PHA Proof of Concept Research Grant Winner 2014

Frances S. de Man, PhD

Frances S. de Man, PhD

Assistant Professor
Department of Pulmonology
VU University Medical Center, Amsterdam
Title: “A New Tool to Obtain Novel Insights in PAH-Induced Right Heart Failure”
Term: December 1, 2014- November 30, 2015

The Jerry Wojciechowski Pulmonary Hypertension Proof of Concept Grant

Summary of Research Project:

Current understanding of right heart failure development is hampered by limited availability of cardiac tissue of PAH-patients. In addition, cardiac tissue can only be obtained during heart-lung transplantation or autopsy, which is end-stage disease. Ideally, RV tissue should be obtained multiple times during the disease development. This is not possible because RV biopsies are not without significant risk and not clinically indicated. Recently, it was described that inducible pluripotent stem cells could be isolated from venous blood of patients with pulmonary arterial hypertension. An important characteristic of inducible pluripotent stem cells is their ability to transform to different cells, for instance cardiac cells. In this study, Dr. de Man and her team will isolate inducible pluripotent stem cells of PAH-patients, transform them to cardiac cells and make patient specific 3D-engineered heart tissue. Because these cells can be isolated from venous blood, we are able to follow right heart failure development over time. More importantly, by combining functional measurements with genetic or therapeutic interventions, we will be able to identify, for the first time, which mechanisms drive right heart failure development in human PAH.