All the instruments are equipped with a liquid chromatographer, and the center is equipped with a robotic 2D-gel system and robots for automated sample preparation.
“We have just about everything, except we have not chosen to pursue array technology in the context of proteomics,” Liebler said, explaining that he and his colleagues are not yet convinced the technology can yield meaningful results.

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