INDIANAPOLIS — An IUPUI researcher was awarded a $792,000, four-year grant from the American Cancer Society so that she can study the role of DNA replication errors in cancer.
Lata Balakrishnan, an associate professor of biology at IUPUI, will be using the grant to support her research to understand how regulatory processes ensure the accuracy of a cell’s DNA when it’s duplicated, and how the dysregulation of this process can lead to cancer. The dysregulation of DNA duplication is common in pancreatic cancer and blood cancers, including leukemia.
“Almost everyone knows someone who has been diagnosed with cancer,” Balakrishnan said in a press release. “Successful treatments make headlines since the impact on the patients is clear. However, to make these innovative therapeutic discoveries, we need to first understand specific biological processes within the cell and how dysregulation of these processes leads to development of diseases such as cancer.”
When a cell divides, the DNA code (also called “letters”) from the mother cell is duplicated, and one copy goes into each of the two daughter cells. This process is called DNA replication. Balakrishnan said genetic information is “constantly under attack” from different sources that change the DNA letters in genetic information. If the changes aren’t caught and corrected during a process called DNA repair, then the incorrect letter is copied.
Cells that divide more often are more susceptible to more errors, which increases the chance of cancer — as especially seen with how pancreatic and blood cancers have high rates of DNA replication errors.
“To better grasp this hugely complex process of DNA replication and repair within our cell, we need to study individual interactions between protein and DNA,” Balakrishnan said. “Understanding basic mechanisms in isolation gives us a better understanding of how a mutation either in the DNA or the protein can lead to the progression of diseases.”
Balakrishnan and her team will also test certain cancer drugs known as histone deacetylase inhibitors (HDACIs) in order to understand their impact on the efficiency of DNA replication and repair. Their goal is to understand multiple factors that contribute to the maintenance and reliability of the replication process.
“Our studies will provide valuable insight into how maintenance of the genome is impacted by altering cellular acetylation levels,” Balakrishnan said. “This knowledge can be harnessed to develop precision medicine targets for patients that have developed resistance to cancer treatments and can also be used for improving targeted therapies for a subset of cancers.”
Balakrishnan will collaborate with researchers from the IU Melvin and Bren Simon Comprehensive Cancer Center and the IU School of Medicine’s Proteomics Core Facility.