The University of Virginia (UVA) has a long and illustrious history for outstanding Cardiovascular Research. Notable research began with the work of Eugene Landis in the Department of Medicine in the late 1920’s. Faculty members in multiple Departments and Divisions at UVA continued the tradition of cardiovascular research over the years, including making major contributions to the study of arterial mechanics and valve replacement; transplant; cardiac imaging; and electrophysiology. In the early 1960’s two basic science Departments, Physiology and Pharmacology, recruited several outstanding faculty members who greatly strengthened cardiovascular research at UVA. Most notable, was Dr. Robert M. Berne who had conducted highly innovative studies suggesting that the metabolic by-product adenosine plays a key role in the control of blood flow to the heart. Indeed this work established a major area of focus for study in his lab and many others over a period of decades following his recruitment in 1968 as the Chair of the Physiology Department. His charge was to be part of a major initiative in developing basic medical research at UVA. With quiet strength and gentle leadership, he built one of the premier physiology departments in the world, serving as the Charles M. Slaughter Professor of Physiology for the next 26 years. In 1994 he became Emeritus Professor of Physiology, where he continued writing and providing his expertise, until his death in October 2001.
Dr. Berne’s research led to adenosine being recognized as a molecule with wide ranging biological importance, and this provided a focus for research by hundreds of investigators throughout the world over the past several decades. In the 1980’s and the 1990’s his work on adenosine took on new life with the recognition that, in addition to its role in regulation of cardiac blood flow, the molecule plays a key role in the control of a multitude of biological processes. For example, a fellow in the laboratory, Luiz Bellardinelli, worked with Dr. Berne’s group to discover that adenosine plays a key role in regulating heart rhythms. This discovery led directly to a patent for a clinical application for adenosine as Adenocard, and widespread use of the drug throughout the world.
Dr. Berne’s research and teaching yielded more than 200 scientific articles and three textbooks authored with Matthew Levy that have been used widely by Medical Schools throughout the world. In the process of building the department and research programs, he trained dozens of graduate students and post-doctoral fellows, who later populated the academic community with senior professors and chairs of departments. In addition, his unflagging support of the other faculty in the department helped many of them to rise to prominence as well.
The huge impact of Dr. Berne’s work was recognized in many ways. He was the President of the American Physiological Society in 1972, elected to the Institute of Medicine of the National Academy of Science in 1979, received the Gold Heart award of the American Heart Association in 1985, and was elected to the National Academy of Science in 1988.
Dr. Berne led efforts to establish our Cardiovascular Research Training Program in 1977, and secured competitive NIH funding. Indeed, this grant was renewed recently by Drs. Owens and Duling and is one of the largest and longest running training grants in NHLBI or NIH history with 44 years of continuous funding. Indeed, our Cardiovascular Training Program is widely regarded as one of the best in the country. With over 55 faculty mentors in more than 10 departments, we have an outstanding record of biomedical research training and our CVRC members and former trainees have contributed to our fundamental understanding of basic cardiovascular function, as well as a leadership role in developing innovative new treatments and therapies. Our faculty members and their trainees are using state-of-the-art experimental approaches to address some of the most important problems in medical science.
Major areas of current research strength within the CVRC include: vascular development, angiogenesis, arteriogenesis, vascular patterning/remodeling, endothelial cell biology, smooth muscle biology, inflammation, immunology, macrophage function, atherosclerosis, aneurysms, diabetes, sickle cell anemia, ischemia re-perfusion injury, cardiovascular imaging, adhesion molecule biology, epigenetic control of gene expression in development and disease, heart failure, systems biology, stem cell biology/therapeutics, targeted drug delivery, and vascular hemodynamics.
In the early 1990’s, it became evident that a multidisciplinary approach would be necessary to maintain a competitive position in cardiovascular research and training. It was determined that a center of excellence in Cardiovascular Research should be established, and under Dr. Berne’s leadership and initiative, major portions of the royalties from his patents were returned to the University of Virginia, and used to establish and endow the Cardiovascular Research Center.
In recognition of that fact, the Dean of the School of Medicine Dr. Robert Carey, approved the creation of the Robert M. Berne Cardiovascular Research Center (CVRC) at the University of Virginia in November of 1992, and Dr. Brian R. Duling was named its first director and chair-holder.
Brian R. Duling received his Ph.D. in physiology from the University of Iowa in 1967. After a post-doctoral fellowship with Dr. Berne, he began his career at UVA in 1968, as an instructor of physiology. Since then he has served in a variety of capacities within the University, including acting Chair (1980) and Vice-Chair (1984-1991) of the Department of Physiology, founding director of the Robert M. Berne Cardiovascular Research Center (1992-2002), Robert M. Berne Chair (1992-2011), and Associate Dean for Graduate Studies (2008-2010). Dr. Duling has been a world-class cardiovascular scientist at the University for several decades. With the use of the microscope in the investigation of the small blood vessels that control blood flow, his laboratory established a co-culture system of endothelial and smooth muscle cells that allowed elucidation of the vital interactions that occur between these two cells. This novel research has had important implications for our overall understanding of the cardiovascular system, as well as associated problems such as hypertension. His classroom activities included the teaching of renal, cardiovascular, and respiratory physiology to medical students, and a variety of graduate courses on the microcirculation and on vascular biology.
Dr. Duling has been honored with a number of prestigious awards over his career—both for teaching and research—including the Robert Bennett Bean Teaching Award, the Philip Dow Award, the Philip Bard Award, the AHA Brown Award, the Eugene Landis Award, the Wiggers Award, an NIH MERIT Award, the Abbott and Malpighi Awards from the European Society for Microcirculation, the UVA Medical Student Teaching Award, UVA’s Academy of Distinguished Educators Award, the Zweifach Award, APS’ Mentor of the Year Award, UVA’s Distinguished Scientist Award. He also has served as president of the Microcirculatory Society and the American Physiological Society and has been provided countless Lectures and Fellowships. Dr. Duling was continuously funded by the National Institutes of Health throughout his career, and has brought in tens of millions in research support to UVA. He has published approximately 186 articles in leading physiology journals, many of which are highly cited. Some of Duling’s early, ground-breaking work in the field is frequently cited today, more than forty years after publication.
Dr. Klaus Ley served as Co-Director of the CVRC beginning in 2001 and then served as CVRC Director from 2002 until his leaving UVA in 2007 to accept a position at the La Jolla Institute for Allergy and Immunology as Head of the Division of Inflammation Biology. Dr. Ley joined UVA in 1994 as a Professor in the Department of Biomedical Engineering and Molecular Physiology and oversaw a large lab, graduating over a dozen doctoral candi¬dates.
Dr. Ley holds a MD and completed postdoctoral training in physiology and biomedical engineering in Berlin and at the University of California – San Diego. He has worked in the field of white blood cell adhesion for nearly 20 years. He published more than 200 scientific papers and is co-founder of Targeson, a biotech company developing contrast agents for molecular imaging. The physiological and biomechanical principles of his studies underlie some of Targeson’s novel site-targeted adhesive technology. Dr. Ley received more than $12 million in NIH grants during his time as Director. Dr. Ley was extensively involved in facilitating and supporting research that can be translated into therapies and improve patient care.
During his time at UVA, Dr. Ley helped to pioneer the field of vascular immunology and is internationally recognized as a leader in the field. In 2010 he was awarded the prestigious Malpighi Medal at the World Congress for Microcirculation in Paris, France. He has received many major awards, including the prestigious Marie T. Bonazinga Research Award, the highest honor presented by the Society for Leukocyte Biology. Dr. Ley was directly responsible for expanding the CVRC’s vascular inflammation focus and built partnerships and collaborations that expanded the membership of the CVRC to over 100 members. Dr. Ley continues to hold an adjunct BME appointment and is still a collaborative member of the CVRC.
In 2007, Dr. Gary Owens was appointed as the new Director of the CVRC. Dr. Owens is a Professor of Molecular Physiology and Biological Physics and has been on the faculty since 1982, when he was hired by Dr. Berne. He received his M.S. and Ph.D. degrees at the Pennsylvania State University and completed post-doctoral training in the Department of Pathology at the University of Washington. He was the Associate Dean for Graduate Education at UVA from 1988-2007, and lead efforts to reorganize our School of Medicine graduate programs into the Biomedical Sciences (BIMS) administrative structure in 2003. He has served as Director of our highly ranked MD/PhD Program (MSTP) since 1998, having taken over a struggling program that had lost its NIH funding, and has built it into one of the highest ranked programs in the country. He is the past President of the North American Vascular Biology Organization, the largest Vascular Biology Society in the World. He also chaired the 2003 Vascular Biology Gordon Conference. He has chaired and served on numerous Review Committees of the NIH and the AHA, including serving as Chair of the Cell Biology Study Section, the NHLBI Program Project Review Committee, and the NHLBI Board of Scientific Councilors which is responsible for reviewing all intramural research programs in the NHLBI for the Institute Director. He was also one of only three scientists who served on an NIH Re-Invention Committee organized by the NIH Director Hal Varmus (Nobel Laureate and current NCI Director) charged with doing a major re-structuring of the NIH in 1993-1999 that contributed significantly to the eventual doubling of the NIH budget and dramatically altered the grant review process. He served as the Co-Editor of the Journal of Vascular Research. He was the recipient of the 1988 Bowditch Award of the American Physiological Society which is the top award of that >30,000 member Society for an investigator under the age of 40, was the 2004 Robert M. Berne Lecturer of the American Physiological Society, and is an NIH MERIT Award recipient. He was chosen to give the prestigious AHA Russell Ross Memorial Lecture in 2008. He is primary inventor on numerous patents, including those that were part of his UVA startup company, Setagon, Inc. that developed a novel nanoporous drug eluting stent technology. Setagon was purchased by Medtronic in 2007 who is further developing the Setagon drug elution technology for clinical applications.
Dr. Owens is internationally renowned for his studies of molecular and epigenetic control of SMC differentiation during embryonic development as well as phenotypic switching in vascular disease. He has published over 150 original peer reviewed papers in the field, and numerous reviews on vascular smooth muscle cell (SMC) differentiation, including two Physiological Reviews that are among the most highly cited reviews in the field. His original research paper, Geisterfer, Peach, and Owens in Circulation Research in 1988 http://www.ncbi.nlm.nih.gov/pubmed/3280155?dopt=Citation , which was the first paper to show that the contractile agonist angiotensin II also has growth promoting properties, has been cited over 1000 times. His h-index rating is currently 59 (the average for newly elected members of the National Academy is 45). His lab has pioneered studies of molecular and epigenetic mechanisms that control activation of SMC marker genes during development, and how these processes are altered during phenotypic switching of SMC in response to vascular injury, or in disease states such as atherosclerosis. A major strength of his studies is that they continually seek to validate results obtained in vitro in cultured SMC using sophisticated in vivo model systems.
Dr. Owens has trained over 40 pre- and post-doctoral fellows including six former MD/PhD students, nearly all whom have gone onto highly successful careers in academia and industry, including three current or former UVA SOM faculty members: Drs. Wamhoff, Ailawadi, and McNamara. Dr. Owens is currently Principal Investigator on three NIH R01 research grants, our NIH MSTP training grant, the NIH Cardiovascular Training Grant, and an R25 undergraduate URM training grant that supports our Summer Research Internship Program or SRIP (a program he started in 1992). He is also PI on our UVA-AstraZeneca Alliance grant, which has greatly fostered translational and clinical research and training within the CVRC. In total these grants bring in approximately $5M in annual funding to UVA.
In summary, the CVRC has attained and maintained the highest level of national and international recognition and an enviable funding record since being created 20 years ago. Researchers within the CVRC have an outstanding record of securing extramural research funding from the NIH, industry, and AHA. Prior program project (PPG) and bioengineering research partnership (BRP) grants include the study of vascular smooth muscle; pulmonary injury; atherosclerotic-resistant endothelium; and diabetic vascular disease. Currently we have a PPG studying immune cells in atherosclerosis and vascular disease and a BRP studying leukocytes and molecular imaging agents. The CVRC now recognizes 110+ faculty members who have an interest in cardiovascular research of which 51 are approved PhD mentors on our NIH CVTG. The CVRC is positioned to continue to foster outstanding basic, translational, and clinical CV research at UVA.