SBME Presents – Dr. Michael Regnier

Engineering hiPSC-Myocytes to Treat Heart Failure & Study Disease

In-Person Location: Life Sciences Centre 1003/Lecture Theatre 3

Virtual:  Zoom Meeting ID: 692 2606 9155; Passcode: 667943

Abstract:

Human inducible pluripotent stem cells (hiPSCs) are also being developed as a cell replacement approach for treatment of myocardial infarct and other forms of DCM.  We have engineered hiPSCs to over-express the enzyme Ribonucleotide Reductase (RNR), which results in elevated 2 deoxy-ATP (dATP), a potent myosin activator that can improve cardiac function in multiple models of systolic heart failure.  Our recent work demonstrates that RNR over-expressing hiPSC-CMs can engraft into infarcted hearts and deliver dATP to the native myocardium, boosting left ventricular function.  Thus, these cells may act as small molecule production factories for delivery of a therapeutic agent ‘on-site to treat heart failure.  hiPSC-CMs have also emerged as a powerful tool to study muscle diseases, especially when combined with the power of gene editing technology using CRISPR-Cas9.  Cardiac myocytes derived from hiPSCs (hiPSC-CMs) can be used to study genetic forms of cardiomyopathy, offering a human model with a potentially unlimited source of cells.  We have studied mutations in several sarcomere proteins associated with hypertrophic and dilated cardiomyopathies (HCM, DCM) and demonstrated contractile and structural abnormalities that may represent initiation of cellular compensatory responses in the disease process.

Speaker

headshot of Dr. Michael Regnier

Dr. Michael Regnier

Professor  |  Institute for Stem Cell & Regenerative Medicine, University of Washington

Dr. Regnier’s laboratory studies the molecular mechanisms of cardiac and skeletal muscle disease and uses this information to develop novel gene therapies and proteins, cells and tissue engineering approaches for treatment of disease.

The goal of the HAMM lab’s research is to understand the molecular and cellular mechanisms that regulate muscle contraction and its dysfunction with disease. They use a variety of molecular biology, genetic, and biomechanical, and computational modeling approaches. The knowledge gained from these experiments is used to design gene therapies and cell/tissue replacement approach to improve the performance of diseased cardiac and skeletal muscle. Many research projects are done in collaboration with other laboratories at the University of Washington, at other institutions across the US, and in Europe.