Jason Fish

Research Synopsis

Endothelial cells integrate changes in the microenvironment to elicit an appropriate biological response, and therefore play key roles in health and disease.

The Fish lab investigates the molecular mechanisms that control endothelial cell biology. For example, we are seeking to decipher the signaling pathways and downstream transcriptional mediators that control responses to differentiation signals (e.g. artery/vein specification and angiogenesis) as well as pro-inflammatory factors.

We have identified important roles for noncoding RNAs such as microRNAs in modulating signaling pathways in endothelial cells. For example, we identified a microRNA, miR-146a, which is induced by inflammatory signaling pathways and acts as a negative feedback regulator to quench endothelial cell activation.

We have recently discovered that endothelial cells can package anti-inflammatory microRNAs into secreted extracellular vesicles and that these vesicles can suppress monocyte activation through microRNA transfer.

Studies from our lab and others are revealing an elaborate cell-cell communication network among cells in the cardiovascular system that is mediated in part by microRNA transfer. This is an exciting area of cardiovascular biology that is likely important for homeostasis and disease. Our current work is seeking to determine the role of long non-coding RNAs and microRNAs (particularly circulating microRNAs) in cardiovascular disease pathology.

We utilize a multi-disciplinary approach for our studies of endothelial cells, which includes zebrafish developmental biology models, mouse models of vascular disease, cultured human endothelial cells and assessment of human clinical samples.

Our experimental approaches include the analysis and functional interrogation of cell signaling and gene expression pathways, genome-wide approaches to uncover transcriptional networks, genome engineering using CRISPR technology, and investigation of extracellular vesicle biology.