Kidney Development and Disease

Research

The Hohenstein lab studies the link between normal kidney development and kidney disease.

An important theme is the earliest events in the development of Wilms’ tumours, childhood kidney cancers that are the direct result of misdevelopment of the embryonic kidney. We and others have shown that the pre-MET nephron progenitor cells (NPCs) is the most likely stage of origin of these tumours.

Current research is focusing on the first two genes that were found mutated in Wilms’ tumours, WT1 and CTNNB1, the gene encoding β-catenin. We study how these genes control normal kidney development in different developmental stages, and how mutations in these genes disrupts normal development and can cause Wilms’ tumours, with a specific interest in the ΔS45 β-catenin mutation that is found in many Wilms’ tumours. We are interested in the developmental effects of these mutations, and in the molecular mechanism behind these phenotypes. This includes the direct effects of WT1 and β-catenin mutations on their own function, but also on pathways these genes interact with, and any other pathway or process in the developing kidney that might be affected. Of particular interest is the effect of WT1 and β-catenin mutations on the Wilms’ tumour cancer stem cells.

We are also interested in using our mutant models to develop high-throughput screens to identify therapeutic leads for new Wilms’ tumour drugs.

As much of our work on the origins of Wilms’ tumours provides new information on the normal control and behaviour of NPCs, we also hope to use this information and our models to improve regenerative medicine approaches for kidney replacement therapies.

Publications

Kidney development and disease research publications.

Tools and Technologies

In general, our projects are driven by our scientific questions, and we use whatever tools and techniques are required for that.