Dr. Jason Fish completed his PhD at the University of Toronto in the laboratory of Dr. Philip Marsden in 2006, followed by postdoctoral training in the laboratory of Dr. Deepak Srivastava at the Gladstone Institute of Cardiovascular Disease and the University of California, San Francisco.
Dr. Fish has been a Scientist at the Toronto General Research Institute and an Assistant Professor at the University of Toronto since 2010. He was promoted to Senior Scientist and Associate Professor in 2016. Dr. Fish holds the Canada Research Chair in Vascular Cell and Molecular Biology.
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.
Rathnakumar K and Fish JE. Boosting endothelial autophagy by microRNA delivery quenches vascular inflammation. Circulation Research. 2018 Feb 2;122(3):388-390.
Nguyen MA, Karunakaran D, Geoffrion M, Tandoc K, Cheng HS, Perisic L, Hedin U, Maegdefessel L, Fish JE, Rayner KJ. Extracellular vesicles secreted by atherogenic macrophages transfer microRNA to inhibit cell migration. Arteriosclerosis, Thrombosis and Vascular Biology. 2018 Jan 38(1):49-63.
*Nikolaev SI, Vetiska S, Bonilla X, Boudreau E, Jauhiainen S, Jahromi BR, Khyzha N, DiStefano P, Suutarinen MB, Kiehl TM, Pereira VM, Antonarakis SE, Krings T, Andrade-Barazarte H, Tung T, Valiante T, Zadeh G, Tymianski M, Antonarakis SE, Wythe JD, Rauramaa T, Yla-Herttuala S, *Frosen J, *Fish JE, *Radovanovic I, Somatic activating KRAS mutations in arteriovenous malformations of the brain. New England Journal of Medicine. 2018 Jan 18;378(3):250-261. *Corresponding authors, equal contribution.
Gustafson D, Veitch S and Fish JE. Extracellular vesicles as protagonists of diabetic cardiovascular pathology. Frontiers in Cardiovascular Medicine. 2017 Nov 9;4:71.
Cheng HS, Besla R, Li A, Chen Z, Shikatani EA, Nazari-Jahantigh M, Hammoutene A, Nguyen MA, Geoffrion M, Cai L, Khyzha N, Li T, MacParland SA, Husain M, Cybulsky MI, Boulanger C, Temel RE, Schober A, Rayner KJ, Robbins CS, Fish JE. Paradoxical suppression of atherosclerosis in the absence of microRNA-146a. Circulation Research. 2017 Aug 4;121(4):354-367.
*Fish JE, *Gutierrez MC, *Dang LT, Khyzha N, Chen Z, Veitch S, Cheng HS, Khor M, Antounians L, Njock MS, Boudreau E, Herman AM, Rhyner AM, Ruiz OE, Eisenhoffer GT, Medina-Rivera A, Wilson MD and +Wythe JD, Dynamic regulation of VEGF-inducible genes by an ERK-ERG-p300 transcriptional network. Development. 2017 July;144(13):2428-2444. *Authors contributed equally.
Khyzha N, Alizada A, *Wilson MD, *Fish JE. Epigenetics of atherosclerosis: emerging mechanisms and methods. Trends in Molecular Medicine. 2017 Apr;23(4):332-347. *Corresponding authors.
Njock MS, Fish JE, Endothelial miRNAs as cellular messengers in cardiometabolic diseases. Trends in Endocrinology and Metabolism. 2017 Mar;28(3):237-246.
Cheng HS, Fish JE. Neovascularization driven by microRNA delivery to the endothelium. Arteriosclerosis Thrombosis and Vascular Biology. 2015 Nov;35(11):2263-5.
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.
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):949-966.
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.