Poster #035
Investigating Cardiac Pathologies in Friedreich’s Ataxia using iPSCs
Mentor: Sebastian Ochoa-Vazquez, Student (Medical Center)
Friedreich’s Ataxia (FRDA) is a genetic disorder that causes progressive nervous damage which affects movement and cardiac complications, such as cardiac hypertrophy and dysfunction. Mutations within the Frataxin (FXN) gene causes reduced production of frataxin, a protein essential for mitochondrial function. We hypothesize that frataxin deficiency may disrupt lysosomal function to induce mitophagy, which in turn causes a buildup of dysfunctional mitochondria and subsequent contractile dysfunction. We will use human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and compare iPSC-CMs with and without FXN gene knockdown to reduce FXN expression. To confirm the gene knockdown, we will perform qPCR and western blotting. We will then evaluate mitochondrial function and biogenesis using Seahorse assays. Lastly, to examine lysosomal function and mitochondrial quality control, we will analyze TFEB and LC3A/B levels in the cells. The goal of this project is to better understand cardiac pathologies associated with frataxin deficiency in Friedreich’s Ataxia.