Abnormal development of the kidney (renal dysplasia) can be the origin of various kidney diseases in children and adults. Our research aims at better understanding the pathogenesis of renal dysplasia by studying genetic pathways that regulate the complex cellular interactions involved in kidney development. Specifically, we are looking at two molecules, ß-catenin and shroom3, that are essential for kidney development and contribute to childhood and adult 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 are investigating ß-catenin's expression and function in normal and dysplastic kidney tissue. We utilize conditional mutant mouse models, recapitulating the human condition, to investigate ß-catenin's effect on nephrogenesis and branching morphogenesis. To date, 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.
Currently, we are investigating novel signaling pathways in order to identify genetic targets of ß-catenin in the cells of the kidney. Our recent findings suggest that shroom 3, an actin-associated protein important in epithelial morphogenesis, plays a role in kidney development. We 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.
The goal of our studies is to further elucidate the pathogenesis of renal dysplasia, thereby advancing knowledge required for the generation of new therapies for kidney disease.