(NEW YORK, NY, Nov. 18, 2012) – Columbia University Medical Center (CUMC) presented the 2012 Naomi Berrie Award to Christophe Benoist, MD, PhD, and Diane Mathis, PhD, both of Harvard Medical School, for their contributions to expanding understanding of the disease mechanisms underlying type 1 diabetes over the past three decades. The award, given annually by CUMC's Naomi Berrie Diabetes Center, is Columbia's top honor for excellence in diabetes research.
The awards ceremony took place at the 14th annual Frontiers in Diabetes Research Conference on November 17, 2012, in the Russ Berrie Medical Science Pavilion at Columbia University Medical Center.
Type 1 diabetes is caused by the death of insulin-producing beta cells in the pancreas. A major question has been what triggers the immune system to attack and destroy beta cells, and what aspects of the immune system foster or inhibit the attack. Drs. Benoist and Mathis were honored for their work on elucidating these fundamental issues, particularly the mechanisms by which T cells become primed to attack the beta cells.
"Drs. Benoist and Mathis have provided important insights into the basic immunobiology of T cells as they relate to type 1 diabetes," said Rudolph L. Leibel, MD, the Christopher J. Murphy Professor of Diabetes Research, co-director of the Naomi Berrie Diabetes Center at CUMC, and chair of the selection committee. "These issues are of critical importance because understanding them may allow us to prevent type 1 diabetes through immunization and to reverse it in people who have the disease, by interfering with the immune responses that have gone awry."
Many of the discoveries made by Drs. Benoist and Mathis were made possible by their development of a transgenic mouse model that allowed them to study the maturation and fate of T cells in diabetes. This model, unique at the time (early 1990s), is still used in scores of other laboratories to explore the disease mechanisms of autoimmune diabetes. With this mouse, Drs. Benoist and Mathis uncovered the central importance of T cells in ordering the destruction of the beta cells, where these T cells develop, and why they are not destroyed in mouse models of type 1 diabetes.
Their work also is credited with reawakening researchers' interest in central (thymic) tolerance, the mechanism by which newly developed T cells learn to tolerate the animal's own cells and tissues ("self") and distinguish them from foreign invaders ("non-self"). Their studies on the AIRE protein and its control of tolerance—and its role in autoimmune diseases such as type 1 diabetes—is one of their critical contributions. Having uncovered the role of AIRE and the thymus in the normal development of tolerance to the pancreas and other organs, researchers now hope to learn why T cells fail to develop tolerance to beta cells in type 1 diabetes and how this failure can be reversed.
In more recent work, Drs. Benoist and Mathis have teamed with colleagues at Harvard to develop a non-invasive method to image in real-time the development of type 1 diabetes in the pancreas, by following the infiltration of the pancreas by macrophages. The technique is being explored both as a diagnostic aid and as a therapeutic biomarker to gauge the effectiveness of therapies designed to slow the attack.
Drs. Benoist and Mathis have also pioneered the study of "immunometabolism," an emerging field that explores connections between the immune system and metabolism. Interest in the field is fueled in part by the increasing rates of obesity and the role of obesity in inducing inflammation, type 2 diabetes, and other chronic diseases. They identified a microbe, segmented filamentous bacteria, which can block the development of diabetes in a mouse model. They have found that intestinal microbes may also play a role.
Drs. Benoist and Mathis are both faculty of the Department of Microbiology and Immunobiology at Harvard Medical School, and members of the National Academy of Sciences.
"This is the first time that this award has been presented to two investigators simultaneously," said Dr. Leibel. "The selection of these long-standing collaborators recognizes their major insights into the mechanisms by which T cells assault insulin-producing cells in the pancreas and cause type 1 diabetes."
Hongxia Ren, PhD, the junior award recipient, is an associate research scientist in the laboratory of Domenico Accili, MD in the Naomi Berrie Diabetes Center. Based on her discovery that the gene Gpr17 acts as a nutrient sensor and appetite regulator, Dr. Ren is currently examining the hypothesis that signaling activity of Gpr17 in AgRP, neurons in the hypothalamus that are critical for initiating food intake and maintaining energy homeostasis, are involved in regulating satiety and metabolism. If this hypothesis is correct, specific G-protein-coupled receptors could provide therapeutic targets in the treatment of obesity and its comorbidities. She is also exploring the role of liver/central nervous system interactions in the pathogenesis of diabetes.
Established by the Russell Berrie Foundation in 2000, the Naomi Berrie Award for Outstanding Achievement in Diabetes Research promotes and rewards outstanding achievement in the field, while supporting the careers of promising young diabetes investigators. Each year, the recipient—a senior scientist outside Columbia who has made major contributions to diabetes research—is given $100,000 to support a two-year research fellowship for a student or research fellow in his or her laboratory. This year Drs. Benoist and Mathis will share this prize. The second $100,000 award supports a research fellow at Columbia.
Past recipients of the Naomi Berrie Award for Outstanding Achievement in Diabetes Research are Graeme Bell, PhD, University of Chicago (2000); C. Ronald Kahn, MD, Joslin Diabetes Center and Harvard Medical School, (2001); Clifton Bogardus III, MD, National Institute of Diabetes & Digestive & Kidney Diseases (2002); George S. Eisenbarth, MD, PhD, the University of Colorado Health Sciences Center (2003); Douglas Melton, Ph.D. of Harvard University (2004), Michael Brownlee, MD, Albert Einstein College of Medicine (2005); and Michael Schwartz, MD, University of Washington (2006) and Gerald I. Shulman, MD, PhD, Yale University (2007); Bruce Spiegelman, PhD, Harvard University (2008); Richard Nathan Bergman, PhD, University of Southern California; Gökhan S. Hotamisligil, MD, PhD, Harvard University School of Public Health (2010); and Barry E. Levin, MD, University of Medicine & Dentistry of New Jersey (2011).
Upon its official opening in October 1998, the Naomi Berrie Diabetes Center at Columbia University Medical Center established a new standard of care for the 1.6 million people with diabetes in the New York area—combining world-class diabetes research and education programs with unprecedented family-oriented patient care. Founded with support from the Russell Berrie Foundation and other friends, and named in honor of the mother of the late Russell Berrie, founder of RUSS™ Toys, the center is today recognized as the most comprehensive diabetes research and treatment center in the tri-state region and has been designated a national "Diabetes Center of Excellence" – one of only three in the state of New York. Approximately one hundred faculty and students, affiliated with the Center, conduct basic and clinical research related to the pathogenesis and treatment of all forms of diabetes and its complications. For more information, visit http://www.nbdiabetes.org/.
Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research; in medical and health sciences education; and in patient care. The Medical Center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the MD degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest in the United States. For more information, please visit www.cumc.columbia.edu.
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