Research

Pressure overload causes pathological cardiac hypertrophy and fibrosis and ultimately leads to fibrotic damage and heart failure. Along with structural changes in cardiomyocytes, the inflammatory cascade is activated in the heart as a response, which drives fibrotic changes in the LV with an infiltration of proinflammatory and matrix-producing cells. Neutrophils are the early responders in tissue injury. While their role in other cardiac injury is well defined, the role of neutrophils during pressure overload is unknown. This project aims to study the role of neutrophils in mice model of pressure overload after transaortic constriction (TAC). Using antibody-based neutrophil depletion technique, we aim to identify how neutrophils coordinate in the overall process of cardiac remodeling after TAC. 

Much background is known about how adult cardiac myocytes are different from fetal or neonatal ones, but little is known about the precise timings of when changes between them occur. For example, the switch from glycolysis to oxidative phosphorylation in cardiomyocytes, sarcomere distance and cell size increases, differences in cell populations, along with mitochondrial structure and organization are all known to change at some point between late embryonic development and adulthood. Here, we report more precisely when these hallmarks of maturation begin to change most to provide a timeline of the order of events that are necessary for structural and physiological maturation. We show that certain changes are continuous in growth from birth all the way into adulthood while others seem to reach their maximal development at distinct periods. The goal of this timeline is ultimately to be able to mimic normal cardiac development in vitro to create physiologically adult cardiomyocytes out of currently fetal-like cardiomyocytes derived from human induced pluripotent stem cells using different biochemical cues at the appropriate times.

Duchenne Muscular Dystrophy (DMD) results in progressive and incurable cardiomyopathy, leading to significant morbidity and mortality due to heart failure. There is currently no effective cure for DMD that can correct the genetic defects and compensate for the lack of dystrophin. Therefore, the therapeutic strategies that focus on the transplantation of induced pluripotent stem cells (iPSCs) derived cardiomyocytes are promising options, and remain to be investigated to what extent they can restrain the cardiomyocyte loss phenotype and improve cardiac function.