William S. Dynan, Ph.D.
DNA is essential to the processes of life. But it can be damaged, and even break. When this happens, natural systems step in and conduct repairs.
William Dynan’s research is uncovering exactly how the body’s built-in repair machinery operates.
His lab focuses on one severe type of DNA damage: double-strand breaks, involving fractures to both strands of the double helix. Double-strand breaks can be caused by environmental factors, particularly ionizing radiation.
One of the key biochemical processes for repairing damaged DNA is called “non-homologous end joining,” or NHEJ. Dynan and his fellow researchers broke down the NHEJ process to its key biochemical components, then developed an in vitro method to replicate and study the same chemical system in the lab. They're also using mouse models to analyze NHEJ repair in the context of a living organism.
While it’s crucial to understand exactly how DNA repair machinery works, one of the biggest potential impacts of Dynan’s research is figuring out how to bring the repair process to a halt. The repair process is essential to human health, but there are instances where it’s helpful to turn it off — for example, in radiation therapy for cancer, one of the main topics of Dynan’s work.
If researchers could selectively inhibit DNA repair in tumor cells, this would reduce the tumor’s ability to fight back against radiation therapy — because those radiation-caused double-strand breaks would have no way to self-repair. Stopping the repair would make radiation therapy more effective while also limiting its negative effects on the patient. Currently, Dynan is investigating how to selectively inhibit a repair-associated gene called NONO to aid in treatment for melanoma.
A meticulously targeted DNA double-strand break also could be applied as gene therapy to prevent and eliminate a single-gene disorder like sickle-cell disease. The one harmful gene could be selectively damaged, and its ability to self-repair turned off.
As Dynan and his lab continue to piece together the complex system of DNA repair from its component parts, their work reveals new pathways toward these exciting potential therapies.
Dynan is also a participating researcher in a high-profile project funded by NASA, which brings together a team of Emory faculty to investigate how radiation exposure in space affects astronauts’ long-term health and cancer risks. Of particular concern are high-energy charged particles (HZE), a high-risk form of radiation. Dynan’s team is using CRISPR technology to analyze how exposure to HZE impacts DNA damage and repair.
A few of Dynan’s past and current contributions to the field include:
- Discovering Sp1 as a human promoter-selective transcription factor (1983).
- Discovering the Ku protein as the regulatory subunit of the DNA-dependent protein kinase (1992).
- Identifying a complex of NONO (p54nrb) and related protein SFPQ (PSF) as central to a non-canonical pathway of DNA double-strand break repair (2005).
Dynan was drawn to Emory for its world-class research programs investigating the biology of cancer. His joint appointment to the biochemistry and radiation oncology departments has supported interdisciplinary research with translational applications.