Edwin L. Aguirre
Sudden cardiac arrest is the leading cause of death of young athletes who die while competing or training. According to an article published in the Journal of Athletic Training
, approximately one young athlete dies without warning every three days in the United States.
An interdisciplinary team of researchers led by Moore is studying HCM, which is a genetic disorder that causes the walls of the heart to thicken and become stiff. The condition reduces the heart’s ability to pump blood, which can lead to irregular heartbeats and heart failure. While HCM can occur at any age, there may be no symptoms in children and young adults with this condition, and the disease often goes undiagnosed.
The study, which is being funded by a four-year grant totaling $1.6 million from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH), aims to examine the disease process in great detail – from chemical changes and interactions at the molecular level to the structural arrangement of cardiac muscle fibers at the tissue level.
Moore is the project’s principal investigator (PI). His co-PIs include Prof. William Lehman from the Boston University School of Medicine and Assoc. Prof. Stuart Campbell from the Yale School of Engineering and Applied Science.
“HCM is an inherited disease resulting from mutations in heart muscle proteins,” notes Moore. “However, it is not known why the mutations lead to a pathological thickening of the heart chamber walls.”
The team hopes its research will lead to new diagnostic tools and screening for the early detection of these protein mutations and help develop new targeted drug therapies.
A Silent Killer
Heart muscle contracts and relaxes as a result of a regulatory switching phenomenon in response to changes in concentrations of calcium within the muscle cells.
“We are studying how the heart muscle’s on-off switching is regulated by calcium and how this is altered by disease-causing mutations,” explains Moore.
He says one of the challenges in treating people with HCM is that the treatments are often given at later stages of the disease, when secondary changes have already occurred in the heart.
“Our goal is to try to define what the underlying processes are at the critical initial stages of the disease,” says Moore. “We hope that the information revealed by our research will transform our fundamental understanding of heart muscle contractile function and dysfunction, leading to the design of new therapeutics.”
Moore’s research team includes graduate students Sailavanyaa Sundar, Stephen Hollenberg, Kayla Wilson and HyunJu Son and postdoctoral associate Alice Ward-Racca. Laboratory work is being conducted at Moore’s lab
in Olsen Hall on North Campus as well as at Yale and BU School of Medicine.
“Prof. Lehman’s group provides expertise in structural biology and computational chemistry. My lab provides ‘in vitro’ biophysical measurements of the heart muscle’s contractile protein function, while Prof. Campbell’s lab provides expertise in generating engineered heart tissue,” Moore adds.