Cardiovascular Genetic and Genomic Sciences - Division of Cardiovascular Medicine ::

Cardiovascular Genetic and Genomic Sciences

Overview | Physiologic Regulation | Molecular Biology
CATHGEN | The AGENDA Project | Translational Genomics

Cardiovascular Genomic Medicine at Duke: An Overview

Studies in this cutting-edge translational research area range from basic mechanistic approaches to identification of high-risk groups and genomic predictors, to incorporation of genomic tools into daily clinical decision-making.

Highlights of this work are presented in the CV Genomics Forum for discussion every Thursday at 9 a.m. in the CIEMAS 2240 conference room. All are invited; a list of past and future speakers can be found at here.

Genomic Expertise and Biorepositories

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 combination makes Duke a unique place to study and work in CV genomics.

These collaborations involve the university-wide Institute for Genome Sciences & Policy (IGSP), the Division of Cardiovascular Medicine, and a number of other units with special expertise at Duke, including the Center for Human Genetics, the Duke Clinical Research Institute, the Sarah Stedman Center for Nutrition & Metabolism, and the joint Duke-UNC proteomics core (for more information, see the "Facilities" section below).

Further, Duke University Medical Center's 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 the last 6-10 years, provide rare opportunities to incorporate genomic science into clinical medicine.

Unique features of these databases include:

Their robust, standardized phenotypes

Clinical data

Adjudicated events

Outcomes of acute cardiovascular events

High quality DNA, RNA, and serum samples that can used for genome-scale molecular analyses.

Investigators at the IGSP and elsewhere on campus are expert in analysis of large multidimensional data sets derived from these samples and in building integrated predictive models that will facilitate the utilization of genomic information in clinical trials and in clinical practice.

Examples of Databases Include:

CATHGEN (CATHeterization GENetics): Includes data from over 6,000 highly phenotyped cardiology patients who have undergone cardiac catheterization at DUMC since 2001 and are followed for outcomes
EPGEN: A similar database for patients undergoing electrophysiologic procedures implemented in 2006

GENECARD (GENetics of Early onset CARdiovascular Disease): Contains data from more than 900 multigenerational families ascertained for early onset CAD

PEGASUS (Perioperative GEnetic And Safety Study U.S.): Contains data from some 6,500 highly phenotyped cardiac surgery patients with carefully documented short and long-term outcomes recorded)

VascGEN (Vascular Genetics): Highly phenotyped vascular patients with either claudication or chronic limb ischemia

Facilities

The Duke Institute for Genome Sciences & Policy, a campus-wide genome institute under the direction of Huntington Willard, PhD, is built around a series of integrated centers that house intellectual and equipment resources and foster genomic research on campus:

The Center for Genomic Medicine, headed by Geoffrey S. Ginsburg, MD, PhD, enables genomic discovery and clinical studies in cardiovascular medicine and other fields focused on the translation of genetics and genomics into clinical practice.

The Center for Applied Genomics & Technology (CAGT) is a resource and focal point for the development and application of novel approaches for genome analysis. Within CAGT are core facilities for gene expression analysis, high-throughput genotyping, and sample processing.

Duke Center for Human Genetics is an international leader in the study of inherited disorders, and has as its mission the development of gene identification projects through partnerships with clinicians and basic scientists. This center provides a wealth of experience toward understanding the genetic determinants of human disease, and has established core resources to enable and support collaborative research programs. Among these resources is the Molecular Genetics Core for high-throughput genotyping.

Sarah W. Stedman Nutrition & Metabolism Center has developed a research-dedicated metabolomics/biomarker laboratory that conducts metabolic, endocrine, inflammatory marker, and physiologic profiling of cultured cells, animal models, and human subjects. This includes a research-dedicated, mass-spectrometry-based metabolic profiling core facility.

UNC-Duke Michael Hooker Proteomics Center provides researchers with a state-of-the-art facility to identify proteins and to assist in the characterization of protein modification and differential expression from complex biological specimens. This shared facility is a joint operation of the University of North Carolina at Chapel Hill (UNC) and Duke University and Medical Center.

Biosite Inc. is a research-based diagnostics company based in San Diego. Biosite employs propriety technologies for antibody development and engineering, immunoassay development, sample handling, preparation and analysis for the targeted and quantitative analysis of protein analytes from complex biological specimens, and has ongoing collaborations with Duke for development and execution of high throughput protein assays.

Sampling of Duke University Investigators Involved in CV Genomics Projects

Brian Annex (CV medicine) -- Genomics of peripheral vascular diseases and limb preservation

Richard C. Becker (CV medicine, DCRI) -- Genomics and hematology endpoints in CV clinical trials

Vann Bennett (cell biology) -- Ankyrin-B mutations and long-QT syndrome)

Ashley Chi (IGSP) -- Genomics of venous thrombosis

Jamie Cuticchia (IGSP) -- Creation of Web-based clinical data entry supporting CV genomics trials

Mike Dial (and David Seo, Geoff Ginsburg, Debra Schwinn) (CV medicine, IGSP, anesthesiology) -- Duke/UNC proteomics collaboration designed to elucidate novel CV disease biomarkers

Mark P. Donahue (CV medicine) -- Genomics/metabolomics of CAD

Holly Dressman (IGSP) -- IGSP micorarray capabilities for use in CV genomics (and other translational) projects

Pat Dverka (IGSP) -- Policy issues surrounding introducing genomic predictors into clinical medicine

Victor J. Dzau (CV medicine, Chancellor for Health Affairs) -- Physiological genomics and cardiac stem cell therapy

G. Michael Felker (CV medicine, DCRI) -- Genomics of heart failure

Camille Frazier (CV medicine) -- STAGE project

Morton Friedman (biomedical engineering) -- Genomics of CV shear stress

Geoffrey Ginsburg (IGSP, CV medicine) -- IGSP biorepository, discovery and incorporation of genomic predictors into clinical medicine

Christopher B. Granger (cardiology, DCRI) -- CV proteomics and genetic/biomarker predictors in clinical trials

Beth Hauser (CHG) -- Inherited CV disease (statistical genetics approaches)

Patrick M. Hrantizky, MD (CV medicine) -- Genomics/genetics of arrhythmias

Nan Jokerst (engineering) -- Merging genomics, nanotechnology, and microfluidics into sensors

William E. Kraus (CV medicine, CHG) -- Metabolomics of CAD, GENECARD/Offspring study, CATHGEN

Jeffrey H. Lawson (surgery) -- Genomics of peripheral vascular and carotid artery disease

Douglas Marchuk (genetics) -- Using inherited CV disease to predict more mechanisms underlying common complex CV phenotypes

L. Kristin Newby (CV medicine, DCRI) -- CV proteomics and genetic/biomarker predictors in clinical trials

Mark Newman (and Joseph Mathew, Hiliary Grocott) (anesthesiology) -- Genetics of perioperative stroke

Chris Newgard (Stedman Center, pharmacology) -- Metabolomics of CV disease

Christopher M. O'Connor (CV medicine, DCRI) -- Genomics of heart failure

Thomas L. Ortel (hematology) -- Genomics of platelet activation

Mihai V. Podgoreanu (anesthesiology) -- Perioperative genomics and myocardial adverse events

Howard Rockman (and Matt Wolf) (CV medicine) -- Genetics of myocardial hypertrophy; Drosophila as a model for the identification of genes causing adult human heart disease

Debra A. Schwinn (anesthesiology, IGSP, CV medicine) -- Perioperative genomics and postoperative CV outcomes

David M. Seo (CV medicine, IGSP) -- Novel biomarkers of CAD identified via expression profiling in blood and atherosclerotic disease tissues

Svati H. Shah (CV medicine, CHG) -- Genetic predictors of coronary artery disease, pharmacogenomics

For more information on several of these research efforts, please visit the links at the top of this page.