A5019073167- Parathyroid Disorders and Treatments
- Magnesium in Health and Disease
- Genetic Syndromes and Imprinting
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Genetic and Kidney Cyst Diseases
- Calcium signaling and nucleotide metabolism
- Neurological disorders and treatments
- Bone health and treatments
- CRISPR and Genetic Engineering
- Endoplasmic Reticulum Stress and Disease
Walter and Eliza Hall Institute of Medical Research
2023-2025
University of Zurich
2021-2024
Breakdown of mitochondrial proteostasis activates quality control pathways including the unfolded protein response (UPRmt) and PINK1/Parkin mitophagy. However, beyond up-regulation chaperones proteases, we have a limited understanding how UPRmt remodels restores damaged proteomes. Here, developed functional proteomics framework, termed MitoPQ (Mitochondrial Proteostasis Quantification), to dissect UPRmt's role in maintaining during stress. We find essential roles for both protecting...
The hormone fibroblast growth factor 23 (FGF23) controls phosphate homeostasis by regulating renal excretion. FGF23 acts on several transporters in the kidney. Here, we define time course of this action and demonstrate how NaPi-IIa NaPi-IIc are degraded.
Abstract The Calcium-sensing receptor (CaSR) senses extracellular calcium, regulates parathyroid hormone (PTH) secretion, and has additional functions in various organs related to systemic local calcium mineral homeostasis. Familial hypocalciuric hypercalcemia type I (FHH1) is caused by heterozygous loss-of-function mutations the CaSR gene, characterized combination of hypercalcemia, hypocalciuria, normal elevated PTH, facultatively hypermagnesemia mild bone mineralization defects. To date,...
Abstract Defects in neuronal mitophagy have been linked to neurodegenerative diseases including Parkinson’s disease. However, despite the importance of homeostasis, mechanistic basis for neurodegeneration when is defective unclear. Here, using human neurons, we discover that presynapses are pit stops damaged axonal mitochondria. We show while mitochondrial damage and PINK1/Parkin activation events distributed throughout axons, initiation autophagosome formation restricted presynapses, which...
Dietary inorganic phosphate (Pi) modulates renal Pi reabsorption by regulating the expression of NaPi-IIa and NaPi-IIc transporters. Here, we aimed to clarify role several Pi-regulatory mechanisms including parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) inositol hexakisphosphate kinases (IP6-kinases) in acute regulation NaPi-IIc.Wildtype (WT) PTH-deficient mice (PTH-KO) with/without inhibition FGF23 signalling were gavaged with Pi/saline examined at 1, 4 12 h.Pi-gavage...
Abstract The concentration of inorganic phosphate (Pi) in plasma is under hormonal control, with deviations from normal values promptly corrected to avoid hyper- or hypophosphatemia. Major regulators include parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23), and active vitamin D 3 (calcitriol). This control achieved by mechanisms largely dependent on regulating intestinal absorption renal excretion, whose combined actions stabilise Pi levels at around 1–2 mM. Instead,...
Consumption of phosphate-rich diets causes an adaptive response the body leading to urinary excretion phosphate. The underlying mechanisms are still poorly understood. Here, we examined role calcium-sensing receptor (CaSR) that senses both calcium and We confirmed increases secretion parathyroid hormone involved in stimulating phosphate excretion. However, did not find any evidence for a beyond this function.