Profile: Raymond DuBois, M.D., Ph.D.
Conquest - Summer 2007
By Mary Jane Schier
Discovering a textbook on the molecular basis for medicine in the Texas A&M University library was a defining moment for young Ray DuBois in 1975.
“I had no experience in medicine or science,” DuBois remembers, “and it intrigued me to read that certain biomolecules were known to exist and could play a role in disease.”
Raymond N. DuBois, M.D., Ph.D., is collaborating with Wei Zhang, Ph.D. (left) whose team is using sophisticated microarray technology to scan genes for abnormalities.
Today, Raymond N. DuBois, M.D., Ph.D., is an internationally respected physician-scientist whose translational research has advanced understanding of the molecular and genetic aspects of colon cancer. His research during the 1990s demonstrated how the prostaglandin biosynthetic pathway produces inflammatory mediators that promote colorectal cancer and led to an important clinical trial showing the drug Celebrex® can reduce pre-cancerous colon polyps. Findings from his laboratory are helping other investigators develop promising cancer prevention and treatment strategies.
DuBois’ latest milestone occurred in June when he came to M. D. Anderson as the new provost and executive vice president for academic affairs. His responsibilities include directing the institution’s extensive research and educational programs along with managing all faculty recruitment, resourcing and mentoring activities.
“M. D. Anderson is a phenomenal cancer center with a global operation and an unparalleled record of translational research. We’re in an exciting new age of cancer research, and I’m honored to be joining this fantastic faculty and staff who are totally dedicated to changing the face of cancer,” DuBois says.
Before moving to M. D. Anderson, DuBois directed the Vanderbilt-Ingram Cancer Center in Nashville. He also was the B.F. Byrd Jr. Professor of Medical Oncology and a professor of medicine, cell developmental biology and cancer biology at Vanderbilt University Medical Center.
DuBois began his academic research career in 1991 as an assistant professor at Vanderbilt and was promoted to full professor in six years. During that time, his laboratory identified and characterized the cyclooxygenase-2 (COX-2) gene as important in intestinal epithelial cell growth and transformation. His team was the first to define a series of critical molecular steps involved in COX-2 expression. They later discovered the interaction between the prostaglandin and epidermal growth factor receptor signaling pathways, thereby providing a rationale for combining a variety of different inhibitors that may prevent and/or treat colorectal and other cancers.
DuBois is an internationally respected physician-scientist whose translational research has advanced understanding of the molecular and genetic aspects of colon cancer.
In 1997, the DuBois team found COX-2 selective inhibitors blocked human colon cancer cells from growing in the laboratory. That finding facilitated the notable clinical trial – conducted at M. D. Anderson and St. Mark’s Hospital in London – which showed the COX-2 inhibitor Celebrex could reduce polyp burden in familial adenomatous polyposis (FAP) patients. FAP is a genetic disorder that leads to numerous pre-cancerous polyps in the colon. Based on that study, the drug was approved by the U.S. Food and Drug Administration for treating patients with FAP.
“I’ve enjoyed working with many investigators at M. D. Anderson over the years,” says DuBois, one of 17 authors who reported findings from the historic clinical trial published in the June 2000 issue of the New England Journal of Medicine.
From 1998 to 2004, DuBois directed the Division of Gastroenterology, Hepatology and Nutrition at Vanderbilt. While broadening his own research, he earned a reputation for leadership marked by substantial growth in faculty, with more than a doubling of the division’s research funding and clinical revenue during his tenure. Major grants included a National Cancer Institute Program Project award for the discovery of novel cancer prevention targets and a National Institutes of Health Digestive Disease Research Center grant, one of only 16 in the country. In early 2005, he was selected to serve as the second director of the Vanderbilt – Ingram Cancer Center, which was established in 1993.
Leaving Vanderbilt was not an easy decision.
“We were in a period of substantial growth, had great faculty conducting outstanding research, and I had many plans. But in the final analysis, I felt that joining M. D. Anderson would allow me to have a bigger impact on the worldwide problem of cancer,” DuBois explains.
In addition, he confides, “a part of my heart had never left Texas.”
DuBois was raised in Runge, Texas, a small farming and ranching community about 75 miles southeast of San Antonio. The third of six children, he was named for his father, who worked in the South Texas oil fields while his mother operated a roadside icehouse. His first two jobs were selling watermelons and chopping cotton.
During high school, he raised steers for a Future Farmers of America project. One steer was chosen grand champion at the Runge Livestock Show, and others did so well at the Houston Livestock Show and Rodeo that DuBois received a four-year scholarship to the Texas college of his choice.
As a young boy, DuBois (right) raised prize-winning steers. His success earned him a four-year scholarship to the Texas college of his choice.
“Winning that scholarship was the most momentous event in my life because there was no way my parents could afford to pay for college,” says DuBois, whose original major at Texas A&M was agriculture education. He also was supported by a National Honor Society scholarship.
After switching to biochemistry and reading about the molecular basis for medicine, DuBois worked in the laboratory of Edward D. Harris, Ph.D., a professor of biochemistry and biophysics known for his research on the molecular action of copper. It was an unforgettable period for both the Aggie student and his professor.
“It didn’t take me long to get hooked on doing the lab projects,” DuBois reminisces. “For Dr. Harris, I investigated the role of copper in the development of chick blood vessels.”
More than three decades later, Harris reflects, “Many students taking the introductory course to research don’t like the nitty-gritty of the lab, but Raymond was the exception. Right away, I could see he had a strong aptitude and keen interest in everything. He was so excited that we could actually control and regulate cell growth, and he helped me determine that a lack of copper in the chicks’ diet caused their blood vessels to rupture.”
After getting his bachelor’s degree in biochemistry in 1977, DuBois went to The University of Texas Southwestern Medical Center at Dallas for his Ph.D. in biochemistry, which he received in 1981. He earned his medical degree in 1985 from the UT Health Science Center at San Antonio. Between 1985 and 1991, he completed a residency in internal medicine and fellowship in gastroenterology at The Johns Hopkins Hospital and was a Howard Hughes research associate at Johns Hopkins Medical School.
“A really significant moment for me was the chance to work in the lab of Nobel Laureate Daniel Nathans at Johns Hopkins,” DuBois says.
Known as one of the fathers of molecular biology, Nathans was a demanding mentor who expected trainees to work long hours on difficult gene-cloning projects. DuBois thrived in that environment because “I finally could put all my training together and see how basic science can apply to clinical disease.”
Within a few years of going to Vanderbilt, DuBois discovered the link between COX-2 and cancer progression. Having lost his father to lung cancer added a personal incentive to understand the differences in genes that regulate normal and abnormal cells. It turns out that COX-2 inhibitors may have a role in lung cancer treatment as well as colorectal cancer prevention.
Among his numerous honors was induction into the Royal College of Physicians of the United Kingdom in 2000. In May 2007, he was inducted into the Johns Hopkins Society of Scholars. He is president-elect of both the American Association for Cancer Research and the International Society for Gastrointestinal Cancer.
Currently, DuBois is principal investigator on three NIH grants, including a 10-year renewable MERIT (Method to Extend Research in Time) Award from the National Institute of Diabetes and Digestive and Kidney Diseases. He has transferred these and other projects to his new laboratory in M. D. Anderson’s Smith Research Building, where several junior faculty and postdoctoral fellows have joined him.
“Keeping my laboratory functioning at a very high level is important and will allow me to stay attuned to the issues facing all investigators at M. D. Anderson,” DuBois says. In addition to his executive roles, he is a professor in the Department of Gastrointestinal Medical Oncology.
DuBois cites marrying Lisa Abrams in 1980 and having two children as “the best of all my milestones.” His wife has been a freelance writer for many years, and her first book tracing the founding of Vanderbilt Children’s Hospital will be published soon. Their daughter Shelley recently received a degree in bioanthropology from the University of California, San Diego, and son Ethan is a high school senior.
DuBois says his wife, Lisa, and their two children, Shelley and Ethan, are the “best of all my milestones.”
At M. D. Anderson, DuBois succeeds Margaret L. Kripke, Ph.D., former executive vice president and chief academic officer. She remains on the faculty in a part-time capacity and continues her national leadership on the three-member President’s Cancer Panel.
DuBois is the first executive to have the title of provost.
“We’ve chosen this title to reflect the importance of our expanding research endeavors, our degree-granting status, and the climate of scholarship and discovery that we strive to achieve in all mission areas,” explains John Mendelsohn, M.D., president of M. D. Anderson.
DuBois believes he’s joined M. D. Anderson “in an exhilarating period when progress is being made faster through translational research and the face of cancer is changing. I expect survival rates for cancer to keep improving and for many cancers to be detected earlier while most treatments will get much better. And I am particularly optimistic about the increasing number of targeted therapies emerging from our laboratories that must be brought forward for clinical testing.”
At the same time, DuBois worries about decreasing federal support for research and its impact on recruiting young people into cancer-related fields.
“It’s crucial to intensify our efforts to expand funding for cancer research so we don’t lose any of our momentum,” he stresses. “Nothing would be more tragic in our battle to treat and cure cancer than to lose a generation of brilliant young scientists because they couldn’t get funding for their valuable and worthy projects.”
Conquest - Summer 2007