Genetically Modified Protein May Bridge Gap In Studying Effectiveness Of Anti-Clotting Drugs
NEW YORK, (Dec. 18, 2007) – Findings published in Nature Biotechnology by Columbia University Medical Center researcher Thomas Diacovo, M.D., may lead to the identification of a research model that will better enable the study of drug therapies to prevent blood clotting in heart attack and stroke patients.
Thomas Diacovo, M.D. Dr. Diacovo, recipient of Columbia’s 2007 Katz Prize in Cardiovascular Research, genetically modified a protein that promotes blood clots in human arteries, so that the same protein could be studied in mice, whose natural biological make-up did not, until now, support the formation of clots with human platelets.
The novel biological platform is the first to allow the in vivo clotting of human platelets in mice, using the protein VWF (von Willebrand Factor), and has yielded a ground-breaking research tool with the help of one of Dr. Diacovo’s research scientists, Jianchun Chen.
Mice possessing this “humanized” form of VWF will be used by those seeking development of anti-clotting drugs to relieve the blockage that occurs in arteries supplying blood to the heart or brain during heart attacks and stroke.
The adhesive properties of VWF in clot formation are tightly regulated such that it preferentially binds to platelets only when immobilized at sites of vascular injury and under hydrodynamic conditions encountered in arteries.
Many therapies fail in clinical trials because models to test drugs prior to human administration can be limited. To this point, several drugs designed to work against human blood platelets could not be adequately studied because mice did not possess the genetically modified protein that facilitated the clotting of human platelets.
“The development of this platform is expected to increase researchers’ understanding of the ability of human platelets to form thrombi at sites of vascular injury in mice,” Dr. Diacovo said of the findings, published this week.
Dr. Diacovo, assistant professor of pediatrics and pathology and director of research for the neonatology and critical care medicine divisions within the Department of Pediatrics at the College of Physicians and Surgeons, was recruited to Columbia University Medical Center in 2005. He received his postdoctoral training in the field of cell adhesion at the Center for Blood Research at Harvard Medical School. Dr. Diacovo is also a recipient of the 2007 Faculty Development Grant awarded by the New York State Foundation for Science, Technology and Innovation, which is given to individuals who show great promise in developing novel technologies for real world applications.
-###-
Columbia University Medical Center provides international leadership in 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, nurses, dentists, and public health professionals at the College of Physicians & Surgeons, the College of Dental Medicine, the School of Nursing, the Mailman School of Public Health, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. www.cumc.columbia.edu