Immunoflourescent microscopic image of human iPSC-derived cardiomyocyte stained with sarcomeric marker, alpha sarcomeric actinin, and counterstained with DAPI.


Genetic and acquired cardiomyopathies are significant causes of morbidity and mortality. Despite years of research, few disease-modifying therapies are available. To enable development of new therapies, we model cardiac diseases with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes. Ongoing projects are focused on modeling both heritable and acquired myocardial diseases, and include studies of a pathogenic variant of MYH7. By elucidating disease mechanisms in human cells, we hope to better translate our discoveries into therapies.

Goals and Approaches

We aim to better understand the molecular basis of genetic and acquired cardiomyopathies in order to develop novel therapies. Our approaches include:

  • Modeling of genetic and acquired cardiac diseases by using patient-specific hiPSC-derived cardiomyocytes
  • Use of gene-editing technologies to generate isogenic hiPSCs with clinically important pathogenic variants
  • Phenotyping of hiPSC-CMs with high-throughput functional assays

​Current Projects

High-throughput characterization of variants of unknown significance

Variants of unknown significance (VUS) present a challenge for clinical geneticists and patients. Discovery of a VUS in a patient with myocardial disease can have an emotional impact on patients and family members and often leads to further testing of significant cost and uncertain value. Pathogenic variants in the myosin heavy chain 7 gene (MYH7) are among the most common causes of genetic cardiomyopathies; however, numerous MYH7 variants are classified as VUS. We combine gene-editing techniques with high-throughput functional assays, with an ultimate goal of classifying all MYH7 VUS as pathogenic or not. Patients with pathogenic variants will merit further surveillance and treatment whereas patients with benign variants can be reassured.

Mechanistic studies in human iPSC-derived cardiomyocytes

Because sarcomeric mutations can lead to the accumulation of toxic myocardial proteins known as “poison peptides,” we are interested in defining cellular pathways that regulate clearance of sarcomeric proteins. Our long-term goal is to apply this knowledge to develop drug therapy that would accelerate poison-peptide clearance, improve cardiomyocyte function, and prevent disease caused by pathogenic sarcomeric variants. We developed new confocal microscopy techniques and are applying these techniques to measure sarcomeric protein dynamics.  We also determine whether cardiomyocyte function is impacted by experimental manipulations that alter protein clearance pathways.