The Kidney Foundation of Canada

Dr. Elena Torban 

Dr. Elena Torban

McGill University Health Centre Research Institute, Quebec

PCP effector Fuzzy in renal development and pathogenesis of CAKUT


2017-2019:  $100,000  |  Biomedical Research Grants  |  Category: Kidney Development

Biography

Dr. Elena Torban is an associate professor at McGill University and a basic scientist in the Division of Nephrology, McGill University Health Center. She received her PhD in kidney development at McGill and her post-doctoral training at the Montreal Neurological Institute and at McGill, where she studied the novel Planar Cell Polarity pathway in development. Dr. Torban’s current research focuses on the molecular and cellular mechanisms of congenital and acquired kidney disease. Congenital anomalies of the kidney and urinary tract (CAKUT) arise in 1 in 500 births and account for considerable morbidity in the pediatric population. Increasingly, CAKUT cases have been attributed to mutant genes, including those that encode proteins of primary cilia. In contrast, many diseases of the renal filtration apparatus reflect pathologies acquired throughout life. The overall objective of Dr. Torban’s research program is to identify and understand the pathomechanisms that underlie rare human kidney diseases, in order to develop new personalized therapies. Her lab is currently supported by the Kidney Foundation of Canada to study the role of Planar Cell Polarity genes in kidney development and renal cystic disease.

Lay Summary

In the Western world, between 2-6 out of every 1000 newborns are born with small kidneys and/or defects of the lower urinary tract– the compilation of diseases known as Congenital Anomalies of Kidney and Urinary Tract (CAKUT). In the most severe cases, kidneys are not formed at all; this condition is not viable. Even the milder congenital (developmental) defects are associated with progressive loss of kidney function, necessitating renal transplantations or urological surgeries. In Canada, the serious consequences of renal birth defects have doubled over the last 10 years. In order to understand the basis for these defects, it is important to decipher the molecular programs which regulate development of the kidneys and lower urinary tract.

In our laboratory, we recently discovered that a novel gene, Fuzzy, is crucial for normal renal development. When we generated transgenic mice lacking Fuzzy, we found that embryos had very small kidneys and ~ 15% of mutant embryos did not form kidneys at all. These data, for the first time, revealed that Fuzzy is a critical regulator of kidney formation. In this project, we propose to investigate how Fuzzy contributes to kidney development and how Fuzzy disruption leads to this severe kidney phenotype. We propose to combine the analysis of our mutant mice with studies of cultured cells derived from their tissues by immunofluorescence and other advanced methods. Based on preliminary data, we believe our studies will implicate Fuzzy into pathogeneses of CAKUT.