Dr. Robert Myette
Award: KRESCENT New Investigator Award
Institution: Children's Hospital of Eastern Ontario Research Institute
Year: 2026-2029
Project Title: Urinary EVs in Nephrotic Syndrome: Biomarkers and Causal Drivers?
Topic(s): Glomerulonephritis
Biography
Dr. Robert Myette is a pediatric nephrologist-scientist at the Children’s Hospital of Eastern Ontario (CHEO) and the CHEO Research Institute, an Assistant Professor at the University of Ottawa, and the CHEO Foundation Research Chair in Pediatric Kidney Disease. His research program investigates the cellular mechanisms underlying childhood nephrotic syndrome, with a particular focus on podocyte injury, extracellular vesicle biology, and kidney cell-to-cell communication.
Lay Summary
Background: Nephrotic syndrome (NS) is one of the most common kidney diseases in children. NS is associated with significant protein loss in the urine, leading to swelling, increased risk of infection, blood clots, and early heart disease. This results in a significant burden for children, their families, and the health care system. The main cause of NS is unknown, yet treatment is standardized: children receive large doses of steroids. This often leads to unpleasant side effects, including weight gain and mood changes. It is unclear who will need only one course of treatment and who will require many. We must diagnose and treat NS better and decrease steroid exposure to minimize these side effects.
Purpose: To do this, we aim to better understand the podocyte, or “foot cell,” a sieve-like kidney cell responsible for filtering blood and preventing protein loss. NS is a disease of the foot cell. When stressed, these cells release small particles called extracellular vesicles (EVs) into the urine, allowing us to study what is happening inside the foot cell without an invasive biopsy. Our group has shown that children with NS have higher levels of foot cell EVs in their urine. In this project, we will focus on how these EVs are formed and how specific proteins are selected and packaged, with attention to a protein called S100A10 that appears to help control this process. We will study EVs using foot cells in the lab and urine samples from children. Because we cannot know the full ‘grocery list’ of items packaged into EVs, we must study them closely in the lab to understand each component. This will clarify how the foot cell behaves in health and disease.
Methods: Our first aim is to understand the ‘grocery items’ within EVs from foot cells in the lab. Secondly, we aim to understand how EVs are filled and released from foot cells. Specifically, we will examine how S100A10 acts as a coordinator inside the cell, helping control EV formation and which proteins are selected for packaging. By carefully studying how EVs are built and loaded, we can determine whether this process is organized and purposeful rather than random.
Anticipated Outcomes: Building on our work showing that foot cell EVs are elevated in children with NS, we anticipate that EVs differ in their ‘grocery items,’ suggesting the foot cell selects different contents under different conditions. We expect that S100A10 helps organize this selection process, meaning that packaging is controlled rather than random. These selected items will help explain why they are packaged and how they reflect the health of the foot cell. Understanding this ‘grocery list’ may help determine which children will respond to steroids and who may require alternative treatments.
Patient Engagement: Through engagement with our Nephrology Clinic at CHEO and collaboration with the family research leadership program at the CHEO Research Institute, we will ensure our work remains patient-centered and relevant. We will communicate findings through lay summaries, infographics, and a “Nephrotic Syndrome Night” at CHEO to share results directly with families (See Support Letter).
Relevance to Patients and Communities: This work is directly relevant to children and families affected by NS. Treatment relies on high-dose steroids with significant side effects, and 10–20% of children are steroid resistant. By understanding how foot cell EVs are formed and how key proteins regulate this process, we hope to clarify disease mechanisms, and improve diagnostic and treatment strategies.
Conclusion: This research builds on our existing results to better understand foot cell EVs in NS (KFOC KHRG Grant), not only as non-invasive biomarkers of steroid responsiveness but also as indicators of how stress within the foot cell leads to controlled release of specific signals. By uncovering the molecular rules that govern EV formation and packaging, we move closer to understanding the root causes of this disease. This work could change how we treat children and youth with NS. As a clinician caring for these patients, I am committed to developing more effective and personalized treatment approaches.