Cellular and Molecular Arrhythmia Research Program

The University of Wisconsin Cellular and Molecular Arrhythmia Research Program (CMARP) is a multi-investigator research group that focuses on the role of cardiac ion channels in cardiac physiology, pharmacology and disease.

Founded in 1996 and one of the only groups of its kind in the nation, the CMARP team collaborates through weekly conferences, shared facilities and equipment, and participation in collaborative research projects.

Our work seeks to provide new understanding and therapies for inherited and acquired forms of arrhythmia and heart failure syndromes.

We invite cardiovascular medicine clinicians and researchers from other institutions to visit our labs and partner with us.

Congenital and Acquired Long Q-T Syndrome

Our investigators have been recognized worldwide for their discovery of molecular pathways by which mutations in the potassium channel gene, HERG, can lead to Long Q-T syndrome (LQT2), a disease manifested by potentially fatal ventricular arrhythmias often striking children and young adults.

Specifically, they found that defects in membrane trafficking of the mutant channels underlie the defect in repolarization of the cardiac action potential in many of the disease-producing mutations of HERG.

Micropatterning Ventricular Cardiac Tissue Units

More recently, the team has used technology developed at UW-Madison to induce human pluripotent stem cells from human skin and blood samples. They they "reprogram" these stem cells into becoming ventricular cardiomyocytes, fibroblasts and endothelial cells, which  work together to beat rhythmically and function as a kind of human heart-in-a-dish.

The team is now investigating ways to further micropattern these stem cell-derived heart cells into functional ventricular cardiac tissue units (vCTUs) that manifest properties of mature ventricular muscle and exhibit patient-specific arrhythmic behavior in response to provocation.

They are also developing an optical imaging platform to rapidly assess these vCTUs for patient-specific manifestations of arrhythmias and response to therapies.

Together, these efforts may open up completely new avenues for precision medicine-based diagnosis and treatment of lethal forms of arrhythmias.