Current lab members:

• Barbara Seitz-Polski, Professor in Immunology, PU-PH, MD PhD, UniCa
• Marina Shkreli, CR, INSERM
• Marion Cremoni, University Hospital Assistant, PhD student, UniCa
• Maxime Teisseyre, University Hospital Assistant, PhD student, UniCa
• Céline Fernandez, MsC, engineer, CHU de Nice
• Kévin Zorzi, MsC, engineer, CHU de Nice
• Vesna Brglez, PhD, engineer, CHU de Nice
• El Mai Mounir, PhD, engineer, CHU de Nice
• Delphine Buret, MsC, engineer, CNRS
• Elisa Allart, MsC, engineer, CNRS
• Agathe Debris-Cafort, MsC, engineer, CNRS
• Scarlette Cassal, MSc, engineer, CHU de Nice
• Erendira Vazquez-Salazar, technician, CHU de Nice

We focus on understanding and treating nephrotic syndrome in adults, particularly Membranous Nephropathy (MN) and Focal and Segmental Glomerulosclerosis (FSGS).

Under the leadership of Prof. Seitz-Polski, our research on MN explores how environmental factors like air pollution and toxic substances increase disease incidence by overactivating the Th17 immune response, and we work on optimizing rituximab therapy through personalized dosing algorithms.

Dr. Shkreli’s work on FSGS highlights the role of telomerase in kidney regeneration and disease progression, aiming to harness telomerase for repairing damaged podocytes and developing new therapeutic strategies.

Our lab is dedicated to improving lives through rigorous scientific inquiry and innovative treatments. Thank you for supporting our mission to advance kidney health.

In adults, Nephrotic syndrome are related to two main diseases: Membranous Nephropathy and Focal and Segmental Glomerulosclerosis. Our research focuses on two main areas:

Immunopathology and Immunotherapy of Membranous Nephropathy (Prof. Seitz-Polski)

Membranous Nephropathy (MN) is a rare autoimmune kidney disease, related to autoantibodies directed against podocyte antigens (PLA2R1 70% and THSD7A 3%). Membranous Nephropathy is the first cause of adult nephrotic syndrome. The disease evolution goes from chronic kidney failure to spontaneous remission, or persistent nephrotic syndrome. Prof. Seitz-Polski is head of the Rare Disease Reference for nephrotic syndrome since 2017 and developed 2 axes of research:

(i) Impact of the environment on the orientation of the immune response in MN patients

Membranous Nephropathy incidence has increased over the last 20 years and epidemiological studies highlighted an association between air pollution exposure and Membranous Nephropathy incidence. The team demonstrated that MN patients presented an imbalance in their cytokine profile in favor of the Th17 responses. Exposome analysis of MN patients demonstrated that patients living in areas with high particulate matter levels, or working in the construction sector (exposed to occupational toxic substances: asbestos, organic solvents) exhibited overactivation of the Th17 pathway. This result has been confirmed in the general population (n=314). Exposure of peripheral blood immune cells from MN patients to particulate matter induces the production of pro-inflammatory cytokines from Th17 pathway. We then developed a mouse model of MN to determine (i) whether particulate matter exposure triggers Th17-dependent tissue inflammation in mice and promote MN, (ii) how particulate matter exposure disrupts kidney podocytes (AIRGEM Project funded by ORKID and ANR AAPG 2024).

 (ii) Immunomonitoring and Immunotherapy

Rituximab, a monoclonal anti-CD20 antibody, is the first line therapy for MN patients. It targets B lymphocytes and induces a depletion of anti-PLA2R1 or anti-THSD7A antibodies achieving remission. Immunomonitoring of rituximab revealed that 40% of patients developed anti-drug antibodies, leading to resistance and relapse. Furthermore, residual rituximab dosing revealed that nephrotic patients had urinary drug loss leading to drug underdosing. In collaboration with the start-up Exactcure, the team has developed a predictive algorithm for the risk of rituximab underdosing, capable of predicting the dose of drug to administer. This algorithm will be validated in a randomized trial starting in 2024 (iRitux PHRC 2022).

Telomerase and adult stem cell homeostasis in Focal and Segmental Glomerulosclerosis (Dr. Shkreli)

Dr. Shkreli provided the first insights into the involvement of telomerase in nephrotic syndrome and regeneration and developed 2 axes of research:

(i) To promote regeneration in the adult mammalian kidney

Homeostatic renal filtration relies on the integrity of glomerular visceral cells called podocytes. These highly specialized cells are damaged in nephrotic syndrome. We found that telomerase serves critical functions in adult kidney regeneration. We indeed showed that endogenous telomerase is required for glomerular renewal following injury, and we found that a pulse of telomerase expression is sufficient to activate a progenitor cell population that clonally expend and repopulate the podocyte compartment. We are using in vivo approaches to unveil the origin of podocyte progenitor cells, and we aim to determine if and how these cells are deregulated in pathological conditions and during organismal aging.

(ii) Targeting telomerase functions in kidney disease

Analysis of telomerase overexpressing mice revealed its critical role in collapsing focal segmental glomerulosclerosis (FSGS), a proliferative kidney disease characterized by rapid progression to end-stage renal disease (ESRD). We are deciphering the molecular mechanisms targeted by telomerase and regulating its functions upon FSGS initiation and progression in order to find alternative therapeutic approaches.

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