Research

Congenital renal defects arise from disturbed kidney development

Kidney development is a complex process, which involves branching of the epithelial ureteric bud and induction of the adjacent metanephric mesenchyme. Defects in these processes result in congenital kidney malformations which may immediately require treatment (dialysis / transplantation) or increase risk for different diseases later in life.

The adult kidney, similarly to the nervous system and some other vital organs, fails to functionally regenerate. The embryonic kidney on the other hand, hosts progenitor populations, which are maintained as long as renal differentiation takes place. The two progenitor populations we are interested in are collecting duct and nephron progenitors. Their critical regulators, which guide self-renewal vs. differentiation decisions, are not fully identified. Moreover, the role of surrounding tissues, which form the stem cell niche, is only about to begin to be studied.

Rationale

The final nephron amount of an individual is defined during the embryonic life and it critically dictates renal health and function in adults. Congenitally reduced kidney size, which equals to diminished nephron mass, possess significant risk for e.g. renal and cardiovascular diseases as well as hypertension. Congenital renal defects are among the most common birth disorders that range from dysplasia to instantly life-threatening aplasia and pediatric cancer. The only treatments for these diseases are dialysis and transplantation.

The development of new therapeutic modalities for kidney diseases is largely hampered by a limited knowledge of the mechanisms regulating renal progenitor propagation and differentiation. The research of Kuure lab aims to provide crucial insight into these mechanisms with the specific intention that this information will significantly facilitate development of novel treatment strategies.

Ways to study kidney development

Kuure lab utilizes in vivo genetic engineering, live tissue imaging, call biology and systems biology approaches to reveal molecular signatures, metabolic requirements and cellular mechanisms of renal progenitor regulation. We aim to demonstrate how nephron progenitors interact with the surrounding niche to maintain stemness during nephrogenesis, and how changes in the biomechanical milieu of collecting ductal cells contribute to differentiation decision in branching epithelium.

Research topics

We are specifically interested in revealing how extracellular growth factor-stimulated intracellular pathways, such as mitogen-activated protein kinase (MAPK) pathway, are involved in the guidance of branching morphogenesis, regulation of stem and progenitor cell maintenance and their timely differentiation. It is expected that generating new models of congenital kidney defects that better phenocopy the given human disease, together with generally improved understanding of branching morphogenesis and nephrogenesis, will greatly facilitate early detection and potential prevention of renal diseases in future.