Cardiovascular genomics is a cutting edge translational research area at Duke. Studies range from basic mechanistic approaches to the identification of high-risk groups and genomic predictors, to incorporation of genomic tools into daily clinical decision-making. Unique biorepositories and expertise are available across the medical center and university, with strong interdisciplinary synergism facilitating studies that are not possible in other settings.
This depends on close collaborations between the IGSP, the Division of Cardiovascular Medicine, and a number of other units, including the Center for Human Genetics, the Duke Clinical Research Institute and the Sarah Stedman Center for Nutrition & Metabolism. Duke University Medical Center also maintains unique databases of highly phenotyped individuals with cardiovascular disease in outpatient, inpatient, and perioperative settings, whose clinical data and blood has been collected prospectively over many years, providing rare opportunities to incorporate genomic science into clinical medicine. The uniqueness of these resources cannot be overemphasized due to their robust, standardized phenotypes, clinical data, adjudicated events, and outcomes of acute cardiovascular events along with high quality DNA, RNA and serum samples that can used for genome scale molecular analyses.
Geoffrey S. Ginsburg, M.D., Ph.D. is the Director for Genomic Medicine in the Duke Institute for Genome Sciences & Policy. He is also Professor of Medicine and of Pathology at Duke University Medical Center. His research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
Svati H. Shah, MD, MHS, is an Assistant Professor of Medicine in the Division of Cardiology, Department of Medicine. Her research focuses on genetic epidemiology and gene-environment interactions in complex cardiovascular diseases, including dyslipidemia, premature coronary artery disease, aortic stenosis, and peripheral vascular disease.
Deepak Voora, MD, is an Associate Investigator in the IGSP and an Instructor of Medicine in the Division of Cardiology. Dr. Voora's research interests lie in the area of cardiovascular pharmacogenetics. Using a broad array of genomic technologies from genotyping, resequencing, gene expression, and metabolomics he probes the response to a variety of cardiovascular medications.
Predicting Response and Resistance to Cardiovascular Therapies:
The goal of these studies is to utilize genetic and genomic tools to develop robust pharmacogenomic predictors of response and adverse events for medications used to treat cardiovascular disease. One series of studies with Deepak Voora, MD, and Svati Shah, MD, utilizes a SNP based approach in the STRENGTH cohort to develop of predictors of response and adverse events to 'statins' – cholesterol-lowering agents.
Deepak Voora, MD, is also leading a study of aspirin resistance using both the peripheral blood and platelet transcriptomes and serum proteomics to develop novel signatures predictive of the effects of this important cardiovascular therapeutic. The work is taking place within the The Duke Clinical Research Unit (https://dtmi-plone.dcri.duke.edu/about-us/organization/duke-clinical-research-unit), a state-of-the-art research facility located within the Duke University Medical Center campus that provides infrastructure support for identifying and validating novel biomarkers. This study is now supported by an NIGMS Challenge Grant (1RC1-GM091083-01, Geoff Ginsburg MD, PhD, PI).
Predicting near-term events in acute coronary syndromes:
Supported in part by the MURDOCK Gift Fund, the goal of these studies is to develop novel clinical/molecular risk predictors that will detect individuals at high risk for developing an acute coronary syndrome within one year -- in other words, to detect “the vulnerable patient.” Within Duke's unique CATHGEN resource (developed by Drs William Kraus and Chris Granger) we have identified a series of patients who were stable during their index catheterization yet who went on to develop ACS within one year. The hypothesis is that genomic and molecular analyses of blood based biospecimens from these patients will yield a novel multi-dimensional risk predictor for the near term event.
Deepak Voora
deepak.voora@duke.edu
919.684.6266
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