Dr. Sally Amundson
Dr. Sally Amundson is an Associate Professor of Radiation Oncology and a faculty member of the Center for Radiological Research. A major project in her laboratory focuses on the development of biodosimetry to detect, measure, and monitor radiation exposure.
The Big Picture
As part of a national effort in emergency preparedness, Dr. Amundson’s laboratory is developing methods for estimating a person’s radiation dose after a large-scale radiological event. Such events could range from a power plant accident, like that at Fukushima, to a dirty bomb (conventional explosives used to blow up some radioactive material), or even the detonation of an improvised nuclear device. After such an event in a large city, many people would be worried that they had been irradiated. Having a quick way to determine how much radiation a person was exposed to will help to reassure the people who were not exposed. For people who were exposed, having an estimate of their radiation dose will help doctors to make sure they get the most appropriate treatment.
Radiation and Biodosimetry
Cells in the body respond to radiation exposure by triggering protective pathways and trying to repair damage or remove damaged cells. The effects of many of these responses can be measured in blood drawn from a vein in the arm, or even in a few drops from a finger prick. The white cells in blood are very sensitive to radiation exposure, and produce large changes in the expression of some of their genes to help them respond to radiation. The Amundson lab uses whole genome profiling techniques, like microarray analysis and RNA-Seq, to identify the most informative genes and study changes in their expression patterns under different radiation conditions. They are using these changes to develop gene expression signatures for biodosimetry.
Gene expression patterns or "signatures" are often shown as "heat maps". Here, each column represents an individual sample measured a day after radiation exposure, and each row represents one of 74 different genes. The samples are arranged in order of increasing dose, and by the colors we can see that for most of these genes, the higher the dose, the higher the level of expression.
To compare the differences in gene expression across an entire set of genes, multi-dimensional scaling can be used. In this example, all the information on expression of the 74 genes shown in Figure 1 has been used to determine mathematically how similar or different each sample was compared to the others. Each column from Figure 1 is now a single point. The closer together the points, the more similar the whole pattern of gene expression was for those samples. Here we see that different samples irradiated with the same dose are most similar to each other, and cluster together, while different doses are separated from each other.
The lab uses several different models for this work, including blood from patients undergoing radiotherapy, blood from healthy donors that is cultured and exposed to radiation in the lab, and mice that are exposed to radiation. By comparing results from all these models, we can start to understand how gene expression would respond to a certain dose of radiation if a healthy person were exposed. Ongoing experiments are also studying the effects of factors that could alter the gene expression profile, such as the time since exposure, how much of the body was exposed, how fast the dose was delivered, and what type of radiation was involved.
Finally, in order to make such a biodosimetry test practical for a large-scale triage situation, it needs to be very fast and easy to perform. The Amundson lab is collaborating with several groups with different approaches to move towards this goal. One approach focuses on collecting samples and sending them to large clinical labs that can already perform thousands of qRT-PCR measurements per day for other tests. The idea here is that if there is a radiological or nuclear emergency, these labs could switch over to measuring the radiation biodosimetry genes. A different approach is to develop self-contained microfluidic cassettes that could be used in the field where the blood samples are drawn. The blood could be drawn directly into such a device, and all the processing would be automated within the cassette, so that highly trained laboratory personnel would not be needed.
Early prototype of an integrated gene expression biodosimeter seen in a benchtop reader. The prototype was developed in collaboration with Dr. Frederic Zenhausern's group at the University of Arizona.
For more detailed descriptions of the research contact the Center for Radiological Research.