High-tech surveillance

The power of proteomics

Bill Snyder
Published: February, 2007

A montage of molecular images glows with a spectrum of peptides and proteins, their colors assigned to different molecular weights, in sections of a rat brain.  Images like these, which were produced by MALDI imaging mass spectrometry, can reveal the distribution of individual proteins in cells and tissues.
Image courtesy of Malin Andersson, Ph.D., research fellow in the Vanderbilt Mass Spectrometry Research Center
Will fingerprinting cancer lead to its arrest?

That’s the hope of proteomics, the science of proteins.

Researchers are trying to identify patterns of proteins in blood and tissue samples that reflect the presence of diseases like cancer in the body. These patterns, often called “molecular fingerprints,” could serve as biomarkers for early detection.

“We believe that the future of medicine is actually going to depend very heavily on the ability to discover and validate biomarkers in proteomics,” Anna D. Barker, Ph.D., deputy director of the National Cancer Institute (NCI), said during a news conference in 2006.

By improving early detection, biomarkers could increase the chances for successful treatment and survival, noted Nobel laureate Leland Hartwell, Ph.D., president and director of the Fred Hutchinson Cancer Research Center in Seattle.

In addition, “they will be useful for managing the cancer process at all stages, from risk assessment to early detection to prognosis to therapeutic response and disease recurrence,” he said.

Currently, however, there is a lack of standardization of techniques used to analyze proteins. As a result, “the overall reliability of the approach is not currently sufficient to apply it directly to clinical research,” says Daniel C. Liebler, Ph.D., director of the Proteomics Laboratory in the Vanderbilt Mass Spectrometry Research Center.

Liebler is heading up one of five teams across the country to standardize proteomic technologies and move them forward. The project, part of the NCI’s Clinical Proteomics Technologies Initiative, was announced during last fall’s news conference.

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.

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