Targeted Inhibition of Fibroblast Activation



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Cardiovascular disease continues to be one of the leading causes of death in the modern world. Due to the limited regeneration capacity of the mammalian heart, very few options exist to help restore cardiac function post infarct. One promising new avenue for treatment lies in the field of direct reprogramming—changing one cell type to another through a variety of viral cocktails and small molecules.The direct reprogramming field has made significant process in overcoming roadblocks; however, the efficiency of producing mature cardiomyocytes in vitro remains around 1%. Researchers hypothesize that when the cells are plated onto plastic or glass, many cells activate alternative signaling pathways, preventing them from becoming cardiomyocytes. If we could prevent such a large population of cells from converting to myofibroblasts, the efficiencies of in vitro direct reprogramming would skyrocket. Thus, my project looked into various methods that would help prevent myofibroblast formation, resulting in better reprogramming efficiency in the long run. This project was completed with contributions from Nikhil Munshi from the UT Southwestern Department of Internal Medicine Cardiology.