Award
National Cancer Institute 5R35CA263778-05
Understanding and exploiting DNA topoisomerases in cancer biology
Recipient
Johns Hopkins University, Baltimore, MD, United States
Award Amount
$885,095.00
Ceiling
$885,095.00
Awarded
August 15, 2025
Identifier
5R35CA263778-05
This project focuses on type II DNA topoisomerases, crucial enzymes in cancer biology and drug targets. It aims to understand enzyme localization, drug specificity, and the impact of natural amino acid variation on topo II function, contributing to cancer etiology and treatment.
Description
Type II topoisomerases are molecular machines that untangle DNA and serve as targets of frontline anticancer drugs. The present proposal seeks to better understand and improve upon how anti-topoisomerase agents work; it will also determine how mutant topoisomerase variants, found in cancer cells, may contribute to genetic damage and chromosome instability. The project aims to deliver groundbreaking solutions to key problems in the field, including enzyme action, localization, and activity of topo II, as well as how amino acid sequence variation can destabilize human chromosomes and act as cancer drivers.