Birth defects are a common problem that affect 3/100 of newborns, with the defects often being the result of abnormal development caused by genetic changes. Neonatal malformations of the kidney and the genitourinary system are particularly frequent (20-30% of all birth defects) and are responsible for 50% of pediatric end-stage kidney disease with a significant impact on life quality and life expectancy.
Multipotent progenitor populations in the developing kidney have the capacity to form all the physiologically mature cells that make up that adult kidney. The kidney controls homeostasis of the blood by controlling both blood pressure and filtration. Unwanted metabolites are excreted, and wanted compounds are recovered through specialized cell-types that begin to form during embryonic and fetal developmental stages. In the nephron alone, at least 23 different specialized cell types are present.
How these progenitor populations differentiate during development and generate this high order of cell-type diversity remains unknown, but with over 250 gene perturbations known to result in abnormalities to the development of the kidney and genitourinary tract, it is important to understand where these abnormalities arise and which cellular processes are perturbed.
The goal of our lab is therefore to understand how nephron cells generate mature cell types. These insights guide our work, developing strategies to recapitulate these cellular processes using stem cell-based organoid systems, which in turn result in high fidelity organoids that facilitate therapeutics for kidney disease.