Jason Fish, Ph.D.
Toronto General Research Institute, University Health Network
and the University of Toronto
(From left to right) is: Henry Cheng, Shawn Veitch, Emilie Boudreau, Jason Fish, Zhiqi Chen and Nadiya Khyzha.
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.
If you find these areas of vascular biology exciting, we are always looking for highly motivated graduate students and post-doctoral fellows to join the lab. Toronto is a fantastic city and an excellent environment for collaborative cardiovascular research.
To learn more about Dr. Fish and his work, visit the lab website at http://www.uhnres.utoronto.ca/researchers/profile.php?lookup=1832
- Njock MS, Cheng HS, Dang LT, Nazari-Jahantigh M, Lau AC, Boudreau E, Roufaiel M, Cybulsky MI, Schober A and Fish JE. Endothelial cells suppress monocyte activation through secretion of extracellular vesicles containing anti-inflammatory microRNAs. Blood. 2015 May;125(20):3202-12.
- Fish JE and Wythe JD. The molecular regulation of arteriovenous specification and maintenance. Developmental Dynamics. 2015 Mar;244(3):391-409.
- Cheng HS, Njock MS, Khyzha N, Dang LT and Fish JE. Noncoding RNAs regulate NF-kappaB signaling to modulate blood vessel inflammation. Frontiers in Genetics. 2014 Dec;10(5):422.
- Delgado-Olguin P, Dang LT, He D, Thomas S, Chi L, Sukovic T, Khyzha N, Dobenecher MW, Fish JE, Bruneau BG. Ezh2-mediated repression of a transcriptional pathway upstream of Mmp-9 maintains integrity of the developing vasculature. Development. 2014 Dec;141(23):4610-7.
- Cheng HS, Sivachandran N, Lau A, Boudreau E, Zhao J, Baltimore D, Delgado-Olguin P, Cybulsky MI and Fish JE. MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Molecular Medicine. 2013 Jul;5(7):949-66.
- Wythe JD, Dang LT, Devine WP, Boudreau E, Artap ST, Schachterle W, Stainier DY, Oettgen P, Black BL, Bruneau BG and Fish JE. ETS factors regulate Vegf-dependent arterial specification. Developmental Cell. 2013 Jul;26(1):45-58.
- Dang, LT, Lawson, ND and Fish, JE. MicroRNA control of Vegf signalling output during vascular development. Arteriosclerosis, Thrombosis and Vascular Biology. 2013 Feb;33(2):193-200.
Henry Cheng, PhD student
Nadiya Khyzha, PhD student
Shawn Veitch, PhD student
Emilie Boudreau, Research technician
Zhiqi Chen, Research technician
Lan Dang (Post-doctoral fellow), currently a Post-doctoral fellow at Biogen in Boston
Sebastien Njock (Post-doctoral fellow), currently a Principal Investigator at the Catholic University of Cameroon