Cardiovascular disease remains the world’s leading cause of death, with heart failure alone afflicting over 26 million people around the globe, and congenital malformations being the most common human birth defect. Despite decades of work, patients and doctors still need scientific and medical breakthroughs to combat these devastating diseases.

To address this critical situation, the Gladstone Institute of Cardiovascular Disease leverages important genetic, developmental, chemical, biological systems, computational, and engineering approaches to study heart disease and stem cell biology.

Recently, much of their work leverages two paradigm-shifting discoveries: induced pluripotent stem cells and CRISPR-Cas9 gene editing. The scientists who discovered these technologies, Shinya Yamanaka and Jennifer Doudna respectively, operate labs at Gladstone. Other Gladstone researchers have also uncovered new and more efficient ways to use these approaches to study cardiovascular disease and transform their findings into therapies that help repair damaged hearts.

Gladstone scientists also train the future generation of cardiovascular physicians and researchers. Learn more about Gladstone’s training programs.

“We bring together MDs and PhDs, stem cell biologists, tissue and genome engineers, and physiologists—all working toward the same goal of better understanding how the heart forms and what can go wrong in this vital organ, so that we can help people with cardiovascular disease.”

Benoit Bruneau, PhD
Director, Gladstone Institute of Cardiovascular Disease

Major Scientific Achievements

Revealed Gene Networks that Control Heart Formation

Gladstone scientists mapped gene networks that direct the development of fetal hearts, unraveling how nature tells a cell to become a heart cell and form an organ. Finding these molecules has profoundly changed our understanding of congenital heart defects, and led to the discovery of the genetic causes of heart disease, paving the way toward preventing these conditions in the future.

Reprogrammed Cells to Regenerate Damaged Hearts

When a heart attack occurs, blood flow is lost to a portion of the heart muscle. As a result, the heart muscle dies and cardiac fibroblasts—which make up about 50 percent of the heart— move in to form non-beating scar tissue. Gladstone investigators reprogrammed fibroblasts in a mouse heart into beating heart muscle. So, instead of forming scar tissue, the fibroblasts became beating cardiomyocytes, incorporated themselves into the heart tissue, and improved pumping of the heart. The approach of harnessing resident cells to regenerate the heart is now being developed toward clinical application within a spin-out company, Tenaya Therapeutics.

Improved Cellular Reprogramming Techniques

The initial discovery that adult cells can be reprogrammed into stem cells by Gladstone Investigator Shinya Yamanaka revolutionized biology, energized research into regenerative medicine, and was recognized with the 2012 Nobel Prize. Gladstone scientists identified small molecules that can replace the genetic material that was traditionally used to reprogram cells, and successfully reprogrammed fibroblasts to pluripotent stem cells using CRISPR-Cas9 technology. They also identified discrete combinations of small molecules that can reprogram fibroblasts directly into heart, neural, liver, and pancreatic cells, simplifying the process of reprogramming to specific cell types.

Discovered Genetic Causes and Underlying Mechanisms of Heart Disease

Since 1979, Gladstone investigators have been at the forefront of heart disease research. Early on, they made significant contributions to our understanding of how cholesterol and apolipoproteins are involved in coronary artery disease. More recently, they shifted their focus to better understand early heart development and birth defects that affect the heart. They discovered genetic causes of human cardiac septal defects and valve disease, and showed how combinations of subtle genetic variation can cause human disease.

Described the Link Between Cholesterol and Heart Disease

Gladstone scientists identified and described the characteristics of apolipoprotein E (apoE) and discovered its involvement in cholesterol metabolism and heart disease. This influential research also laid the basis for showing apoE4’s involvement in Alzheimer’s and other neurological diseases.

Cardiovascular Experts

Director’s Message

We bring together MDs and PhDs, tissue engineers, stem cell biologists, genome engineers, and physiologists—all working toward the same goal of better understanding how the heart forms and what can go wrong in this vital organ, so that we can help people with cardiovascular disease.

“We are pushing our science into areas of untapped potential.”

We believe in the power of interdisciplinary research as a way to achieve something greater together than any of us could on our own. By using the newest technologies, we are pushing our science into areas of untapped potential, which will propel cardiovascular research in new and exciting directions.

Scientific Advisory Board

Brian Black, PhD
Cardiovascular Research Institute
UC San Francisco

George Q. Daley, MD, PhD
Children's Hospital Boston Harvard Medical School
Howard Hughes Medical Institute

Joseph Goldstein, MD
Departments of Molecular Genetics and Internal Medicine
University of Texas Southwestern Medical Center at Dallas

Andrew R. Marks, MD
Helen Wu Center for Molecular Cardiology
Columbia University College of Physicians & Surgeons

Deborah Nickerson, PhD
Professor of Genome Sciences
University of Washington School of Medicine

Eric N. Olson, PhD
Department of Molecular Biology
University of Texas Southwestern Medical Center at Dallas

Marlene Rabinovitch, MD
Department of Pediatrics, Cardiology
Stanford Cardiovascular Institute
Stanford University School of Medicine

Janet Rossant, PhD
Developmental and Stem Cell Biology Program
The Hospital for Sick Children, Toronto University of Toronto

Christine Seidman, MD
Department of Genetics and Medicine Harvard Medical School

Irving L. Weissman, MD
Institute for Stem Cell Biology and Regenerative Medicine
Stanford University School of Medicine

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