Grant: Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

McGill University

$0.00

A comprehensiveapproach to studygenetic causes ofchronic kidney disease

FY 2020-21

Summary

Chronic kidney disease (CKD) affects 1 in 10 Canadians. In 2015, more than 25,000 Canadians requiredtreatment with dialysis because of end stage kidney disease. Genetic causes of CKD are individually rare,yet their combined disease burden is significant (20% before age 20 and 10% in adults). Whole-exome-sequencing (WES) helped identify many genes which interact and converge on common CKD pathways,and genomic information has been shown to have direct treatment implications in patients with CKD.This offers hope for the development of novel personalized treatment strategies for patients with CKD.While WES is a comprehensive diagnostic approach, only 40-60% of the patients, who are believed tohave a genetic cause of CKD, receive a definitive molecular diagnosis. This is largely due to thecontinued discovery of mutations with uncertain impact on gene function, which presents a majorobstacle to the clinical utility of WES.I propose a comprehensive research program to systematically identify and functionally characterizenovel CKD genes and their mutations. In preliminary work, I used WES to identify autosomal recessivemutations in the TNS1 gene as a novel cause of proteinuric renal disease (Kitzler, ASN Kidney Week2019, Washington, DC). I will further study this gene by an approach combining WES data, patient-derived cell, and zebrafish animal models. This approach can be extended to other genetic causes ofCKD and the developed cell and animal models will enable me to perform high-throughput drugscreening for novel treatments of genetic kidney disease.The here proposed project will help establish a unique program in Canada for the elucidation of thepathophysiology of genetic kidney disease. It will improve the clinical utility of WES and lay thefoundation for the screening and development of novel targeted therapeutic strategies for patients withgenetic kidney disease.

Department

Canadian Institutes of Health Research

Program

Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

Recipient

McGill University

Location

Quebec, Canada

Recipient Type

Academia

Type

Grant

Source

CIHR Funding Decisions Database

As published

438804

Name

Kitzler Thomas M

Region

Québec

Country

Canada

Orgtype

Institution Paid; Research Institution

Partnername

Hospital for Sick Children Foundation

Prcname2

Special Cases

Projecttitle

A comprehensiveapproach to studygenetic causes ofchronic kidney disease

Programtype2

Operating Grants

Orgnameinp2

McGill University

Cihramount2

Cihrequipment2

Programname2

Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

Keyworddelim

Competitiondate

202007

Approvedterm2

3 yrs 0 mth

Pinamesdelim

Kitzler, Thomas M

Approvedterm

3 ans 0 mois

Abstract

<html> <head> </head> <body> Chronic kidney disease (CKD) affects 1 in 10 Canadians. In 2015, more than 25,000 Canadians requiredtreatment with dialysis because of end stage kidney disease. Genetic causes of CKD are individually rare,yet their combined disease burden is significant (20% before age 20 and 10% in adults). Whole-exome-sequencing (WES) helped identify many genes which interact and converge on common CKD pathways,and genomic information has been shown to have direct treatment implications in patients with CKD.This offers hope for the development of novel personalized treatment strategies for patients with CKD.While WES is a comprehensive diagnostic approach, only 40-60% of the patients, who are believed tohave a genetic cause of CKD, receive a definitive molecular diagnosis. This is largely due to thecontinued discovery of mutations with uncertain impact on gene function, which presents a majorobstacle to the clinical utility of WES.I propose a comprehensive research program to systematically identify and functionally characterizenovel CKD genes and their mutations. In preliminary work, I used WES to identify autosomal recessivemutations in the TNS1 gene as a novel cause of proteinuric renal disease (Kitzler, ASN Kidney Week2019, Washington, DC). I will further study this gene by an approach combining WES data, patient-derived cell, and zebrafish animal models. This approach can be extended to other genetic causes ofCKD and the developed cell and animal models will enable me to perform high-throughput drugscreening for novel treatments of genetic kidney disease.The here proposed project will help establish a unique program in Canada for the elucidation of thepathophysiology of genetic kidney disease. It will improve the clinical utility of WES and lay thefoundation for the screening and development of novel targeted therapeutic strategies for patients withgenetic kidney disease. </body> </html>

View source data CIHR Funding Decisions Database (Canadian Institutes of Health Research)