Ganesh Pathare

Bone-Kidney Axis and Regeneration Our lab investigates the bone–kidney axis and its role in kidney disease. We are also interested in harnessing this axis for regeneration to restore kidney function and mineral balance. The vertebrate endoskeleton not only supports locomotion but also regulates mineral and energy metabolism through constant cross-talk with the kidneys. The co-evolution of this bone-kidney axis enabled the development of calcium–phosphate-based skeletons, a crucial adaptation for terrestrial life. Central to this axis is the bone-derived hormone fibroblast growth factor 23 (FGF23) and its co-receptor Klotho, expressed in the kidney. Together, the FGF23–Klotho pathway regulates phosphate and vitamin D metabolism. Dysregulation of this pathway is now recognized as a potential driver of chronic kidney disease (CKD), which affects ~10% of humans and >40% of aging cats, making it a critical area of both human and veterinary health. Our research focuses on how disturbances in the FGF23–Klotho axis contribute to CKD progression and aging-like phenotypes, and on identifying strategies for therapeutic intervention. Fig.: Fig.: The FGF23–Klotho axis in mineral metabolism and CKD. FGF23 regulates phosphate and calcium balance by acting on the kidney through FGF receptors in the presence of Klotho. Dysregulation contributes to CKD–mineral bone disorder (CKD-MBD) and aging-related changes. We apply a multidisciplinary approach, combining genetically engineered mouse models, advanced in vitro assays, transcriptomics, single-nucleus RNA sequencing, human cohorts, and analyses of human urinary exosomes. Ongoing Projects: 1. Investigating mechanisms regulating FGF23 formation and its influence on bone remodelling. 2. Defining the segment-specific roles of Klotho in the renal tubules in health and CKD. 3. Developing therapeutic strategies to suppress FGF23-mediated ill effects in CKD and restore kidney function. 4. Exploring the role of the FGF23–Klotho axis in aging-like phenotypes and its relevance to human aging. The long-term goal of our research is to translate mechanistic insights from the bone–kidney axis into novel therapeutic strategies for CKD and age-related mineral disorders. These efforts aim to benefit both human and animal health, advancing the One Health initiative.

[May 2026] Bourqui, L., Trnjanin, A., Kopper, K., Loffing-Cueni, D., Radvanyi, Z., Karpovich, A., Rahimi, T., Santos, R., Wengi, A., Pastor, J., Moe, O. W., Loffing, J. (Co-last Author) & Pathare, G. (Co-last Author). Klotho in the kidney distal convolution regulates urinary Klotho excretion and kidney calcium reabsorption, but not phosphate homeostasis. Kidney International, 109(5), 987-1003, 17 p. [Sept 2026] Pathare, G., Loffing, J. & Moe, O. W. Authors’ response to “Reconsidering segment-specific Klotho regulation in renal mineral homeostasis”. Kidney International, 110(3), 736. [12 Mar 2026] Salas-Bastos, A. (Co-first Author), Bardet, C. (Co-first Author), Kopper, K., Jauze, L., Collaud, F., Francois, A., Moor, M. B., Chen, G., Mohammadi, M., Stockmann, C., Sommer, L., Loffing, J., Ro