Research project
 

Telomerase and adult stem cell homeostasis

Marina SHKRELI, Researcher, CRCN Inserm
 

To promote regeneration in the adult mammalian kidney

Homeostatic renal filtration relies on the integrity of glomerular visceral cells called podocytes. These highly specialized cells are damaged in 90% of chronic kidney disease, representing the leading cause of end-stage renal failure. We found that telomerase serves critical functions in adult kidney regeneration. We indeed showed that endogenous telomerase is required for glomerular renewal following injury, and we found that a pulse of telomerase expression is sufficient to activate a progenitor cell population that clonally expend and repopulate the podocyte compartment. We are using in vivo approaches to unveil the origin of podocyte progenitor cells, and we aim to determine if and how these cells are deregulated in pathological conditions and during organismal aging.

 

Targeting telomerase functions in kidney disease

Analysis of telomerase overexpressing mice revealed its critical role in collapsing focal segmental glomerulosclerosis (FSGS) also known as collapsing glomerulopathy (CG), a proliferative kidney disease characterized by rapid progression to end-stage renal disease (ESRD). We are deciphering the molecular mechanisms targeted by telomerase and regulating its functions upon CG initiation and progression in order to find alternative therapeutic approaches for the treatment of CG.

Research teams