Biological effects of ionizing radiation
Ionizing radiation refers to X rays, γ-rays, energetic atomic nuclei, and other particles that have sufficient energy to break chemical bonds. Ionizing radiation deposits energy along discrete, nanometer-scale tracks. This pattern of energy deposition elicits double-strand breaks and other complex, difficult-to-repair DNA lesions. These lead to tissue damage, cancer, and likely premature aging.
The unique properties of ionizing radiation also allow it kill tumor cells, which are especially sensitive because they divide rapidly and because they often carry mutations that impair the ability to sense and respond to DNA damage.
The Dynan laboratory is known for its many contributions to understanding the biochemistry of DNA damage repair pathways and, previously, the biochemistry of RNA synthesis. The laboratory's work related to DNA repair has provided projects for more than 15 graduate students and postdoctoral fellows since 1995.
Research Projects
Recently the laboratory embarked on several new projects. One of these is a NASA-sponsored study of the health risks of galactic cosmic radiation. Galactic cosmic radiation, which consists primarily of high energy atomic nuclei, permeates the cosmos. It is a particular risk to deep space travelers who venture beyond the earth's protective atmosphere and magnetic field. Concerns over galactic cosmic radiation exposure are currently a limiting factor in the design of missions to the moon and Mars.
The current NASA study involves exposure of mice to simulated galactic cosmic radiation generated at a particle accelerator facility. The experiments are designed to reveal effects of dose, radiation type, and sex on the risk of development of lung and other cancers. The work also involves characterization of biomarkers of radiation exposure, validation of a form of vitamin B3 (nicotinamide riboside) as a radiation countermeasure, and the characterization of mutational signatures in radiation-induced lung cancer.
Other new work in the laboratory involves the characterization of exosomes secreted by irradiated cells and tumors. Exosomes are nanometer-size vesicles produced by cells and tissues following exposure to radiation or other stressors, or during senescence. Exosomes facilitate intercellular transport of RNAs, DNAs, proteins, and metabolites. Exosomes from irradiated tumor cells have a remarkable ability to promote host anti-tumor responses in a mouse model. The exosome work, which is in collaboration with Mohammad Khan, MD, is potentially relevant to treatment of melanoma and other cancers.