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Grant: Project Grant

University of British Columbia

$948,600.00

Identification of novel DNA nuclease inhibition strategies

FY 2025-26

Summary
The inhibition of proteins that work to repair damaged DNA has been an important contributor to cancer therapy. However, there is a lot of redundancy in how cells repair DNA, which can limit the effect of DNA repair inhibitors in cancer therapy. To overcome this redundancy, multiple proteins have to be inhibited simultaneously or a single protein can be inhibited in such a way as to block the activity of multiple repair proteins. To find blocking inhibitors, we have devised a new genetic method to identify and characterize protein targets that can block multiple repair pathways simultaneously. Here, we will use this approach to characterize a family of DNA repair proteins that are attractive anti-cancer therapeutic targets and work on designing chemical inhibitors. The project will explore a new approach to overcome the challenge of target redundancy in tumours and develop cross-acting inhibitors for a class of DNA repair proteins.
Program
Project Grant
Location
British Columbia, Canada
Recipient Type
Academia
Type
Grant
Source
CIHR Funding Decisions Database

As published

Id
532842
Name
Stirling Peter C
Region
British Columbia
Country
Canada
Orgtype
Research Institution; Institution Paid
Instname2
Genetics
Theme2
Biomedical
Prcname2
Genetics
Projecttitle
Identification of novel DNA nuclease inhibition strategies
Programtype2
Operating Grants
Orgnameinp2
University of British Columbia
Cihramount2
$948,600
Cihrequipment2
$0
Programname2
Project Grant
Keyworddelim
Cancer; Dna Damage; Dna Repair; Dna Replication; Dominant Negative; Homologous Recombination; Medicinal Chemistry; Nucleases; Small Molecule Inhibitors; Yeast
Abstract
The inhibition of proteins that work to repair damaged DNA has been an important contributor to cancer therapy. However, there is a lot of redundancy in how cells repair DNA, which can limit the effect of DNA repair inhibitors in cancer therapy. To overcome this redundancy, multiple proteins have to be inhibited simultaneously or a single protein can be inhibited in such a way as to block the activity of multiple repair proteins. To find blocking inhibitors, we have devised a new genetic method to identify and characterize protein targets that can block multiple repair pathways simultaneously. Here, we will use this approach to characterize a family of DNA repair proteins that are attractive anti-cancer therapeutic targets and work on designing chemical inhibitors. The project will explore a new approach to overcome the challenge of target redundancy in tumours and develop cross-acting inhibitors for a class of DNA repair proteins.
Competitiondate
202509
Approvedterm2
5 yrs 0 mth
Pinamesdelim
Stirling, Peter C
Approvedterm
5 ans 0 mois
Cihrcontribution2
~ $948,600~ $0~