Multi-faceted approach for identifying biomarkers for radiation injury and regulatory approval of radiation medical countermeasures

Acute radiation syndrome (ARS) is caused by high doses of ionizing radiation (> 2 Gy). ARS is broken down into 3 sub-syndromes: exposure to 2–6 Gy results in hematopoietic ARS (H-ARS), exposure to 6–10 Gy results in gastrointestinal ARS (GI-ARS), and exposure to greater than 10 Gy results in neurovascular ARS (NV-ARS). In case of nuclear warfare events such as the bombings of Hiroshima and Nagasaki, or nuclear meltdown scenarios, such as Chernobyl and Fukushima-Daiichi, it is essential to be prepared to treat and prevent the development of ARS. Therefore, the development of prophylactic (administered before radiation exposure) and therapeutic (administered post-irradiation) radiation medical countermeasures (MCMs) is paramount in this effort. Currently, there are only 9 approved MCMs and all 9 are therapeutics for H-ARS. Thus, it is integral to develop a prophylactic MCM that treats high doses of radiation exposure injury. Following the Food and Drug Administration’s (FDA) animal rule, we are researching biomarkers of ARS to analyze whether prospective MCMs are effective in mitigating ARS development in humans. In this article, we summarize the various state-of-the-art omics platforms (metabolomics/lipidomics, proteomics, microbiome, and transcriptomics) which have been used to identify candidate biomarkers for acute radiation injuries using murine and nonhuman primate models. We have reviewed outside literature in addition to studies carried out in our laboratory.