Spotlight on Nancy Colburn, Ph.D.

Spotlight Archive

By Maritta Perry Grau

You may have noticed a tall, slender redhead with an athletic build, easy smile, and a light step around campus: Dr. Nancy Colburn, Chief of the Laboratory of Cancer Prevention (LCP), part of the Center for Cancer Research (CCR), NCI-Frederick.

Talk with Dr. Colburn a few minutes, and you'll also realize here is an accomplished woman with varied interests, whether it's researching molecular targets for cancer prevention, running up a steep mountain trail for exercise, or trekking to a remote location for vacation.

These diverse interests are only a few facets of the whole woman. One facet is the focused cancer researcher. According to the LCP Web site, LCP investigators study "the molecular basis of cellular processes that, when perturbed, can lead to cancer induction and progression... Discovery and characterization of molecular targets for cancer prevention and intervention [are] common areas of interest among the seven principal investigators in LCP," each of whom—including Dr. Colburn—heads a lab section.

 To validate known molecular targets or discover new ones, Dr. Colburn and her colleagues use mice genetically engineered for resistance to carcinogenesis, subsequently testing the functional significance of the targets in mouse and human cell line transformation and invasion assays.

Discovery and Validation of New Molecular Targets

As part of the facet of the focused researcher, Dr. Colburn supervises the LCP's Gene Regulation Section. There, she and her colleagues investigate the molecular biology of multistage carcinogenesis in order to "understand gene regulation events that occur during rate-limiting phases of carcinogenesis and to target these events for prevention. Two categories of genes are being examined: 1) those controlled by transcription factors AP-1 or NFkB; and 2) those that are differentially expressed during neoplastic progression," the LCP Web site states.

She considers her greatest accomplishment the discovery and validation of two new molecular targets for cancer prevention: The transcription factor AP-1 and the translation factor inhibitor Pdcd4. In a series of groundbreaking articles (Cmarik et al., PNAS 1999; Jansen et al., Cancer Res 2005; Schmid et al., Cancer Res in press 2008) Dr. Colburn demonstrated that Pdcd4 functions as a tumor suppressor in mice and that its loss is prognostic for poor survival of colon cancer patients (Mudduluri et al., Cancer 2007).  Its molecular mechanism of tumor suppression was identified (Yang et al., Mol Cell Biol 2003, 2004; LaRonde-LeBlanc et al., Mol Cell Biol 2007), as was the process by which this tumor suppressor is inactivated during carcinogenesis (Dorello et al., Science 2006; Schmid et al., Cancer Res 2008). Thus, stabilizing Pdcd4 or using it as a gene therapy reagent (already efficacious in mice) could prove valuable as a strategy for cancer prevention or intervention.

 New Translational Initiatives

Dr. Colburn's laboratory also pursues major new translational initiatives. For example, LCP is engaged in collaborative parallel studies using nutritional or drug interventions to prevent colon carcinogenesis in both mice and humans. "These studies allow us to ascertain the molecular targets that are important to the efficacy of the intervention. They also allow us to identify predictive biomarkers that tell us whether the intervention will be successful in preventing cancer long before the cancer develops, and in individualizing the intervention to likely responders," she explained.

 Music and Sports Relieve Stress

Another facet of Dr. Colburn's persona is her interest in myriad avocations. To relieve stress and to relax, Dr. Colburn and her husband enjoy music, sports, traveling to exotic places, and of course, visiting with their daughters and their families (where they also ski).

 "Music, both piano in chamber music ensembles and singing in choirs, has been an avocation for decades, and we enjoy attending concerts and plays wherever we are. Since the 1970s, I have been doing three-mile road runs every other day. Since 1990, I've been doing trail running in the mountains, about two hours on the Catoctin Trail or the Appalachian Trail, perhaps twice a month. Of course, I enjoy skiing in Colorado where I also get to see my daughters and their families. Sea kayaking and traveling with my husband round out the list," she said of her special, nonscientific interests.

Dr. Colburn's favorite vacations have been to exotic places. Last summer, she and her husband explored Polynesian culture in Samoa. They've also visited Chile, where they came close to Antarctica. Both Antarctica and New Zealand are high on her "bucket list."

"New Zealand would be interesting for its Polynesian culture and for trekking. My husband and I have enjoyed Polynesian culture - art, music, dancing, and food - in Hawaii, on Easter Island (Rapa Nui, the home of rapamycin) and in Samoa," she said. Rapamycin, by the way, is a strong immunosuppressant drug given to prevent the body from rejecting an organ or bone marrow transplant and may be useful to treat cancer, due to its antiproliferative properties.

On one trip to Chile, she found herself skiing at Portillo in August, at the same time as the U.S. and Austrian ski teams, who were there to practice for the 2002 Olympics.

Another time, she and her husband were part of a small group with a Chilean guide, hiking and climbing in the Torres del Paine National Park, in Patagonia, southern Chile. According to the Web site http://www.gochile.cl/html/Paine/TorresDelPaine.asp, the park is considered "one of the most beautiful, unspoiled and remote places of the planet" with mountains that are described as sheer granite towers. The park is not for the faint-hearted; hiking is rugged and it can be cold and windy. Although highs may reach 75° F, the average summer temperature is a little over 52° F, and can drop as low as 33° F.

 Dr. Colburn noted, "We climbed up to the famous Torres and saw them against a beautiful blue sky. The Torres del Paine National Park is close to but north of Antarctica." So she came close to her dream of visiting Antarctica.

 In 1978 UNESCO declared the Torres del Paine National Park a "Biosphere Reserve," which the Web site Wikipedia defines as "an international conservation designation given by UNESCO under its Program on Man and the Biosphere." So far, 529 biosphere reserves have been established in 105 countries to show how humans can live in harmony with nature; each reserve comprises "combinations of terrestrial, coastal, or marine ecosystems."

 Lifelong Interest in Science

Another scientific facet is the woman with a lifelong attraction to science. Dr. Colburn can hardly remember a time when she wasn't interested in science. An undergraduate chemistry major, she went on to a Ph.D. at the McArdle Laboratory for Cancer Research, University of Wisconsin. The 1960s "was a great time to be doing molecular biology and molecular carcinogenesis research," she observed.  "Among my teachers were Nobel Laureate Howard Temin, and the originator of 5-Fluorouracil, Charlie Heidelberger."

 Armed with her Ph.D. and experience at the universities of Delaware and Michigan, she joined the NCI-Bethesda Laboratory of Experimental Pathology in 1976, becoming Chief of the Cell Biology Section, Laboratory of Viral Carcinogenesis, in 1979; and came to NCI-Frederick in 1980 with the Laboratory of Viral Carcinogenesis. In 1996 she became Chief of the Gene Regulation Section, Laboratory of Biochemical Physiology; and in 2003 she was appointed Chief of LCP.

 Professional Achievements

A fourth facet is the born organizer. Dr. Colburn has organized several major international symposia, including those for Keystone, the Federation for American Societies for Experimental Biology, and the American Cancer Society (ACS). She has also served on NIH RO-1 and PO-1 study sections and 40 NIH or ACS site visit teams, chairing many of them. She has served on numerous journal editorial boards; been an invited speaker at many conferences and universities; served on scientific advisory boards at several cancer centers and medical schools; served on the Board of Directors of the American Association for Cancer Research; and has served as president of Women in Cancer Research. In addition, she has chaired the CCR's Cancer Prevention Faculty and the NCI-Frederick Distinguished Scientist Speaker Series. She is also a member of the CCR's Promotion Review Panel and multiple search committees.

 Dr. Colburn has garnered several awards, including Distinguished Professorships at the University of Texas—Galveston, the University of Nebraska Medical School, Yonsei University Medical School, and the University of Texas—MD Anderson Cancer Center; an NIH Merit Award 2002; and an NCI Outstanding Mentor Award 2002.

 Building Collaborations

Finally, there's the facet of working well with others. The future of research looks bright for Dr. Colburn, LCP, and their collaborators.

 "We hope to continue to build productive partnerships between the LCP and others in the CCR, with other NCI divisions, including the Division of Cancer Prevention and the Developmental Therapeutics Program, the NCI/NIH Imaging initiatives, and others. With these interdisciplinary efforts, we can demonstrate some unique possibilities that might be extended to the extramural community," Dr. Colburn concluded.

Maritta Perry Grau, Editor
Scientific Publications, Graphics & Media
SAIC-Frederick, Inc.
National Cancer Institute at Frederick

Photography Department
Scientific Publications, Graphics & Media
SAIC-Frederick, Inc.
National Cancer Institute at Frederick

Jillian DeShazer
Web Graphics and Development
Computer & Statistical Services
Data Management Services, Inc.
National Cancer Institute at Frederick