Raymond N. DuBois, MD, PhD
Hortense B. Ingram Professor of Molecular Oncology
Director for Cancer Prevention, Control, and Population-Based Research
Vanderbilt-Ingram Cancer Center
Professor of Medicine
Professor of Cancer Biology
Vanderbilt University Medical Center
It’s hard to imagine a world-class scientist in cancer prevention having his roots in Runge, Texas, population 800. But that is where Ray DuBois, who is currently credited with some of the most groundbreaking achievements in the field, grew up. Runge is a remote, one traffic-light town on the Southern plains of the Lonestar State. Today, Ray is exploring far different fields than the ranchland where he worked throughout his youth. He holds the position of Deputy Director for Cancer Prevention at the Vanderbilt-Ingram Cancer Center.
Just this year, Ray was honored with the Dorothy P. Landon Award in Translational Research, the highest distinction bestowed by the American Association for Cancer Research (AACR), which recognizes his seminal contributions towards understanding the role of cyclooxygenase-2 (COX-2) in cancer and the potential for COX-2 inhibition in preventing and treating cancer. John Minna, MD, the chair of the selection committee noted, “Of all the outstanding applicants nominated for this award, Ray’s work stood out as the most significant in terms of its impact on patients as he successfully took a very basic finding all the way to the clinic.” The year 2004 also brought Ray another award, the American Gastroenterological Association’s 2004 Distinguished Achievement Award for his accomplishments in the field of digestive disease research.
Upon learning of his selection as the recipient of these honors, Ray said, “I couldn’t have been more surprised and humbled to learn that I’d been chosen to receive both of these awards in the same year. Both are a tremendous honor. Throughout my career I have had the great fortune to be associated with outstanding laboratory staff, students, postdocs, and collaborators. They have made this work possible and have kept the faith, even in the early days when many people considered the field of chemoprevention a scientific fantasy.”
The road from Runge to Vanderbilt and the road from basic research to clinical application have been marked by much achievement, and some twists and turns. Ray had his first taste of the possibilities presented by the larger world when he won a 1973 Texas Livestock Show and Rodeo Scholarship, which paid for a full four-year education at the in-state college of his choice. He chose Texas A & M. Initially, Ray planned to major in agricultural education. However, after taking an honors biochemistry course during his junior year, he changed his mind, which, in some respects, changed the course of biochemical research for decades to come. He switched majors and concentrated on deciphering which intracellular signaling pathways were activated in cells treated with epidermal growth factor (EGF). He later completed a PhD in biochemistry at the University of Texas Southwestern Medical Center in Dallas, where he focused on the molecular mechanisms responsible for the induction of cytochrome-P450 and P450-side-chain-cleavage enzyme in response to drug or hormone treatment. There, he met and married his wife, Lisa, who was a graduate student in biomedical communications.
His interest in the clinical impact of alterations in biochemical pathways on disease, particularly in the gastrointestinal (GI) tract, led Ray to pursue a medical degree at the University of Texas Health Science Center at San Antonio. He spent one summer during medical school working in the laboratory of Dr. Theresa Stadtman at the National Institutes of Health (NIH), an experience that increased his determination to pursue an academic research career.
Ray then traveled to Baltimore to Johns Hopkins Hospital for his internship and residency. Ironically, the first person he met at Johns Hopkins was Marschall Runge, a resident whose ancestors were responsible for settling Ray’s tiny Texas hometown. He considers his postdoctoral training at Johns Hopkins a defining moment in his biomedical career: “I had the early training, the PhD in biochemistry, and all the clinical training. During that postdoc period, I could put it all together and see how basic science can apply to real clinical disease.”
Upon completing his fellowship training, Ray accepted his first faculty position as an assistant professor at Vanderbilt University Medical Center in Nashville. Heading up his own laboratory, he soon began investigating the identification and characterization of the COX-2 gene and its role in intestinal epithelial biology. His laboratory was the first to demonstrate that upregulation of the COX-2 enzyme leads to inhibition of apoptosis, stimulation of tumor-associated angiogenesis, and metastatic invasion. His group is currently studying the downstream signaling pathways affected by COX-2 derived eicosanoids and has found important crosstalk between the prostaglandin and epidermal growth factor receptor signaling pathways, laying the groundwork for the use of combinations of different inhibitors for cancer treatment and prevention.
One of his lab’s most significant findings is that COX-2 selective inhibitors block colon cancer cells from growing in vitro. In 2000, Ray was part of an international research team that reported in The New England Journal of Medicine that the use of a COX-2 inhibitor led to a significant reduction in the number of polyps in patients with familial adenomatous polyposis, a genetic disorder that leads to the growth of multiple premalignant colon polyps.
From 1996 to 2003, Ray served as Director of the Division of Gastroenterology, Hepatology, and Nutrition at Vanderbilt, expanding the number of faculty in the division, and doubling both research funding and clinical revenue. He also holds the position of Director of the NIH Digestive Disease Research Center (DDRC), which he was instrumental in founding and which is only one of 16 such centers in the US. Wanting to dedicate more time and energy to his DDRC responsibilities and to his primary research program, in late 2003, Ray stepped down from his role as GI division director. “I continue to get very excited when we find out more information about what makes cancer cells different from normal cells, and how we can take advantage of those differences in devising new therapeutic or prevention options,” he explained. Ray also serves on the Board of Scientific Advisors at the National Cancer Institute (NCI), on the advisory committee to the director of the National Institute of Diabetes and Digestive and Kidney Diseases, and on the medical advisory board for the National Colorectal Cancer Research Alliance.
As he notes, “I consider this one of the most exciting, but also one of the most challenging times to be involved in translational research. The unraveling of the human genome has opened up new vistas for scientific investigators—frontiers we can only begin to imagine. As time goes on, I’m sure that more and more researchers will begin to look at their findings in the lab as not just an end in itself, but as a link in the chain to ease the suffering of patients.”
