1. Ongoing Research Projects 

1. Advancing knowledge of EV formation/signaling in diabetes and hypertension.
We initially identified molecular mechanisms governing endothelial EV formation in hypertension and established that endothelial EVs directly promote vascular injury. Building on this, we established that the bioactivity of EVs is altered by diabetic conditions leading to further vascular injury (Diabetologia 2017, IJMS 2023). We have further showed that high levels of endothelial EVs predict adverse outcomes in pregnant women with type 1 diabetes (Biomarker Res 2021). More recently, we have observed increases shedding of mitochondrial DNA into EVs in gestational diabetes as well as associations between endothelial EVs and cardiac dysfunction (IJMS 2022). Our CIHR-funded project is currently utilizing EVs and molecular approaches to characterize the maternal endothelium in gestational diabetes mellitus.

2. Large extracellular vesicles as markers/mediators of kidney disease.
My laboratory has been at the forefront of establishing new tools for measuring urinary EVs and assessing their signaling. We were the first to use flow cytometry to quantify urinary vesicles and establish that podocyte EVs are markers of kidney injury in diabetes (JASN 2014, Diabetologica 2017, 2020). Recent work shows that this approach can be applied in nephrotic syndrome (NDT 2023). Our lab is also involved in international efforts to advance the study of EVs in kidney disease.

3. Alterations in EV formation in aging
Our group was amongst the first to show that EV formation is altered in the process of cellular aging (JAHA 2012), notably exhibiting a shift towards large (ectosome) EV release away from smaller (exosome) EV formation. Building on this observation and our labs extensive efforts showing beneficial effects of small EVs and deleterious vascular effects of large EVs our NSERC Discovery Grant funded program aims to identify mechanisms driving aging-associated shifts in EV formation.

4. Role of neutrophil extracellular traps in vascular disease
An emerging theme in my research lab is the study of neutrophil extracellular traps (NETs), extracellular strings of DNA released by neutrophils. We are developed a high throughput assay for evaluating NET formation using AI-guided image analysis and studying the role of NETs in chronic kidney pathogenesis in a project funded by the Kidney Foundation of Canada.

5. Extracellular vesicles in renal replacement
In collaboration with Dr. Marcel Ruzicka we have evaluated the impact of renal replacement on extracellular vesicles. First, we showed that EVs are increased during peritoneal dialysis and may be used to assess peritoneal membrane injury (Can J Kid Health Dis 2017). We have shown that EVs are removed from circulation during a hemodialysis session through adsorbance to dialysis membranes (BMC Nephrology 2019). More recently, our Kidney Foundation of Canada-funded project examines sex differences in the release of EVs on dialysis and their ability to predict outcomes.


2. Other Research Interests

a. Therapeutic potential of vascular progenitor-derived EVs
b. Novel techniques for submicron particle assessment