Karen Maass, PhD

Our laboratory is broadly interested in cardiac development and stem cell biology. To study cardiomyocytes in health and disease, we generate stem cell models or transgenic mice by introducing reporter genes or mutations into the DNA of pluripotent stem cells. Using these models, we optimize the properties of cardiomyocytes derived from pluripotent stem cells for their useful application in pharmacological, personalized medicine, and regenerative medicine approaches.

Leveraging the insights from stem cell models, transgenic models, and biobank samples, our lab is interested in three major research interests:

What factors determine human cardiac conduction system differentiation and can we leverage these mechanisms to generate these cells from human-induced pluripotent stem cells (hiPS)?

How are noncoding RNAs involved in the development, homeostasis, and pathophysiological remodeling of the cardiac conduction system?

Can we study and better understand the mechanisms underlying increased cardiovascular comorbidity of people with HIV infection who are undergoing antiretroviral therapy using hiPS-derived cardiomyocytes?

One focus of our research is the directed differentiation of cardiomyocyte subtypes. The cells of the specialized cardiac conduction system represent only about one percent of all heart muscle cells. Due to the paucity of this cell type, its pathology and the precise arrhythmogenic mechanisms are poorly understood. Ventricular arrhythmia, especially, can be life threatening and the efficacy of antiarrhythmic drug treatments has been very disappointing.

Employing mouse stem cell models, we have identified candidate modifier genes, including noncoding RNAs, specifically enriched in cells of the ventricular conduction system (Purkinje cells). We postulate that forced expression of these or related human factors during cardiomyocyte differentiation from pluripotent stem cells will increase the yield of in vitro-generated Purkinje cells. We propose that these cells will then serve as a platform for target discovery, improving the development of novel treatments for patients at risk of life-threatening cardiac arrhythmias.

We recently also turned our attention to the effects of HIV and antiretroviral therapy on cardiomyocyte function. People with HIV infection are living longer due to successful antiretroviral therapy, but they are showing accelerated appearance of age-related diseases, including heart disease and stroke. However, the mechanisms by which HIV compromise cardiovascular function are poorly understood. Complementing the research of our collaborators, who are investigating transcriptomics, lipidomics, and metabolomics in human samples (NNTC, Manhattan brain bank, and CHARTER), we are focusing on the effects of HIV-TAT on hiPS-derived cardiomyocyte transcriptomics and function.

Together, we will integrate the differential “omics” profiles to gain insight into biochemical or signaling pathways modified by HIV infection and antiretroviral therapy, with special regard to pro-fibrotic and pro-inflammatory pathways. This insight will direct the analysis of candidate serum or exosome biomarkers to predict the cardiovascular risk of people with HIV infection.