Penn to Co-Lead $6.5 Million Transatlantic Grant to Investigate Role of Immune System in Heart Disease

Epstein
Jonathan Epstein, MD

PHILADELPHIA — An international research collaboration to pioneer the field of immuno-cardiology and investigate ways to harness the power of the immune system to improve recovery from heart attacks will be led at the Perelman School of Medicine at the University of Pennsylvania by Jonathan Epstein, MD, executive vice dean, chief scientific officer and the William Wikoff Smith Professor of Cardiovascular Research. The effort is supported by a newly awarded $6.5 million Leducq Foundation grant.

“Heart disease remains the number one killer in the western world, and there is a growing understanding of the role of the immune system in how you recover from it,” Epstein said. “With the Leducq Award, we can take advantage of the great strengths at Penn in knowing how to read the language of the immune system and how to harness the immune system to improve recovery. This is also a terrific opportunity for collaboration with researchers across institutions and across continents.”

The research team 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 Leducq Foundation funded only four transatlantic research consortiums in 2020, two of which are affiliated with Penn. Benjamin L. Prosser, PhD, an assistant professor of Physiology, will serve as the North American coordinator for a second Leducq award. This group will expand upon previous research investigating the enzymatic modifications driving change in the cytoskeleton and microtubule behavior in heart cells 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.

Penn is an internationally recognized center of groundbreaking discoveries in immunology and immunotherapy. With the largest single-institution immunology community in the nation, numbering more than 200 experts, Penn researchers and scientists have harnessed the immune system to develop groundbreaking approaches to fight HIV and other infectious diseases, cancer, autoimmune diseases, and heart disease. Their work has included the first FDA approvals for CAR T cell therapies for pediatric and adult blood cancers, and vaccine research that’s paving the road to functional cures for HIV.

“There is a growing understanding of the role of the immune system in many diseases, maybe all diseases,” Epstein said. “The idea that the immune system can play a critical role in how you recover from a heart attack, and other types of heart disease, though, is relatively new.”

While it is clear that inflammation contributes to heart disease, the role different cells in the immune system play in the heart is limited and little information exists regarding the precise immune cells that promote disease and the signaling mechanisms that exert their effects. Thus, it has remained challenging to effectively target inflammation and fibrosis in the human heart. Researchers plan to establish the molecular basis by which inflammation in the heart orchestrates key elements of fibrosis, accelerate innovation in immune-cardiology through team science, and train the next generation of scientists studying cardiovascular health.

This work will be supported by previous research led by Epstein and Haig Aghajanian, PhD, a postdoctoral researcher of Cell and Developmental Biology, which involved engineering T cells to target cardiac fibrosis, a scarring process common to most forms of heart disease. That study, published in Nature in 2019, used a modified T cell receptor called a CAR-T to target cardiac fibroblasts involved in cardiac fibrosis.

Aghajanian will join the research team funded by the Leducq Award. Other researchers from Penn include Hao Wu, PhD, an assistant professor of Genetics, Cheryl L. Smith, PhD, a senior research investigator of Cell and Developmental Biology, Joel G. Rurik, a doctoral student in Cell and Development Biology, and Peng Hu, PhD, a postdoctoral researcher of Genetics.

Previous Leducq awards at Penn went to Mark L. Kahn, MD, a professor of Cardiovascular Medicine, to study lymphatic vascular defects and their contribution to common human cardiovascular diseases, and Daniel J. Rader, MD, chair of Genetics, to study the molecular mechanisms of some of the most compelling genes to come out of genome-wide association studies (GWAS) for coronary heart disease and heart attack.

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