The major focus of my laboratory is to understand the molecular pathogenesis of childhood onset nephrotic syndrome (NS) and ultimately identify novel and non-toxic therapeutic targets for the treatment of this common childhood kidney disease. In line with this broad goal, I have been examining the molecular causes of NS and other inheritable kidney conditions. In the last five years, my colleagues and I have identified novel loci and genes for FSGS variant of NS, a disease risk locus for steroid sensitive nephrotic syndrome (SSNS) and a new gene for vesicoureteric reflux[VUR] (a common congenital malformation of the kidney and the urinary tract)(1,2,3).
FSGS constitutes an important cause of end stage kidney disease in children. The identification of the gene mutated in familial FSGS will improve our understanding of the pathogenesis of FSGS and identification of potential therapeutic targets. Dr. Gbadegesin and his colleagues recently identified the FSGS gene ANLN(3). ANLN encodes for anillin an F-actin binding protein that is important for cell division during development. Anillin function as a scaffold protein and it co-labels with key podocyte proteins, such as CD2AP and TRPC6. We have generated a WT anillin and mutant anillin cell line and demonstrated that the mutant cell line shows reduced binding to CD2AP, increased cell motility and activation of the PI3K/AKT pathway suggesting that mutant ANLN may cause FSGS by disorganization of the actin cytoskeleton and increased cell motility. We are currently using this cell line to study the effect of the mutations on critical pathways that are important for the maintenance of the glomerular filtration barrier (GFB). Working with collaborators around the world, Dr Gbadegesin is building a robust biorepository bank for further studies of molecular mechanisms of the more common idiopathic childhood nephrotic syndrome.