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Richard Caprioli, Ph.D., co-director of the Vanderbilt team, directs the Mass Spectrometry Research Center and has helped pioneer the technology used to identify and analyze protein biomarkers in tissue samples.
Gordon B. Mills, M.D., Ph.D., director of the Robert J. Kleberg, Jr. and Helen C. Kleberg Center for Molecular Markers at the University of Texas M. D. Anderson Cancer Center, is collaborating with the Vanderbilt researchers.
“A lot of the differences between proteins in disease states and normal health are not differences in the amounts of the proteins themselves, but in the modified forms of proteins that are present,” explains Liebler. Abnormal genes, for example, may encode abnormal proteins, which in turn, trigger a cascade of events leading to cancer.
“Proteins are commonly dressed up in many different kinds of modifications that control their activity and function,” he says. “And so the problem is not so much in identifying the proteins but it’s frisking them, being able to detect differences in modified protein forms.”
Vanderbilt’s approach to frisking is called “shotgun proteomics,” in which proteins from a biological sample are cut into small pieces called peptides, analyzed using mass spectrometry techniques, and then put back together.
“Everybody has their own way of doing shotgun analysis,” says Liebler, adding that his team’s goal is to standardize the technology.
The standardization effort mirrors approaches being developed for early detection of colorectal cancer in the Jim Ayers Institute for Precancer Detection and Diagnosis. Liebler also directs this institute, part of the Vanderbilt-Ingram Cancer Center.
Other Vanderbilt researchers have found proteomic “signatures” that potentially may improve the early diagnosis and treatment of lung cancer, and they are scanning protein profiles found in the blood of African-American and Caucasian women for clues to why African-Americans die more frequently from breast cancer.
Proteomics “is an incredibly promising field,” said Barker, “but until we get some standardization here, it’s just not going to move forward.
“If we can move this field forward, we believe we can actually diagnose cancer very early,” she added. “If we diagnose it very early, we can start to really reduce the burden of this disease and ultimately, potentially, make it history.”
To learn more about Vanderbilt’s proteomics program, go to: www.mc.vanderbilt.edu/msrc.
For more on the federal initiative, visit http://proteomics.cancer.gov.