$4.8 million grant launches massive proteomics feasibility study

Paulovich’s goal of measuring all human proteins similar to Human Genome Project
Dr. Mandy Paulovich
“If successful, this study could help to stimulate a larger international endeavor that would be comparable to the Human Genome Project,” said Dr. Mandy Paulovich, an expert in cancer proteomics. Photo by Susie Fitzhugh

The Clinical Research Division’s Dr. Mandy Paulovich has received $4.8 million in federal stimulus funding from the National Cancer Institute to co-lead a pilot study to assess the feasibility and scalability of a project that aims to measure all of the proteins in the human body.

“If successful, this study could help to stimulate a larger international endeavor that would be comparable to the Human Genome Project,” said Paulovich, an expert in cancer proteomics. She is co-leading the effort with Dr. Steven Carr at the Broad Institute in Cambridge, Mass. A senior adviser on the project is Dr. N. Leigh Anderson, founder and chief executive officer of the Plasma Proteome Institute in Washington, D.C.

“We hope that the long-term output of this effort—the human Proteome Detection and Quantitation (hPDQ) project—will allow us to build a method to measure the products of those genes, which are the more than 100,000 proteins in the human body,” Paulovich said.

Understanding the body’s protein landscape is important because proteins are the workhorses of the cell that carry out genetic instructions. Changes in the structure or abundance of proteins are associated with genetic mutations that cause diseases such as cancer.

Currently there is no good way to simultaneously measure large numbers of human proteins, which presents a major obstacle to progress in both basic and translational research. Unlike gene signals, which can be amplified in the laboratory, protein volume cannot be dialed up. Because many proteins are present in very low quantities—like a needle in a haystack—they are below the limits of detection with current techniques.

This study is designed to change that. “This pilot has the potential of developing the first step toward making the entire human proteome clinically accessible,” said Dr. Henry Rodriguez, director of NCI’s Clinical Proteomic Technologies for Cancer program.

“If we can create ways to measure a large fraction of human proteins, particularly those in very low abundance, this will facilitate the development of new drugs and personalized medicine,” Paulovich said.

Highly sensitive and targeted analytical technology—multiple reaction monitoring mass spectrometry—will be used to develop 400 tests to measure the levels of 200 proteins found in breast-cancer cells. While the study’s purpose is to test the feasibility of applying this technology on a much broader scale, a side benefit may be to determine whether certain proteins are associated with specific subtypes of breast cancer.

To maximize productivity, Paulovich and colleagues will closely coordinate activities and share their results with Dr. Robert Moritz, director of proteomics at the Institute for Systems Biology, who recently received federal stimulus funding to lead a related human proteome project.

[Adapted from a Hutchinson Center news release]

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