The AHA and the Paul G. Allen Frontiers Group have awarded two $1.5 million grants to study the extracellular matrix.
The grants will help investigators uncover the next breakthrough in heart-health research by studying the role the ECM may play in everything from tissue repair to cell-to-cell communication.
The 2017 AHA-Allen Distinguished Investigators are Suneel Apte, MB, BS, a researcher at the Lerner Research Institute at the Cleveland Clinic in Ohio, and Jeffrey Holmes, MD, PhD, professor of biomedical engineering and founding director of the Center for Engineering in Medicine at the University of Virginia in Charlottesville.
“Given that cardiovascular disease remains an unsolved mystery and a tremendous burden to society, we were pleased to work with the world’s leading heart association to hopefully solve this difficult problem,” said Tom Skalak, PhD, executive director of the Paul G. Allen Frontiers Group in Seattle, Washington.
“The AHA shares our passion for exploring new territory in science. In funding these two AHA-Allen Distinguished Investigators, we believe that the information content of the extracellular matrix can be decoded and used to define new therapies and heart-health measures.”
Apte’s research is focused on a class of enzymes called proteases that work like molecule scissors to remodel the extracellular matrix.
“That kind of activity is not visible on the surface or in a snapshot,” Apte said. “We have to dig deep for it, but it is important because cutting ECM molecules affects their function in a significant way.”
Apte and his team will define the extensive ECM remodeling that occurs by cataloging as many cut molecules in the heart and blood vessels as possible. They will also delete a protease and track changes in the extracellular matrix.
“This is truly fundamental knowledge with considerable potential for treating human disease,” Apte said. “That’s why the commitment to studying the ECM by the AHA and the Allen Group is important. This is an unexplored frontier that needs to attract greater awareness, more scientists and increased funding. This grant allows us to embark on ambitious projects that might not have been readily supported by other initiatives or agencies.”
Holmes’ research was inspired by the realization that the extracellular matrix turns over much more slowly than the cells that inhabit it or their parts. For example, the half-life of the actin and myosin in a myocyte is about one week, but collagen and elastin can last an entire lifetime.
“We think the implication of this simple fact is that much of the information about long-term processes such as aging is stored in the extracellular matrix and read back by cells to help direct their behavior,” Holmes said. “Our goal is to image this turnover in both space and time, so we can watch cells deposit and modify the ECM, and then see how other cells access that information.”
Holmes is studying heart mechanics, growth and remodeling. He is particularly interested in the scar that forms after a heart attack.
“Our work has led us into modeling and measuring extracellular matrix turnover in the heart and made us appreciate how important the cardiac extracellular matrix is for nearly everything that happens in normal heart development as well as in disease,” he said.
“The most exciting thing about the AHA-Allen partnership is that they asked us to think big — to propose something truly novel even if it’s risky. An opportunity to take a big leap instead of a single step is not only valuable, it’s fun.”