Patrick Sung’s quest is to understand the processes by which cells repair DNA damage and then build on this knowledge to prevent and treat the cancers that can develop when such repairs fail.
Dr. Sung works with both yeast and human cells to understand the functions of DNA repair genes and to reconstitute DNA repair reactions with purified enzymes. His research focuses on the roles of the breast and ovarian tumor suppressors BRCA1 and BRCA2 in the repair process.
“This is fascinating work,” Dr. Sung said. “Once we understand protein action, we will be able to explain why cells become transformed and cancerous when DNA repair fails. While there are hundreds of BRCA1 and BRCA2 mutations, our experience allows us to zoom in on those we believe are the most deleterious and define their impact on the efficiency of DNA repair.”
The Sung laboratory has been able to prompt BRAC1 and BRAC2 genes to make proteins using a unique insect cell culture system. During cell division, the BRCA proteins enable cells to use the most accurate repair pathway. Without this help, cells use less accurate pathways, potentially leading to genetic mutations in DNA, chromosome rearrangements, genomic instability and, ultimately, cancer.
His team is developing chemical compounds to shut down the residual DNA repair capacity of cancer cells. The next step will be to evaluate potential efficacy of the most promising compounds using animal models and then working with medicinal chemists to make versions that are longer lasting in the body.
“Finally,” Dr. Sung added, “we hope to take the best candidates to clinical trials. It is a very long process, but the end result is so worthwhile.”