The Gregorio Lab in the University of Arizona Sarver Heart Center’s Molecular and Cardiovascular Research Program (MCRP) was awarded $1.77 million from the National Institutes of Health (NIH) for a study called “Deciphering the Role of Lmod2 in Thin Filament Length Regulation and Dilated Cardiomyopathy” (NIH Grant 1R01HL123078).
“This award demonstrates the value of Sarver Heart Center’s Investigator Awards Program, which provides seed funding for promising research ideas,” said Carol C. Gregorio, PhD, head of the UA College of Medicine – Tucson Department of Cellular and Molecular Medicine, director of the MCRP and co-director of the UA Sarver Heart Center. She is the principal investigator on the NIH grant.
Under Gregorio’s mentorship, Christopher Pappas, PhD, a postdoctoral research associate, obtained a Sarver Heart Center Investigator Award funded by the Steven M. Gootter Foundation. With the funding, Pappas studied the role of the protein Lmod2 in cardiac development and dilated cardiomyopathy (DCM). The Investigator Award enabled Pappas to jump-start his path to career independence by obtaining the data necessary to compete successfully for the NIH grant as a co-investigator, said Gregorio.
Dilated cardiomyopathy causes the heart to become weakened and enlarged, frequently leading to heart failure and sudden cardiac arrest. It affects about 1 million people, making it the second most common cause of heart failure, behind heart failure due to heart attacks. More than 6 million people in the United States have heart failure.
“Cardiac muscle is composed of thick and thin protein filaments. In studying the heart’s mechanism of contraction, we found that the filaments have to be precisely organized for efficient beating. Proper contraction requires filaments of the proper length. We found that Lmod2 is an actin filament elongation protein that regulates the lengths of thin filaments in heart muscle,” said Pappas.
UA researchers have identified the connection between thin-filament length and cardiac function, as well as the role thin-filament length dysregulation plays in cardiomyopathies. Their goal is to uncover insights into novel therapeutic targets for dilated cardiomyopathy.
“We know that without Lmod2, hearts become enlarged and do not pump well. We can observe at very high magnification that heart muscle lacking Lmod2 is extremely disrupted. These data indicate that the absence of Lmod2 leads to dilated cardiomyopathy in animal models,” said Pappas.
Future directions for the research team include determining how short thin-filament lengths lead to dilated cardiomyopathy and if Lmod2 mutations are present in human patients with dilated cardiomyopathy.
The University of Arizona Sarver Heart Center Investigator Award Review Committee is meeting this week to select the next round of research award recipients. The Center’s 135 members, including faculty from cardiology, cardiothoracic surgery, pediatric cardiology, neurology, vascular surgery, radiology, endocrinology, emergency medicine, nursing, pharmacy and basic sciences, are eligible to apply for investigator awards each year. The UA Sarver Heart Center emphasizes a highly collaborative research environment, fostering innovative translational or “bench-to-bedside” research and working toward a future free of heart disease and stroke.
