Research Overview
The Muto Lab explores the gene regulatory mechanisms that govern kidney function in both health and disease. We are particularly interested in the interplay between metabolic and epigenetic alterations, which drives disease progression. Our lab employs a multidisciplinary approach, integrating cutting-edge wet-lab techniques with advanced computational analysis to uncover novel mechanisms of kidney disease and identify potential therapeutic targets.
We are currently focused on two major projects:
1. Amino Acid Metabolism and the AKI-to-CKD Transition
Acute kidney injury (AKI) is a frequent and severe complication, particularly among critically ill patients. Beyond its immediate effects, AKI significantly increases the risk of chronic kidney disease (CKD), a process known as the AKI-to-CKD transition. We and others have identified and characterized a pro-inflammatory, pro-fibrotic subset of proximal tubular cells, termed failed-repair proximal tubular cells (FR-PTC) that emerge following injury and may actively drive this transition. However, the mechanisms governing their persistence and pathological role remain poorly understood.
To address this, we have developed genetically engineered mouse models with dysregulated amino acid metabolism to investigate the molecular drivers of FR-PTC emergence and persistence. Using single-cell multi-omics and metabolomics, we aim to dissect the regulatory networks at play and uncover potential therapeutic strategies to mitigate CKD progression.
2. G-Protein-Coupled Receptors in Polycystic Kidney Disease (PKD)
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder, driven by mutations in PKD1 or PKD2 gene. It leads to progressive cyst formation, ultimately resulting in kidney failure. Despite advances in PKD research, the mechanisms governing cyst initiation and expansion remain poorly understood, limiting therapeutic development.
Through single-cell multi-omics analysis of both human and mouse ADPKD kidneys, we have identified a novel cyst marker: GPRC5A, an orphan G-protein-coupled receptor (GPCR) with previously unknown roles in PKD. Our research aims to Investigate its function using genetically engineered mouse models and multi-omics approaches.