by Hannah Buckelew

Rajasekaran Namakkal-Soorappan, Ph.D., an associate professor in the Department of Pathology’s Division of Molecular and Cellular Pathology, has been awarded a Transformative Project Award from the American Heart Association for his project, “Atrial Remodeling Precedes Ventricular Dysfunction in Proteotoxic Cardiac Disease.” This $300,000 award will run for three years, through 2026.

The atrial chamber, consisting of the left and right atrium, is responsible for pumping and receiving blood and maintaining efficient circulation of blood throughout the body. In the event of rhythm disturbances in the heart, or arrhythmia, pacemakers may be used to send electrical pulses to restore normal rhythm.

Aside from traditional factors that are known to cause rhythm disturbances, Namakkal-Soorappan’s recent studies have demonstrated proteotoxicity, an additional factor affecting atrial function. Proteotoxicity refers to the toxic effects that arise from the accumulation of incorrectly folded or unfolded proteins that form stable aggregates within cells. Protein folding can be caused by genetic mutations, environmental factors, or aging processes. If left unchecked, these abnormal protein deposits can disrupt the normal heart rhythm and ultimately contribute to atrial fibrillation (AFib). Timely treatment can preserve cardiac rhythm and prevent AFib and atrioventricular complications, including functional and structural defects.

Namakkal-Soorappan’s team will investigate the susceptibility of the atrial electrical conduction system (ECS) to proteotoxic insults in triggering atrial remodeling, which impairs functionality in pacemakers and leads to ventricular remodeling and dysfunction, and heart failure. The lab will investigate whether protecting the ECS from proteotoxic remodeling can preserve its function and prevent ventricular remodeling. The team will test this hypothesis by studying age-dependent changes in electrical conduction and atrial remodeling in a mouse model of human proteotoxic cardiomyopathy.

“We are hopeful this study will lead to the development of appropriate therapy to prevent toxic protein aggregates in humans,” says Namakkal-Soorappan. “This research will aid in enhancing current programs in cardiac research.”