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Pitt couple wins top prize for cancer research

Tuesday, June 10, 2003

By Byron Spice, Post-Gazette Science Editor

A decade ago, Yuan Chang and Patrick S. Moore had a plan to find the infectious agent they thought was causing a common type of cancer in people with AIDS. What they didn't have was money.

Patrick S. Moore and Yuan Chang in their lab at the Hillman Cancer Center in Shadyside. (Martha Rial, Post-Gazette)

But by scraping together some money and working long hours -- "We more or less had to do this on the side," Moore recalled -- the husband-wife team of M.D.'s was able to identify the virus that causes Kaposi's sarcoma. It made their scientific reputations, opened doors to money for further research and now has won them one of the world's most prestigious awards for cancer research.

Chang and Moore will receive the $250,000 Charles S. Mott Prize in an awards ceremony tomorrow that caps the General Motors Cancer Research Foundation's annual scientific conference in Washington, D.C. The GM foundation awards the prize each year for outstanding contributions related to the cause or prevention of cancer.

The two researchers, co-directors of the Molecular Virology Program at the University of Pittsburgh Cancer Institute, learned of their selection in a phone call April 4.

"It was out of the blue," Chang said yesterday as she and Moore prepared to leave for Washington.

"This award is one of the top annual awards in cancer research internationally as well as one of the most prestigious prizes ever awarded to a University of Pittsburgh faculty member," Dr. Arthur Levine, senior vice chancellor for the health sciences, said in a statement released yesterday. Nine previous winners, he noted, have gone on to win Nobel prizes.

Moore, professor of molecular genetics and biochemistry, and Chang, professor of pathology, joined the Pitt cancer institute last summer, moving from Columbia University, where they discovered the cancer-causing virus, known as Kaposi's sarcoma-associated herpesvirus, or KSHV.

When they began their groundbreaking work in 1992, Chang and Moore were married, but had never done a joint research project together. At the time, Chang was a researcher at Columbia and Moore was New York City's deputy commissioner for health.

As the AIDS epidemic had progressed, evidence had accumulated that Kaposi's sarcoma was caused by an infectious agent, Chang noted. A rare cancer that typically affects the skin but also can strike internal organs, Kaposi's sarcoma was 200,000 times more likely to occur in AIDS patients and, among those patients, gay men had a 20-fold higher risk.

"It really looked like there was a subepidemic in the AIDS epidemic," said Chang, noting that it appeared to be caused by something that was sexually transmissible.

She and Moore weren't sure exactly what they were looking for, but were convinced they knew how to find it.

They settled on a nifty technique involving molecular biology -- comparing the DNA extracted from a Kaposi's lesion to the DNA extracted from healthy tissue removed from elsewhere on the same patient. By eliminating all of the DNA that was common to both the tumor and the healthy tissue, they reasoned, they would be left with DNA unique to the tumor and with an important clue about the cause of the cancer.

"You can't really get funding for something this speculative," Moore said. But by working together on a shoestring, they were able to isolate a bit of DNA. It turned out to be a herpesvirus, which would later be dubbed KSHV. Further research showed the same virus also is linked to other disorders, including a cancer called B cell lymphoma.

"Few scientists can lay claim to have truly found the cause of a cancer," said Dr. Ronald Herberman, director of the cancer institute.

More recent work with the virus has focused on how it interacts with the body's disease-fighting immune system. In work published last fall, they showed that in its attempts to evade the immune system, the virus disables the machinery in cells that normally suppresses tumor growth, thus causing the cell to turn malignant.

They are continuing to analyze this phenomenon, which might eventually lead to new cancer treatments. They also plan to continue looking for infectious agents that cause cancer, though that work remains on hold until they can get a containment lab up and running at the Hillman Cancer Center. The containment facility, which would prevent infectious agents from escaping the lab, should be ready and certified by late summer, Moore said.

Moore and Chang, both graduates of the University of Utah School of Medicine, never planned to work together, but the scientific partnership that developed at Columbia has proven fruitful.

"The nice thing about working with each other," Moore said, "is we're able to continue our work at home."

"And," Chang quickly added, "it's one of the bad things about working together. It would be nice to get away from it at times."

"We're always talking about science," Moore said, describing their working relationship as "pretty novel." Some of their most productive discussions, both agreed, occur while in their car.

"It gets too crazy in the lab," Chang explained.

Byron Spice can be reached at bspice@post-gazette.com or 412-263-1578.

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