Protein power -MUSC pushes ahead in emerging science of proteomics

Dr. Dan Knapp isn't about to remove the door to his office at MUSC, but the stream of researchers flooding in from just about every corner of the campus nowadays is getting heavy.

Knapp is at the epicenter of studies at MUSC into a new realm in biotechnology: proteomics.

Two years ago, there were zero proteomics studies on campus. Now there are as many as 30, though Knapp is reluctant to provide an exact number on how many there are. "I could give you a number," the head of the university's Proteomics Center said, "but it would change tomorrow."

Proteomics is a hot topic among medical researchers not just at MUSC, but all over the country. Involving the large-scale study of the proteins that are made by genes, proteomics has exploded in the last couple of years, thanks in part to the completion of the Human Genome Project, which provided scientists with an important database of human genes.

The potential behind proteomics is huge. Imagine, for instance, detecting breast cancer with a simple blood test. Efforts to create tests using proteomics have already yielded a new way of detecting bladder cancer and could also lead to screenings for ovarian, lung and prostate cancers.

Down the road, proteomics could even allow physicians to tailor treatments to individual patients, so that those treatments are more effective and create fewer harsh side effects. The impact, experts believe, will be felt in all areas of medicine and could lead to lower health care costs and a healthier population.

The federal government is so excited about proteomics that it has pumped hundreds of millions of dollars into its study. Private-sector interests, particularly the pharmaceutical industry, are also getting on board.

Proteomics has even attracted the attention of Jerry Zucker, head of North Charleston's Intertech Group, a conglomerate with worldwide interests. "It's the big buzzword right now," Knapp said.

MUSC has spent the last few years establishing a foothold in the field. Two years ago, it received a 7-year, $15.2 million grant from the National Heart Lung and Blood Institute to develop a Cardiovascular Proteomics Center, one of 10 such grants the institute awarded around the country as part of a $157 million effort. MUSC then received another $3 million to help coordinate these centers. More recently, it received $4 million in state lottery funds to develop its Proteomics Center.

"I think it's one of the areas where we can be a true national leader," said Dr. John Raymond, MUSC's provost. "We have the equipment, we have the funding and we have the people who've had a long-standing and visible presence in the field."

Discovered in 1838 by Swedish chemist Jons Jacob Berzelius, proteins are complex organic compounds that are made up of amino acids and are the primary component of any living cell. Genes carry the code that make us who we are. Proteins carry out the instructions embedded in our genes. Scientists have studied the role of proteins for decades, but for the most part could study only a single protein at a time. Doing so often took many years.

That changed in the late 1980s when two scientists, American John Fenn and Japan's Koichi Tanaka, separately developed methods that allowed scientists to analyze large groups of proteins using a device called a mass spectrometer. The two shared the 2002 Nobel Prize in chemistry for their work. A mass spectrometer measures the mass of molecules very accurately.

"We call it a very expensive, very accurate bathroom scale," said Dr. Timothy Veenstra, director of the National Cancer Institute's Biomedical Proteomics Program. By calculating the weight, the equipment allows scientists to determine the identity of a protein.

But scientists can't understand fully the role of a protein without knowing the gene from which it came. That information has been provided by the Human Genome Project, the $3 billion, 15-year effort to map the 20,000 to 25,000 genes in the human body by the U.S. Department of Energy and the National Institutes of Health.

With the project practically complete in 2003, the two agencies announced they had sewed up the last of their work on the sequence last week. "Before, it would take you 10 years to identify 1,000 proteins," Veenstra said. And now, "Two days. Maybe a day."

Much of the early work in proteomics is focused on new diagnostic tests. Scientists do this by looking for "biomarkers," a biological indication of whether someone has a particular malady. There are a good number of such projects under way today at MUSC. One study is looking for the biomarkers of esophageal cancer. Another is looking for the biomarkers of heart hypertrophic obstructive cardiomyopathy, the condition most often associated with young athletes collapsing and dying while playing sports.

Dr. John Arthur, who heads the proteomics lab at the university's nephrology department -- the university recruited him more than three years ago to do just that -- is involved in many of the studies. One of them is looking at kidney disease. The ultimate goal, Arthur said, is to develop an easy urine test using a dipstick that can determine whether a patient has kidney disease. Right now, that disease is confirmed through a biopsy, a procedure that is far more difficult and invasive.

By developing new and easier tests, doctors could find out much sooner whether someone has a problem. That's especially important with certain diseases, such as cancer, where early detection is key to survival. "Often, we don't find a lot of cancers until it's too late," Arthur said. "It's difficult to treat them. The treatment is more invasive. If we could identify diseases in a much earlier stage, we could start earlier, the treatment is less toxic, and the outcomes would be much better."

Along those lines, scientists hope to be able one day to use proteins to predict which treatments will be most effective in certain patients. "It could save the pharmaceutical industry," Arthur said, noting that new proteomic-based tests for effectiveness and side effects could reduce the time it takes to get a drug to market.

This potential has attracted the attention of business. Zucker, for one, has contributed $100,000 to the university's Proteomics Center, fulfilling MUSC's private match requirement to be eligible for state lottery funds.

"(Proteomics) has the potential to simplify diagnoses and reduce the cost of medical care," he said. Not, in other words, a bad way to make money.

UNDERSTANDING PROTEOMICS

Essentially, proteomics is a biotechnology that analyzes how proteins work in the body. Proteomics aims to recognize protein patterns, the equivalent of fingerprints in the blood or tissue. These patterns can reveal whether you have cancer or some other life-threatening disease or condition. For instance, early in the development of cancer, normal cellular processes go awry, causing an overproduction of proteins that promote tumor growth. Understanding this process could help researchers develop tactics for interrupting the process, stopping cancer in its tracks, or for diagnosing it in its earliest stages.