For a physician who originally gave little thought to performing research, Shelly Lu has proven to be remarkably good at it.

Good enough that Lu, professor of medicine, division of gastrointestinal and liver diseases at the Keck School of Medicine of USC, recently received – for her work related to colon cancer – a new $1.99 million National Institutes of Health R01 grant. She also successfully renewed another $2 million NIH RO1 grant at the same time.

Moreover, in a discipline where holding even one prized RO1 grant is considered laudable, and holding two remarkable, Lu now serves as principal investigator on a total of five such grants, totaling $9.2 million. She has received 16 years of uninterrupted NIH funding totaling $17.7 million.

Edward Crandall, chair of the Department of Medicine, called Lu’s work impressive in both its scope and importance.

“In this time of such intense competition for NIH funding support, Dr. Lu’s remarkable achievements, which reflect on the outstanding quality of her research program, are especially noteworthy,” he said.

For Lu, a devotion to research developed over time and in large part because of the influence of her longtime mentor Neil Kaplowitz, director of the USC Center for Liver Diseases, chief of the division of gastrointestinal and liver diseases and the USC Associates/Thomas H. Brem Chair of Medicine at the Keck School.

Lu said that as a second-year resident, she received from Kaplowitz an invitation to work in his lab on antioxidant transport research. Later, with his encouragement, Lu chose to apply for a gastrointestinal fellowship and continue on his research team.

“A lot of things in life you don’t plan,” Lu said. “Originally, I was just going to be a doctor – and not even necessarily a gastroenterologist. But having met him at that time was very fortuitous: That’s how I got into basic research.”

Lu, who later worked at Cedars-Sinai before joining USC in 1990, is now associate director of the NIH-funded USC Research Center for Liver Diseases and associate editor of the journal Hepatology.

While at USC, her research has focused on methylation in liver disease and the role of the enzyme methionine adenosyltransferase (MAT), and its different forms, in healthy liver function and disease.

MAT sets in motion the synthesis of S-adenosylmethionine, a substance commonly known as SAMe (pronounced “sam-ME”). The compound is manufactured in all human cells and regulates critical cellular processes such as gene expression, cell growth and death.

Lu’s newest RO1 grant focuses on how SAMe controls these critical cellular processes, specifically in colon cancer cells.

SAMe is also crucial to the liver’s function – if too much or too little is present, liver injury and cancer can result. Also of particular interest, Lu said, is that SAMe – a widely available nutritional supplement in the United States – is well tolerated by the body at high doses and also selectively kills colon cancer cells but not normal colon epithelial cells.

As a result, it could be useful in the prevention and treatment of colon cancer.

“This is exciting as there is currently no chemopreventive agent that is free of side effects,” she said.

Additionally, SAMe may prove effective as an adjunct to colon cancer treatments, making chemotherapeutic agents more effective at lower doses – another key focus of Lu’s current research.

In recognition of her research success, Lu was inducted into the American Society for Clinical Investigation in 2002 and the American Association of Physicians in 2006.

The society recognizes physician-scientists with outstanding achievements in biomedical research. The association honors members for their advancement of scientific and practical medicine. Inductees have included Nobel laureates and members of the National Academy of Sciences and the Institute of Medicine.

In May, the American Gastroenterological Association named Lu one of its Outstanding Women in Science honorees for 2008.

Lu said that although she may not have intended to enter a career in research in the beginning, she has no regrets at having done so – because it has provided a continuing opportunity to translate advances in the lab into better care for patients with liver diseases and to help prevent and treat colon cancer.

“I have had a most challenging and rewarding career as a physician-scientist, and I am immensely grateful for it,” Lu said. “There is never a boring moment.”