By Ashley DeVine, Staff Writer
Although Nancy Colburn, Ph.D., retired in January after 36 years at NCI, she won’t be disappearing from the NCI campus at Frederick anytime soon; she’s been appointed scientist emeritus in the Laboratory of Cancer Prevention (LCP), Center for Cancer Research (CCR).
Beginning of a Career in Molecular Biology
Colburn received her Ph.D. in biochemistry from the McArdle Laboratory for Cancer Research, University of Wisconsin, in 1967. “It was really exciting in the mid-60s to be studying molecular biology. Everything was so new. Who could imagine such exciting discoveries about how genetic information got communicated and transmitted?” she said.
Colburn’s career began in academia. She taught for four years at the University of Delaware and three years at the University of Michigan. “I feel it’s really valuable to have experience in the academic world when you’re going to be a principal investigator (PI) in the intramural program,” she said. “Every time I wrote a grant—at Delaware, at Michigan, and here—I got high scores and was funded. You have to have that kind of credential in order to be appointed to a grant study section.”
From Teacher to Researcher
Colburn came to work at NIH in 1976. She intended to stay for a few years before going back to teaching. “I got a job offer to go to Purdue, and I was all set to go in 1979,” she said. Then George Todaro offered her a principal investigator position in the Laboratory of Viral Carcinogenesis, in Bethesda. “My lab got started for the first year in Building 37, and then we were told we were going to move to Frederick,” she said.
In 1996, Colburn decided to leave the Laboratory of Viral Carcinogenesis, and she was able to take her resources with her. She became chief of the Gene Regulation Section, Laboratory of Biochemical Physiology. In 1998, Colburn moved to the Basic Research Laboratory, where she stayed until she was appointed chief of LCP in 2003.
Discovering New Molecular Targets for Cancer Prevention
Much of Colburn’s career as a researcher has been spent conducting gene regulation studies, she said. She considers her greatest accomplishments to be the discovery and validation of two new molecular targets for cancer prevention: tumor-suppressing translation inhibitor Pdcd4 and oncogenic transcription factor AP-1.
“We discovered Pdcd4 using a cell culture model that I had generated, which was one-of-a-kind—it’s the only one in the world that’s ever existed—that allows you to study tumor promoter–induced transformation,” Colburn said.
She explained that in a cell culture model, one cell line is genetically sensitive and the other is genetically resistant. “If you find out what’s happening in the sensitive line that’s not happening in the resistant line, it’s likely to be an oncogene. If you find out what’s happening in the resistant line that’s not happening in the sensitive line, it’s likely to be a tumor suppressor,” she said.
Colburn’s lab also showed that Pdcd4 was a tumor suppressor in genetically engineered mice, and this discovery was translated to human cancers. “In just about every kind of cancer known to man, what happens is that the Pdcd4 goes away during carcinogenesis,” she said. “Two different mechanisms cause it to disappear—that gives you a therapeutic possibility because what you’d like to do is target those mechanisms to keep Pdcd4 from disappearing.”
In studying the role of transcription factor AP-1 in carcinogenesis and cancer prevention, Colburn’s lab discovered that AP-1 activation is required to promote tumor cells in a cell culture model and to promote skin tumors in vivo. Targeting AP-1 for tumor prevention was then extended to mouse and human models and human-relevant exposures, such as human papilloma virus and UVB.
Colburn’s lab also conducts dietary intervention studies to discover biomarkers of colon cancer in mice and humans. The results of one study of obese and non-obese mice fed a diet enriched with beans showed that colon carcinogenesis was decreased in the obese mice. The results also revealed potential serum biomarkers of efficacy, Colburn said. Efficacy, or response, indicators are important for targeting the intervention to those likely to benefit.
Achievements and Awards
In 2000/2001, Colburn approached the director of the intramural NCI with an idea to form a mouse models for cancer prevention faculty. At the time, the director wanted to form faculties of basic and clinical researchers to promote collaboration.
“The idea of it was that if you engineer the mice right, you can go through a whole lot of experiments to show that they model real human cancer and that they can therefore be used for asking questions about drugs, drug discovery, and drug development,” she said.
Colburn earned an Animal Models for Cancer Prevention Working Group Merit Award in 2002 for developing this faculty.
The mouse models for cancer prevention faculty became the Cancer Prevention Faculty (to include a human translational focus) and held retreats in 2001, 2003, and 2005. “We would get three or four people to speak at a session, typically a basic scientist, a translational scientist, and a clinical scientist,” Colburn said. “This stimulated people to start up collaborations you never would have imagined.”
Another memorable NIH conference for Colburn was the Molecular Targets for Cancer Prevention event at Natcher Auditorium in 2009. “We had some outstanding speakers from all over the country, as well as internal speakers,” she said. “The big thing about cancer prevention is that it’s more successful than cancer treatment. Cancer treatment once the cancer is already somewhat advanced is very difficult; you have to try to turn back so many things that have gone wrong.”