Embedded Files
Complement signaling in cardiac injury and renewal
Complement signaling in cardiac injury and renewal
The complement pathway is an innate immune pathway activated after injury in the heart. We found that specific niches of cardiomyocytes, fibroblasts, and macrophages increased expression of different complement pathway genes, and these cells/genes are crucial for cardiomyocyte proliferation. Additionally, the niche composition and complement genes activated in regenerative versus non-regenerative hearts are different. Our lab aims to determine the precise function of the complement pathway in each cell type in the heart, and to enhance adult heart post-injury remodeling by modulating this niche.
Cardiac renewal models - YAP5SA overexpression in adult cardiomyocytes and Neonatal myocardial infarction. Both models induce a pro-renewal niche with complement pathway activation.
Inhibtion of SUMO results in increased nuclear YAP (FLAG, yellow) in cardiomyocytes.
SUMOylation in cardiac renewal
SUMOylation is a post-translational modification where SUMO protein is covalently attached to another protein, modifying it's confomation, localization or function. The precise role of SUMOylation is largely unknown in adult ischemic injury and cardiac regeneration. We have found that many proteins required for cardiomyocyte proliferation are SUMOylated during cardiac renewal. For example YAP, a transcriptional coactivtor that can induce cardiomyocyte proliferation, is excluded from the nucleus when it becomes SUMOylated; inhibition of SUMOylation results in its nuclear retention and increased expression of YAP target genes. We aim to characterize the function of other SUMOylated proteins in cardiac renewal and identify their SUMOylation sites, with hopes to identify new therapeutic targets for adult cardiac injury.
Characterizion of pro-renewal immune cells
Immune cells are crucial for tissue repair and remodeling after injury. While many studies have examined their role in non-regenerative settings, very little is known about their composition, cell state, temporal dynamics and function in regenerative models. We are utilizing transcriptomic approaches combined with proteomic approaches to address these questions. Our goal is to reprogram adult immune cells to pro-regenerative neonatal immune cells.
A. Pro-renewal macrophages can directly affect cardiomyocytes or modulate the extracellular matrix. B. Mouse model for labeling newly synthesized peptides in macrophages. C. Labeling of newly synthesized peptides in cardiac macrophages.
Page updated
Report abuse