Jennifer Lake, Ph.D.
Supervisor(s): Dr. Alexandra Cambier and Dr. Isabelle Sirois
Award: KRESCENT Post-Doctoral Fellowship
Institution: Centre Hospitalier Universitaire Sainte-Justine
Year: 2026-2028
Project Title: Unraveling Complement Activation in Focal Segmental Glomerulosclerosis
Topic(s): Glomerulonephritis
Biography
Jennifer Lake, PhD, is a postdoctoral research fellow at CHU Sainte-Justine and the Université de Montréal under the supervision of Dr. Alexandra Cambier and co-supervision of Dr. Isabelle Sirois. She earned her PhD from the University of Zurich, where she investigated molecular mechanisms driving inherited kidney diseases, with a particular focus on the role of uromodulin aggregation in autosomal dominant tubulointerstitial kidney disease. She subsequently completed a postdoctoral fellowship at the Institut Necker Enfants Malades in Paris, where she applied urinary proteomics to identify non-invasive biomarkers and therapeutic targets in autosomal dominant polycystic kidney disease. Her research integrates proteomics, extracellular vesicle biology, and translational nephrology to uncover molecular pathways driving kidney disease and transform them into clinically actionable biomarkers. Her current work focuses on defining pathway-specific complement activation signatures in pediatric nephrotic syndrome using advanced proteomic analyses of plasma, urine, and urinary extracellular vesicles. By identifying mechanistically informed biomarker panels capable of distinguishing focal segmental glomerulosclerosis from minimal change disease, predicting disease progression, and revealing targetable complement pathways, her research aims to advance precision medicine for children with glomerular diseases.
Lay Summary
Background: Idiopathic Nephrotic Syndrome (INS) is the most common kidney disease in children. It causes the kidneys to leak large amounts of protein into the urine. This leads to swelling, infections, blood clots, and, in severe cases, kidney failure. INS has two main forms: Minimal Change Disease (MCD), which usually responds well to steroid treatment and Focal Segmental Glomerulosclerosis (FSGS), which is often resistant to steroids and lead to higher risk of permanent kidney damage. Early diagnosis of FSGS is challenging, as it depends on invasive kidney biopsy. As a result, children may face delayed diagnosis and prolonged exposure to ineffective treatments with significant side effects. There is an urgent need for non-invasive tests that can help diagnose FSGS earlier and guide treatment decisions. Recent research suggests that part of the immune system, called the complement system, may play an important role in kidney damage in FSGS. The complement system is a group of proteins in the blood that normally helps fight infections. However, when it becomes overactive, it can damage kidney cells. We believe that measuring complement activity in blood and urine may help us better understand, diagnose, and eventually treat children with FSGS.
Purpose: We aim to identify a complement activation signature in children with FSGS. Rather than relying on a single marker, we will develop a multiplex panel, a combination of complement-related proteins and fragments, to: (i) distinguish FSGS from MCD without biopsy, (ii) predict disease severity and progression, and (iii) identify complement mechanisms for therapeutic intervention.
Methods: We will study blood and urine samples from children and adults diagnosed with INS. We will use advanced mass spectrometry approaches, which are innovative protein analysis techniques, to measure complement proteins and their breakdown products. These methods allow us to detect small protein fragments that reflect disease processes. First, we will perform broad protein profiling to give us a global view of what is happening. Second, we will use specialized techniques to identify specific complement fragments. These fragments act like footprints left behind when the complement system is activated. We will also separate particles in the urine called extracellular vesicles that are released by cells. They carry proteins from the kidney and may contain important clues about how complement is damaging kidney tissue. After identifying promising biomarkers, we will confirm our findings using enzyme immunoassays, which are additional tests that can also be used in clinical settings. Finally, we will compare our complement signature with clinical information such as biopsy results, response to treatment, kidney function, and disease progression.
Anticipated Outcomes: We expect to find that children with FSGS have a distinct complement activation pattern compared to those with MCD. We anticipate that combination of biomarkers will provide better diagnostic accuracy. This multiplex panel may improve our ability to: Identify FSGS earlier, predict disease severity and monitor disease over time. Our findings may also highlight specific parts of the complement system that could be targeted by future therapies.
Patient Engagement: Our project prioritizes collaboration with patient and parent partners from the beginning. Their involvement in study design and biomarker evaluation, will guarantee clinically relevant biomarkers and well-tolerated treatments, ultimately improving quality of life. The ongoing engagement of patient partners through research meetings and family-oriented events will support clear communication of results and help align future diagnostic tools with patients needs.
Relevance to Patients and the Community: Children with FSGS often face uncertainty, invasive biopsies, and prolonged exposure to medications that may not work. Our research aims to reduce that uncertainty for these children and their family. By developing a non-invasive test, we hope to improve early diagnosis and guide treatment decisions. Earlier diagnosis will help prevent kidney damage, optimize treatment, and minimize unnecessary steroid exposure, particularly benefiting children in remote areas with limited access to specialized nephrology care. In the long term, identifying specific complement pathways involved in FSGS may open the door to targeted treatments.
Conclusion: FSGS is a serious childhood kidney disease that is hard to diagnose early and treat effectively. Our goal is to develop a non-invasive complement-based diagnostic panel that improves classification, predicts progression, and lays the groundwork for precision therapies, ultimately improving the lives of children with FSGS.