Scientists in the Division of Immunology received a fouryear, $1.3 million grant from the National Institutes of Health to study a family of proteins involved in DNA repair. The research could improve radiation and chemotherapy cancer treatments.
|Yuan Chen is grappling with SUMO proteins.|
Small ubiquitin-like modifier (SUMO) proteins play key roles in many cellular functions. Though still not well understood, they also influence the repair of damaged DNA.
Normal, healthy cells need to repair their DNA if it becomes damaged, so much so that their survival depends on it. But DNA repair poses a problem when treating cancer.
“Radiation and many chemotherapy agents damage DNA; that’s how they kill cancer cells,” said Yuan Chen, Ph.D., professor of immunology and principal investigator for the project. “Unfortunately, as patients receive a number of courses of treatment, their cancer cells often become resistant to DNA damage.”
The resistant cancer cells then begin to grow again, and the disease returns.
Since SUMO proteins contribute to the DNA repair process, Chen believes they may
hold the key to overcoming resistance to chemotherapy and radiation. Previous work
in her laboratory has shown just that.
“We’ve already blocked SUMO proteins from binding to other proteins” in laboratory
cells, she explained. “These cells become more sensitive to DNA-damaging agents.”
Still, scientists must understand SUMO better before any specific treatments can be
devised, she said.
Chen, who joined City of Hope in 1994, has devoted much of her research focus to
understanding SUMO proteins and how they influence activities within the cell.
SUMO proteins act as connectors, joining together other important proteins that otherwise might not unite. Once connected, these proteins may be involved in any number of cell processes, including DNA repair.
Three SUMO proteins exist in human cells: SUMO1, SUMO2 and SUMO3. The latter two are twins; researchers refer to them collectively as SUMO2/3.
In the current project, Chen and her colleagues are trying to identify precisely how each SUMO protein is involved in DNA repair and which other proteins they bring together.
Once they identify the specific connections, Chen and her colleagues hope to identify or synthesize molecules that block DNA repair during chemotherapy and radiation. This would ensure no cancer cells escape therapy.
Chen noted that collaborations with Yun Yen, M.D., Ph.D., associate director for translational research in the cancer center, and David K. Ann, Ph.D., professor in the Department of Clinical and Molecular Pharmacology, have suggested a therapeutic connection. “That’s the next step,” Chen said. “Once we have results from this project, we can submit another grant to find or make SUMO inhibitors.”
Chen is collaborating with Jeremy Stark, Ph.D., assistant professor in the Department of Radiation Biology, and Terry D. Lee, Ph.D., professor in the Division of Immunology, on the project. Funding primarily comes from the National Institute of General Medical Sciences.