Marie-Sklodowska-Curie Fellowship for Ben Johnson

Ben Johnson, postdoc in the lab of reNEW Leiden AI Richard Davis and PI Christine Mummery, has been awarded a Marie-Sklodowska-Curie fellowship. He will use the fellowship to develop a clinically relevant model for myocardial infarction (MI) based on human induced pluripotent stem cells (hiPSCs). The system will allow the identification of therapies that boost heart muscle cell division and thereby replace myocardial tissue after myocardial infarction.

Cardiovascular diseases are the leading cause of death in the Western world and MIs are a major contributor to this. MIs are caused by a blood clot in the coronary arteries. As a consequence, parts of the heart are deprived of oxygen and nutrients which leads to necrosis of millions of heart muscle cells that are permanently lost and replaced by scar tissue. Despite the clinical need for new treatments that can restore the number of heart muscle cells, studying MIs has been challenging due to a lack of accurate human model systems.

With the Marie Curie fellowship, Johnson will aim to develop such a human model system that could contribute to the identification of novel therapies for MI in the future. The Marie Curie adds to ongoing work for which Johnson recently received an NWO-XS grant. He says: “I feel honored to have been awarded this prestigious fellowship. The Marie Curie is a real boost to my work in the lab of Richard Davis and will allow me to develop a hiPSC based disease model for studying MIs.”

Combining expertise
In order to develop the hiPSC based MI model, Johnson will make use of the specific expertise of reNEW PI Christine Mummery and AIs Richard Davis and Valeria Orlova. He explains: “First, we will employ the STRAIGHT-IN system that was developed in the Davis lab to generate iPSC lines that contain an inducible kill-switch. This will allow us to induce necrosis in a population of heart muscle cells derived from these hiPSCs.”

Building on knowledge from the Orlova lab, he will then incorporate these genetically modified heart muscle cells into healthy cardiac microtissues containing immune cells. Induction of cell death in this small incorporated population of heart muscle cells during a pseudo MI will closely mimic the situation during a real cardiac infarction. Johnson: “The microtissues mimic the human heart’s in vivo composition and will contain not only heart muscle cells, but also cardiac fibroblasts, vasculature and macrophages. This means we can investigate the role of the immune response following the pseudo MI, and how we can improve the wound healing process.”

Finally, Johnson will make use of reporter hiPSC lines being developed by the Mummery lab that track the cell cycle state of heart muscle cells. “Boosting division of surviving heart muscle cells holds great promise to replace lost tissue and restore cardiac function after an MI. These reporter lines will allow us to identify compounds that promote this heart muscle cell division, thereby inducing cardiac regeneration” explains Johnson. The model could therefore lead in the future to the identification of novel therapies for patients that suffer a myocardial infarction.

Image: Cardiac microtissue containing heart muscle cells (green), vasculature (red) and macrophages (white). Cell nuclei are shown in blue. Credit: Ulgu Arslan.

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