Penn to Co-Lead $6.5 Million Transatlantic Grant to Investigate Cytoskeleton’s Role in Heart Disease

PHILADELPHIA—Benjamin L. Prosser, PhD, an assistant professor of Physiology in the Perelman School of Medicine at the University of Pennsylvania, will serve as the North American coordinator for a new, multi-institutional $6.5 million grant from the Leducq Foundation, aimed at better understanding the role the heart cell cytoskeleton plays in heart disease and finding new ways to treat it.

The consortium is made up of physician-scientists and researchers across seven labs from Europe and North America and funded under the foundation’s 2020 Transatlantic Networks of Excellence Program. The teams will spend five years collaborating and working toward the shared goal of finding new therapies that target the cytoskeleton – the internal structure of heart cells that influence how well the heart can pump blood – to prevent or reverse cardiac disease and failure.

Researcher and transplant cardiologist Kenneth B. Margulies, MD, a professor of Medicine at Penn, is also a member of the consortium and is Prosser’s collaborator.

“Leducq seeks to bring together researchers from really disparate backgrounds and diverse areas of expertise in order to tackle a big problem in the cardiovascular space in new and innovative ways,” Prosser said. “The idea is to bridge these collaborations across the pond and accomplish a goal that any one, two, or even three investigators alone could not.”

Heart failure is caused by the loss of heart muscle and/or a change in the ability of heart muscle cells to properly contract. Inside each heart muscle cell is a network of microtubules and protein filaments that make up the cytoskeleton. While past investigations have looked at exploiting the motor proteins or regulation of calcium in heart muscle cells, targeting the cytoskeleton, specifically, is a relatively new and unexplored territory of cardiac research.

The Penn researchers have shown in past studies the enzymatic modifications driving change in the cytoskeleton and documented, using advanced imaging techniques, microtubule behavior in heart cells. This new award will expand upon that research to focus on the normal roles of the cytoskeleton, how it changes or becomes compromised during heart disease and failure, and ultimately new ways to target those changes to restore heart function.

Lucie Carrier, PhD, of the University Medical Center Hamburg in Germany, will serve as the European coordinator. The other institutions involved in this work include Johns Hopkins University School of Medicine, Brigham and Women’s Hospital, Technion Israel Institute of Technology, France’s Grenoble Institut des Neurosciences, and the Amsterdam Vrei University Medical Center.

The consortium, known as the Leducq Cytoskeleton Network, will also allow for the exchange of young investigators across the labs as part of an effort to provide stronger training experiences for the next generation of scientists, as well as share ideas and strengthen the collaborations among the groups.

The Leducq Foundation was created with the idea that the battle against cardiovascular and stroke should be waged at the international level, according to the foundation’s website. By forging scientific alliances that transcend national borders, and educating young researchers who thrive in an international context, it strives to promote innovation and develop long-term collaborative relationships. Since 1996, it has awarded more than $300 million in grants for worldwide research.

“Science is already a team sport. But this is going a step beyond and expanding to different labs and institutions and even continents,” Margulies said. “I think we found a really good team that complements one another and will allow us to cross pollinate each other’s work.”