Program Leader: Richard Lee, MD

Click here to download the HSCI Cardiovascular Disease Program Overview.

To watch a video about the program, click here.

Background

Even though medical science has made great progress in preventing and treating heart disease in the past decade, one American dies from cardiovascular disease every 38 seconds, making heart disease the leading cause of morbidity and mortality in the U.S. This will soon be a worldwide epidemic, as the rate of heart disease increases in India, China and other countries. Some people associate cardiovascular disease with the elderly, but over 151,000 Americans under the age of 65 die of cardiovascular disease every year.

Heart failure is usually caused by the death of heart muscle cells from a heart attack. Around a third of heart attacks are “silent”, because they don’t cause symptoms. However, the heart is still damaged and can fail later. Our current therapies for heart failure slow the progression of the disease, but injury to heart muscle is generally cumulative and irreversible. Even with our best therapies, the survival rate from heart failure is worse than many metastatic cancers. At present, we can only delay the progression of the disease, but we can’t stop it. For a few patients, heart transplantation is an option, but for most people living with heart disease, their best hope is for scientific research to discover new ways to restore heart function. 

Focus

The heart was long assumed to have little ability to regenerate on its own. In just the past few years, many research groups, including several in HSCI, have discovered cells in the heart that can restore heart function. Our challenge is to develop practical ways to harness this ability to generate new heart cells and turn it into an effective therapy. The HSCI Cardiovascular Program aims at achieving this through collaborative and complementary projects.

Sample Projects

One collaboration aims to define key factors limiting human heart regeneration. Fish (zebrafish) can easily regenerate injured myocardium, while humans and other mammals have very limited cardiac regeneration potential. The cardiac cells (cardiomyocytes) of adult zebrafish are able to dedifferentiate, divide into multiple cells, and replace damaged cardiac tissue. The plan is to translate this information into new therapies that either generate new muscle cells for the heart or drive the human heart to regenerate its own muscle cells.

The goal of a second collaboration is to repair the damaged heart through guided differentiation of progenitor cells. Attaining this goal requires the characterization, amplification, and directed differentiation of tissue-specific progenitors. Fundamental in this process is to understand the molecular network that defines the various developmental stages of cardiomyocyte progenitor specification and differentiation (“cardiogenesis”). The ability to change the transcriptional circuits with defined transcription factors or epigenetic modifications will allow scientists to reprogram cells, conferring pluripotency on somatic cells, or trans-differentiation between “terminally” differentiated cell states. For cardiac regeneration, it will be desirable to guide endogenous or exogenous progenitors towards differentiated cardiomyocytes.

Extending the Program

The Cardiovascular Program comprises numerous junior and senior investigators working collaboratively on regenerating myocardium and treating heart failure. One way to faster research in this group has been to share experimental approaches, technologies and reagents, which has also led to the creation of new collaborations across HSCI laboratories.