Dr. Jason Fish completed his PhD at the University of Toronto under the supervision of Dr. Philip Marsden. Here he uncovered a role for epigenetics in gene regulation in blood vessels. This was followed by a postdoctoral fellowship at the Gladstone Institute of Cardiovascular Disease and the University of California San Francisco under the supervision of Dr. Deepak Srivastava. Here, Dr. Fish uncovered a role for microRNAs in regulating the development of the cardiovascular system. Dr. Fish returned to Toronto in 2010. He was the Canada Research Chair in Vascular Cell and Molecular Biology (2013-2023) and the past-president of the North American Vascular Biology Organization.

Research Synopsis:

Endothelial cells are dynamic integrators of their microenvironment, translating physiological and pathological cues into coordinated biological responses. As key regulators of vascular function, they play central roles in both health and disease.

The Fish Lab investigates the molecular mechanisms that govern endothelial cell biology across a spectrum of vascular and cardiometabolic diseases. We discovered that somatic KRAS mutations within the endothelium are the primary cause of sporadic brain arteriovenous malformations (bAVMs). Building on this finding, we developed preclinical models of bAVM and leverage human patient-derived samples, including organoid systems and high-throughput screening platforms, to identify and test novel therapeutic strategies.

Our research also examines how systemic inflammation and endothelial activation may create a susceptibility to cardiac damage during chemotherapy. We study how tumours influence the cardiac vasculature, how endothelial cells respond to chemotherapeutic agents, and how they communicate with cardiomyocytes through extracellular vesicles. In other projects in the lab, we investigate how diabetes alters cardiac microvascular function and how heart failure affects the brain, with the goal of defining vascular mechanisms that link multi-organ disease.

We employ a multidisciplinary and translational approach that integrates zebrafish and mouse models of cardiovascular disease, cultured human endothelial cells, organoid systems, and analysis of human clinical specimens. The Fish lab is a vibrant training environment where intellectual curiosity, scientific rigor, and team science are valued. Close collaboration with clinician-scientists enables us to move discoveries from bench to bedside.

Our experimental toolkit includes functional interrogation of signaling and gene regulatory pathways, genome-wide approaches to define transcriptional networks, CRISPR-based genome engineering, high-throughput screening, and mechanistic studies of extracellular vesicle-mediated communication.