Studies of human population-scale genome-wide association studies (GWAS) found significant associations between genetic variants in Shroom3 and indicators of chronic kidney disease (CKD). Shroom3 is an actin-binding protein that regulates epithelial morphogenesis during kidney development. To date, we have found that Shroom3 was dynamically expressed in the embryonic and adult kidney, and that lack in functional Shroom3 leads to severe kidney developmental defects that culminate in adult-onset kidney disease.

ß-catenin is a transcription factor and cell adhesion molecule that acts as master regulator between different cell types in the kidney. In our laboratory, we have investigated ß-catenin’s expression and function in normal and dysplastic kidney tissue. We utilized conditional mutant mouse models, recapitulating the human condition, to investigate ß-catenin’s effect on nephrogenesis and branching morphogenesis. Our work has shown that ß-catenin is overexpressed in epithelium, mesenchyme and stroma of dysplastic kidney tissue, altering the fate of renal cell populations and contributing to the development of renal dysplasia.