NARILIS lunch seminar | Prof. Alessandro Luciani, University of Zurich

We are pleased to invite you to a seminar given by

Prof. Alessandro Luciani ^PhD

Institute of Physiology, University of Zurich, Switzerland

Mechanisms of Inherited Kidney Disorders Group

His seminar is entitled

Unlocking Mechanisms and Therapeutic Paradigms for Rare Kidney Diseases

The epithelial cells lining the kidney's proximal tubule (PT) play a crucial role in maintaining homeostasis by efficiently reabsorbing small proteins and solutes through endocytosis and lysosome-related pathways. Disruptions in these core processes impair the tubule's homeostatic functions, leading to the leakage of low molecular weight proteins (LMWPs) and solutes into the urine, which can eventually contribute to kidney disease and life-threatening complications. Studies of rare inherited disorders affecting the proximal tubule have provided valuable insights into these fundamental pathways while identifying potential drug targets for therapeutic discovery and development. Using cystinosis as a paradigm of defective lysosomes leading to proximal tubulopathy, I describe signaling circuits that regulate homeostasis and the nutrient-seeking activities of tubular epithelial cells and how these processes can be disrupted in disease. Additionally, I highlight recent advances in preclinical model systems and present a conceptual framework leveraging cell- and lysosome-based functional assays, screening technologies, and digital tools to accelerate the discovery of therapeutic strategies tackling dysregulated homeostasis and proximal tubulopathy. These approaches hold promise not only for treating cystinosis but also for addressing other currently untreatable conditions, offering new opportunities to enhance health and homeostasis.

Read more :

• Berquez M, Chen Z, Festa BP, Krohn P, Keller SA, Parolo S, Korzinkin M, Gaponova A, Laczko E, Domenici E, Devuyst O, Luciani A. Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization. Nat Commun. 2023 Jul 14;14(1):3994.

• Luciani A, Devuyst O. The CTNS-MTORC1 axis couples lysosomal cystine to epithelial cell fate decisions and is a targetable pathway in cystinosis. Autophagy. 2024 Jan;20(1):202-204.

Invited by Prof. Thierry Arnould, UNamur, URBC