Laboratory of Cardiac Metabolism
The Laboratory of Cardiac Metabolism examines basic mechanisms of cardiac cell death and survival that can help enlighten the processes underway during myocardial ischemia, loss of cardiomyocytes during aging, heart failure, and diabetic cardiomyopathy. The 2005 cardiovascular statistics from the American Heart Association estimates that over 70 million Americans have some form of cardiovascular disease. Of these, 13 million have coronary artery disease; almost five million with congestive heart failure, and almost 14 million carry a diagnosis of diabetes. Another 5,000,000 are undiagnosed and are at risk of developing significant cardiovascular disease. Saul Powell, PhD, and his colleagues focus on the mechanism of cardiac contractile failure and cardiomyocyte death in the presence of increased oxidative stress. They have demonstrated increased production of oxidative species with downstream formation of protein oxidation products in such diverse pathologies as cardiac ischemia, diabetes, and aging. Ongoing studies are examining the role of the proteasome in cardiomyocyte cell death and/or survival following cardiac ischemia. Whether a cardiomyocyte (or any other cardiac cell) remains viable after ischemia may depend on the relative degrees of inhibition of this proteolytic complex that the investigators are studying.
Every cell is equipped with machinery that removes proteins that are damaged and Powell and his colleagues are interested in knowing how this protein clean-up factory works during myocardial ischemia. The proteasome is a very large molecular structure that consists of multiple sub-units and its job is to break down or degrade proteins. The proteasome is in the nucleus and cytoplasm of every cell and it gets its cues from a cellular substance called ubiquitin that tags a protein that needs to be degraded. From there, the proteasome collects the protein and cuts off the ubiquitin so it can be reused. The proteasome unfolds the protein and feeds it into a catalytic chamber where it is broken down into peptides. Sometimes the peptides will be repackaged and transported back to the cell surface as HLA antigens. These antigens are important for immune system responses. Dr. Powell and his colleagues believe that the proteasome is critical to what goes on in the cell and could help explain how diseases unfold in the human body. They are finding that when proteasomes are not doing their job right, proteins can abnormally accumulate and cause damage. They are working on genetic models that increase proteasome in the cell to figure out how it works in health and in disease.
Lab Members
Name: Andras Divald, PhD
Position: Assistant Investigator
Research: Studies the role of the proteasome in the ischemic heart.
E-mail: adivald@lij.edu
Name: Ping Wang
Position: Senior Research Assistant
Research: Research: Studies proteasome activity in the heart.
E-mail: pwang@lij.edu