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Mechanisms and therapeutics of chronic kidney disease

Fabiola Terzi
Team description

Our team is dedicated to understanding and addressing the complexities of Chronic Kidney Disease. We aim to uncover the molecular mechanisms driving CKD progression, with a primary focus on developing novel therapies and identifying biomarkers to enhance patient care.

Chronic Kidney Disease (CKD) is a significant public health concern characterized by a gradual decline in renal function. Despite extensive efforts in the healthcare community, survival and quality of life for CKD patients remain a challenge, particularly due to an increased risk of cardiovascular disease. We also recognize the prevalence of CKD in kidney transplant patients, further highlighting the urgency to uncover the underlying mechanisms behind this relentless disease progression.

Experimental data show that reduced functional nephrons prompt compensatory growth to sustain kidney function. Yet, long-term adaptation strains remaining nephrons, causing stress and pathogenic changes, creating a destructive cycle. The rate of CKD progression hinges on nephrons' ability to handle stress. Identifying the molecular networks for initial compensation and lesion formation remains an ongoing pursuit.

Through our research, we aim to decipher the molecular mechanisms leading to CKD progression with a focus on four axes:

  1. The signaling pathways of CKD: EGFR pathway (with an emphasis on STK10), Hippo pathway (define the role of YAP/TAZ in glomeruli and tubules)
  2. LCN2 as a novel actor of CKD
  3. Primary cilia function in kidney mechano-surveillance and inflammation - Frank BIENAIME
  4. Clinical studies: validate CKD biomarker signature and define novel biomarkers of early graft damage

Our interdisciplinary team, composed of scientific investigators and physicians, fosters a continuous exchange of expertise, facilitating innovative research and advancements in kidney disease understanding. Our work is aimed at improving the lives of CKD patients and pushing the boundaries of medical science.

Key publications
Isnard P, Vergnaud P, Garbay S, Jamme M, Eloudzeri M, Karras A, Anglicheau D, Galantine V, Jalal Eddine A, Gosset C, Pourcine F, Zarhrate M, Gibier JB, Rensen E, Pietropaoli S, Barba-Spaeth G, Duong-Van-Huyen JP, Molina TJ, Mueller F, Zimmer C, Pontoglio M, Terzi F, Rabant M. A specific molecular signature in SARS-CoV-2-infected kidney biopsies. JCI Insight. 2023; Mar 8;8(5):e165192. doi: 10.1172/jci.insight.165192. PMID: 36749641 ; PMCID: PMC10077488.
Laouari D, Vergnaud P, Hirose T, Zaidan M, Rabant M, Nguyen C, Burtin M, Legendre C, Codogno P, Friedlander G, Anglicheau D, Terzi F. The sexual dimorphism of kidney growth in mice and humans. Kidney Int. 2022; Jul;102(1):78-95. doi: 10.1016/j.kint.2022.02.027. PMID: 35337891 .
Cohen C, Le Goff O, Soysouvanh F, Vasseur F, Tanou M, Nguyen C, Amrouche L, Le Guen J, Saltel-Fulero O, Meunier T, Nguyen-Khoa T, Rabant M, Nochy D, Legendre C, Friedlander G, Childs BG, Baker DJ, Knebelmann B, Anglicheau D, Milliat F, Terzi F. Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1. EMBO Mol Med. 2021; Nov 8;13(11):e14146. doi: 10.15252/emmm.202114146. PMID: 34725920 ; PMCID: PMC8573606.
Zaidan M, Burtin M, Zhang JD, Blanc T, Barre P, Garbay S, Nguyen C, Vasseur F, Yammine L, Germano S, Badi L, Gubler MC, Gallazzini M, Friedlander G, Pontoglio M, Terzi F. Signaling pathways predisposing to chronic kidney disease progression. JCI Insight. 2020; May 7;5(9):e126183. doi: 10.1172/jci.insight.126183. PMID: 32376805 ; PMCID: PMC7253021.
Yammine L, Zablocki A, Baron W, Terzi F, Gallazzini M. Lipocalin-2 Regulates Epidermal Growth Factor Receptor Intracellular Trafficking. Cell Rep. 2019; Nov 12;29(7):2067-2077.e6. doi: 10.1016/j.celrep.2019.10.015. PMID: 31722218 .