Date on Master's Thesis/Doctoral Dissertation
8-2023
Document Type
Master's Thesis
Degree Name
M.S.
Department
Pharmacology and Toxicology
Degree Program
Pharmacology and Toxicology, MS
Committee Chair
Mohamed, Tamer M.
Committee Member
Siskind, Leah J.
Committee Member
Jones, Steven P.
Committee Member
Clark, Geoffrey J.
Author's Keywords
Cardiac regeneration; cardiomyocyte; heart failure; myocardial infarctionEpigenetic
Abstract
The limited regenerative capacity of adult cardiomyocytes (CMs) is manifested in prevalent morbidity and mortality associated with ischemic heart disease. We previously demonstrated that a combination of four cell cycle factors (4F) promotes efficient cell division in differentiated CMs. The temporal transcriptional reprogramming in the 4F-transduced CMs indicates that epigenetic modifications mediate the cell cycle progression. Through small molecule screening, we evaluated the epigenetic impact on CM’s response in the 4F-transduced CMs. We identified the histone demethylase 5B (KDM5B), which through in vitro and ex vivo genetic knockdown and overexpression studies, exhibited a modulative effect on CM’s cell cycle plasticity along with transcriptional alteration in the cell cycle-related genes. Whereas KDM5B depletion impaired CM’s replicative capacity, its overexpression induced and augmented CM’s proliferation in a context-dependent manner. Our data indicate that KDM5B is essential for CM’s regeneration and cell cycle activation and is a potential target for myocardial repair.
Recommended Citation
Hammouri, Dana, "KDM5B as a potential epigenetic regulator of cardiomyocyte regeneration and cell cycle activation." (2023). Electronic Theses and Dissertations. Paper 4148.
https://doi.org/10.18297/etd/4148
