As president of the American Heart Association (AHA), Joseph C. Wu, MD, PhD is at the forefront of the latest research in heart and vascular care. Dr. Wu is the director of the Stanford Cardiovascular Institute (CVI). He is also the Simon H. Stertzer, MD, Professor of Medicine (Cardiology) and Radiology at Stanford University School of Medicine.
Dr. Wu began his term as AHA president in July 2023. He has since combined his vast expertise in stem cell technology, clinical genomics, and precision medicine to advance several promising discoveries. Through his revolutionary work, Dr. Wu is developing groundbreaking techniques to predict, prevent, and treat cardiovascular disease. His research lays the groundwork for future innovations in precision medicine and personalized care.
“Clinical trial in a dish” revolutionizes research
Human induced pluripotent stem cells (iPSCs) are key components of Dr. Wu’s work. Through a concept he calls “clinical trial in a dish,” Dr. Wu and his team use iPSCs to gain a better understanding of cardiovascular diseases and accelerate the discovery of effective drugs to treat them.
Dr. Wu and his team at the Stanford Medicine-Joseph Wu Lab create iPSCs using donated skin or blood cells from thousands of patients. In the lab, Dr. Wu and his team reprogram the stem cells, essentially “resetting” them to their embryonic stage. This process enables the iPSCs to develop into many different cell types.
Dr. Wu’s team specializes in differentiating iPSCs into components that make up a human heart. These components include cardiomyocytes, cardiac fibroblasts, endothelial cells, smooth muscle cells, and pericytes. The cells have the unique advantage of being genetically matched to the patients.
Using patient-specific iPSCs, Dr. Wu and his colleagues study the genetic, molecular, and pathological mechanisms of heart and vascular diseases. Dr. Wu and his team test a variety of medications — including new drugs and those that have been FDA approved — on iPSCs in the lab. These tests allow Dr. Wu to determine which drugs are effective at treating certain diseases without the inherent risk of side effects involved with clinical trials in humans.
Integrating technologies to advance precision medicine
Clinical trial in a dish is paving the way for novel discoveries by altering the landscape of precision medicine. At the Stanford CVI, Dr. Wu and his team are merging stem cell technology, clinical genomics, and the powerful gene-editing tool CRISPR to prevent and cure diseases with unprecedented accuracy.
Dr. Wu combines these technologies to elucidate how certain genetic mutations cause cardiovascular diseases, including genetic cardiomyopathy, cardiac arrhythmias, and vascular diseases. By integrating these innovations, Dr. Wu and his team can:
- Identify the gene mutation responsible for the defect that causes these life-threatening disorders
- Determine the most effective medications to treat the disease
- Screen at-risk patients for the genetic mutation to prevent devastating outcomes, such as heart failure and sudden cardiac death
“I believe this is the holy grail of precision cardiovascular medicine,” says Dr. Wu. “I hope that in the upcoming decades, work like this will be a common part of our toolboxes to discover new cardiovascular treatments.”
Collaboration drives innovation
“The more we help one another, the more we help ourselves, our current patients, and future generations,” says Dr. Wu. “Only by uniting our efforts will we make the biggest advances in preventing and treating heart diseases.”
Over the last decade, the CVI team has built a biobank of iPSC lines from more than 2,000 patients. They have shared many of these cells, reagents, and protocols with hundreds of scientific colleagues at institutions all over the nation and the world. “I believe sharing resources is important for science and medicine to advance,” says Dr. Wu.
The HECTOR trial evaluates new treatments for heart failure
For decades, Dr. Wu has pioneered groundbreaking research at Stanford Medicine. Currently, he is the principal investigator for a clinical trial that studies the use of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) to prevent heart failure and treat patients with the condition.
The trial is called “Human Embryonic Stem Cell-Derived Cardiomyocytes in PaTients with ChrOnic Ischemic Left VentRicular Dysfunction Secondary to Myocardial Infarction (HECTOR).” The study focuses on patients who are at risk of heart failure from chronic ischemic cardiomyopathy.
It is the first in-human study in the U.S. that evaluates the use of hESC-CMs to treat heart failure. The HECTOR trial reflects Dr. Wu’s passion for discovering breakthrough treatments and his commitment to shaping the future of cardiovascular care.
Learn more about Dr. Wu’s vision for cellular therapy and precision medicine.
