Research Programs

• Focus on the customer—Through a broad-based, customer-oriented program, the Institute maintains the research program essential to the development of applications that meet the ever-changing needs of the military services. AFRRI addresses the services' requirements simultaneously from three perspectives: prevention of health hazards, assessment of biological damage, and treatment of injuries resulting from exposure to ionizing radiation alone or in combination with chemical or biological agents encountered on the battlefield.
• Military relevance—Advances in radioprotection strategies enable military forces to operate, when required, in nuclear or radioactive combat environments while minimizing both long- and short-term risks of the consequences of exposure to ionizing radiation. Accurate casualty prediction models promote effective command decisions and force structure planning. Advanced biological dosimetry methodology is used in triage, treatment decisions, and risk assessment. Together, the results of the three research thrusts improve therapeutic strategies for the treatment and prevention of early and long-term health effects and mitigate the risks to our personnel and their offspring.
• Unique contributions—In addition, AFRRI provides specialized expertise to evaluate and model radiological insults combined with other battlefield insults such as infection, disease, and biological warfare and chemical warfare agents. AFRRI acts as the catalyst, in collaborations with the worldwide scientific community, to publish medical and technical information based on data from nuclear accidents or incidents in other countries, including those in states of the former Soviet Union.
• Civilian applications—Humanity in general benefits from research and development in these areas; such developments are applicable to rescue operations involving, for example, terrorist actions or industrial nuclear accidents. The core competence in radiation biophysics and the technical database developed from AFRRI research are also applicable to astronauts exposed to space radiation.

• Countermeasure development—With an understanding of the mechanisms of radiation damage, AFRRI scientists are pursuing new and improved pharmacological approaches to prevent the life-threatening and health-degrading effects of ionizing radiation. Using novel cellular and molecular approaches and animal models, they move these potentially life-saving drugs from discovery through the Food and Drug Administration approval process.
• Assessing the risks—Accurate casualty prediction models promote effective command decisions and force structure planning. AFRRI research examines the impact of radiation injury combined with additional trauma, disease, chemical exposures, and other battlefield challenges. Investigations also assess the potential health effects of internal contamination and metal toxicity of militarily relevant metals that may become embedded as shrapnel, such as depleted uranium and tungsten alloys.
• Biological dosimetry—Scientists also seek to develop rapid, high-precision analytical methods that assess radiation exposure doses from clinical samples and thus aid in the triage and medical management of radiological casualties. Researchers are developing dose-assessment assays that test easily obtained samples such as a drop of blood, urine, or hair with transportable equipment. With innovative approaches, they also are improving the accuracy, dose range, ease of use, and speed of classical biodosimetry, which is based on cytogenetic damage.

• Biodosimetry
  1. DNA repair-gene expression to identify radiation exposure
     2012—Budworth H, Snijders AM, Marchetti F, Mannion B, Bhatnagar S, Kwoh E, Tan Y, Wang SX, Blakely WF, Coleman M, Peterson L, Wyrobek AJ. DNA repair and cell cycle biomarkers of radiation exposure and inflammation stress in human blood. PLoS One. 7:e48619.
  2. Identifying radiation biomarkers via mass-spectrometry metabolomics
     2012—Johnson CH, Patterson AD, Krausz KW, Kalinich JF, Tyburski JB, Kang DW, Luecke H, Gonzalez FJ, Blakely WF, Idle JR. Radiation Metabolomics. 5. Identification of Urinary Biomarkers of Ionizing Radiation Exposure in Nonhuman Primates by Mass Spectrometry-Based Metabolomics. Radiat Res. 178:328–340.
  3. Enhancing early-phase partial-body exposure assessment
     2011—Blakely WF, Sandgren DJ, Nagy V, Kim S-Y, and Ossetrova NI. Murine partial-body radiation exposure model for biodosimetry studies—Preliminary report. Radiat Meas. 46:898–902.
  4. Optimizing chromosome-aberration studies
     2011—Miura T, Blakely WF. Optimization of calyculin A-induced premature chromosome condensation assay for chromosome aberration studies. Cytometry A. 79(12):1016–22.
  5. Radiation-responsive proteins complement conventional biodosimetry
     2011—Ossetrova NI, Sandgren DJ, Blakely WF. C-reactive protein and serum amyloid A as early-phase and prognostic indicators of acute radiation exposure in nonhuman primate total-body irradiation model. Radiat Meas. 46(9):1019–1024.
  6. Applying the γ-H2AX assay to partial-body radiation exposure
     2011—Redon CE, Nakamura AJ, Gouliaeva K, Rahman A, Blakely WF, Bonner WM. Qγ-H2AX, an analysis method for partial-body radiation exposure using γ-H2AX in nonhuman primate lymphocytes. Radiat Meas. 46(9):877–881.
  7. Streamlining the dicentric chromosome assay
     2011—Romm H, Wilkins RC, Coleman CN, Lillis-Hearne PK, Pellmar TC, Livingston GK, Awa AA, Jenkins MS, Yoshida MA, Oestreicher U, Prasanna PG. Biological dosimetry by the triage dicentric chromosome assay: Potential implications for treatment of acute radiation syndrome in radiological mass casualties. Radiat Res. 175(3):397–404.
  8. Dynamic recording of radiation exposure data
     2010—Blakely WF, Madrid JP, Sandgren DJ. Biodosimetry medical recording—Use of the Biodosimetry Assessment Tool. Health Phys. 99 Suppl 5:S184–191.
  9. Discrimination of exposed vs. non-exposed individuals
     2010—Blakely WF, Ossetrova NI, Whitnall MH, Sandgren DJ, Krivokrysenko VI, Shakhov A, Feinstein E. Multiple parameter radiation injury assessment using a nonhuman primate radiation model—Biodosimetry applications. Health Phys. 98(2):153–9.
  10. Early assessment of radiation exposures
      2010—Ossetrova NI, Sandgren DJ, Gallego S, Blakely WF. Combined approach of hematological biomarkers and plasma protein SAA for improvement of radiation dose assessment triage in biodosimetry applications. Health Phys. 98(2):204–8.
      
      
• Countermeasure development
  1. Cellular therapies
     2012—Singh VK, Christensen J, Fatanmi OO, Gille D, Ducey EJ, Wise SY, Karsunky H, Sedello AK. Myeloid progenitors: A radiation countermeasure that is effective when initiated days after irradiation. Radiat Res. 177:781–791.
  2. Nutraceuticals as radioprotectants
     2012—Kulkarni SS, Cary LH, Gambles K, Hauer-Jensen M, Kumar KS, Ghosh SP (2012) Gamma-tocotrienol, a radiation prophylaxis agent, induces high levels of granulocyte colony-stimulating factor. Int Immunopharmacol. 14:495–503.
     2012—Singh VK, Singh PK, Wise SY, Posarac A, Fatanmi OO (2012) Radioprotective properties of tocopherol succinate against ionizing radiation in mice. J Radiat Res. 2012 Oct 3. [Epub ahead of print].
     2012—Satyamitra M, Ney P, Graves J, Mullaney C, V Srinivasan V. Mechanism of radioprotection by δ-tocotrienol: Pharmacokinetics, pharmacodynamics and modulation of signalling pathways. Br J Radiol. 2012 Jun 6. [Epub ahead of print].
     2012—Singh VK, Wise SY, Singh PK, Ducey EJ, Fatanmi OO, Seed TM. α-Tocopherol succinate and AMD3100-mobilized progenitors mitigate radiation-induced gastrointestinal injury in mice. Exp Hematol. 40:407–417.
  3. Cytokines and growth factors
     2012—Singh VK, Fatanmi OO, Singh PK, Whitnall MH. Role of radiation-induced granulocyte colony-stimulating factor in recovery from whole body gamma-irradiation. Cytokine. 58:406–414..
  4. Dual-use countermeasures for acute and delayed effects
     2011—Miller AC, Cohen S, Stewart M, Rivas R, Lison P. Radioprotection by the histone deacetylase inhibitor phenylbutyrate. Radiat Environ Biophys. 50:585–96.
  5. Animal models of radiation injury
     2011—Moroni M, Lombardini E, Salber R, Kazemzedeh M, Nagy V, Olsen C, Whitnall MH. Hematological changes as prognostic indicators of survival: Similarities between Gottingen minipigs, humans, and other
     large animal models. PLoS ONE. 2011;6:e25210. Epub 2011 Sep 28.
  6. Hematopoietic microenvironment mechanisms
     2012—Li XH, Ha CT, Fu D, Xiao M. REDD1 protects osteoblast cells from gamma radiation-induced premature senescence. PLoS ONE. 2012;7(5): e36604.
  7. Ex-RAD^®
     2012—Ghosh SP, Kulkarni S, Perkins MW, Hieber K, Pessu RL, Gambles K, Maniar M, Kao T-C, Seed TM, Kumar KS. Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RADR in mice. J Radiat Res. doi: 10.1093/jrr/rrs001.
  8. Toll-like receptor agonists
     2012—Krivokrysenko V, Shakhov A, Singh V, Bone F, Kononov Y, Shyshynova i, Cheney A, Maitra R, Purmal A, Whitnall M, Gudkov AV, Feiinstein E. Identification of G-CSF and IL-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation countermeasure. J Pharmacol Exp Ther jpet.112.196071; published ahead of print July 26, 2012, doi:10.1124/jpet.112.196071.
     2012—Singh VK, Ducey EJ, Fatanmi OO, Singh PK, Brown DS, Purmal A, Shakhova VV, Gudkov AV, Feinstein E, Shakhov A. CBLB613: A TLR 2/6 agonist, natural lipopeptide of Mycoplasma arginini, as a novel radiation countermeasure. Radiat Res. 177:628–642.
  9. 5-androstene steroids (first IND for an ARS countermeasure)
     2012—Grace MB, Singh VK, Rhee JG, Jackson WE III, Kao T-C, Whitnall MH. 5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis, J Rad Res. doi: 10.1093/jrr/rrs060.
  10. Effects of radiation quality on countermeasure efficacy
      2012—Cary LH, Ngudiankama BF, Salber RE, Ledney GD, Whitnall MH. Efficacy of radiation countermeasures depends on radiation quality. Radiat Res. 177:663–675.
      
      
• Internal contamination and metal toxicity
  1. Potential for wounds from embedded fragments of radioactive material
     2012—Emond CA, Kalnich JF. Biokinetics of embedded surrogate radiological dispersal device material. Health Phys., 102(2):124–136.
  2. Genetic damage to offspring from parent's exposure to DU
     2010—Miller AC, Stewart M, Rivas R. Preconceptional paternal exposure to depleted uranium: Transmission of genetic damage to offspring. Health Phys., 99(3):371–379.
  3. Assessing toxicity of metals and metal mixtures
     2009—Kane MA, Kasper CE, Kalinich JF. The use of established skeletal muscel cell lines to assess potential toxicity from embedded metal fragments. Toxicol In Vitro., 23(2):356–359.
  4. DNA methylation involvement in DU-induced leukemia
     2009—Miller AC, Stewart M, Rivas R. DNA methylation during depleted uranium-induced leukemia. Biochimie., 91(10):1328–1330.
  5. Health issues associated with newly developed munititions
     2009—Kane MA, Kasper CE, Kalinich JF. Protocol for the assessment of potential health effects from embedded metal fragments. Mil Med., 174(3):265–269.
  6. Determining radioactivity of shrapnel
     2008—Kalinich JF, Vergara VB, Emond CE. Urinary and serum metal levels as indicators of embedded tungsten alloy fragments. Mil Med. 173(8):754–758.
  7. Health effects of internalized tungsten
     2008—Kane MA, Kasper CE, Kalinich JF. The use of established skeletal muscle cell lines to assess potential toxicity from embedded metal fragments. Toxicol In Vitro., 23(2):356–358.
  8. Correlating DU exposure to specific health effects
     2007—Miller AC, McClain D. A review of depleted uranium biological effects: In vitro and in vivo studies. Rev Environ Health, 22(1):75–89.
  9. Shrapnel from tungsten alloy-based munitions
     2005—Kalinich JF, Emond CA, Dalton TK, Mog SR, Coleman GD, Kordell JE, Miller AC, McClain DE. Embedded weapons-grade tungsten alloy shrapnel induces metastatic high-grade rhabdomyosarcomas n F344 rats. Environmental Health Perspectives, 113(6):729–734, 2005.
  10. Pathogenesis of DU-induced leukemia
      2005—Miller AC, Bonait-Pellie C, Merlot R, Michel J, Stewart M, Lison P. Leukemic transformation of hematopoietic cells in mice internally exposed to depleted uranium. Molecular and Cellular Biochemistry, 279(1–2):97–104, 2005.
      
      
• Radiation injury combined with other trauma
  1. Wounding alters ionizing radiation dose assessment
     2012—Kiang JG, Garrison BR, Burns TM, Zhai M, Dews IC, Ney PH, Cary LH, Fukumoto R, Elliott TB, Ledney GD. Wound trauma alters ionizing radiation dose assessment. Cell Biosci. 2012 Jun 11;2:20. [Epub ahead of print]
  2. Role of sub-mucosal structures in the innate responses to infections
     2012—Gorbunov NV, Garrison BR, Zhai M, McDaniel DP, Ledney GD, Elliott TB, Kiang JG. Autophagy-mediated defense response of mouse mesenchymal stromal cells (MSCs) to challenge with Escherichia coli. In: Protein Interaction/Book 1; ISBN 979-953-307-577-7. Eds.: Cai J. InTech Open Access Publisher. Pages 23–44.
  3. 17-DMAG inhibits radiation-induced p53, improving survival
     2011—Fukumoto R, Kiang JG. Geldanamycin analog 17-DMAG limits apoptosis in human peripheral blood cells by inhibition of p53 activation and its interaction with heat shock protein 90 kDa after ionizing radiation. Radiat Res. 176(3):333–345.
  4. Efficacy of 17-DMAG at reducing hemorrhagic injury
     2011—Kiang JG, Agravante NG, Smith JT, Bowman PD. 17-DMAG diminishes hemorrhage-induced small intestine injury by elevating Bcl-2 protein and inhibiting iNOS pathway, TNF-alpha increase, and caspase-3 activation. Cell & Bioscience 1:21.
  5. Inactivating virus and bacterium with a visible femtosecond laser
     2011—Tsen KT, Tsen SW, Fu Q, Lindsay SM, Li Z, Cope S, Vaiana S, Kiang JG. Studies of inactivation of encephalomyocarditis virus, M13 bacteriophage, and Salmonella typhimurium by using a visible femtosecond laser: Insight into the possible inactivation mechanisms. J Biomed Opt. 16:078003.
  6. Using telemetry to monitor effects of irradiation
     2010—Carrier CA, Elliott TB, Ledney GD. Real-time telemetric monitoring in whole-body (60)Co gamma-photon irradiated rhesus macaques (Macaca mulatta). J Med Primatol. 39:399–407.
  7. D. radiodurans protects against extreme cellular insults caused by ionizing radiation
     2010—Daly MJ, Gaidamakova EK, Matrosova VY, Kiang JG, Fukumoto R, Lee DY, Wehr NB, Viteri GA, Berlett BS, Levine RL. Small-molecule antioxidant proteome-shields in Deinococcus radiodurans. PLoS One. 5(9). pii:e12570.
  8. Paneth cells linked to small-intestine inflammation post-irradiation
     2010—Gorbunov NV, Garrison BR, Kiang JG. Response of crypt paneth cells in the small intestine following total-body gamma-irradiation. Int J Immunopathol Pharmacol. 23:1111–1123.
  9. How combined injury modifies response to irradiation
     2010—Kiang JG, Garrison BR, Gorbunov NV. Radiation combined injury: DNA damage, apoptosis, and autophagy. Adaptive Medicine 2(1):1–10.
  10. Radiation combined injury delays wound-closure
      2010—Kiang JG, Jiao W, Cary LH, Mog SR, Elliott TB, Pellmar TC, Ledney GD. Wound trauma increases radiation-induced mortality by activation of iNOS pathway and elevation of cytokine concentrations and bacterial infection. Radiat Res. 173(3):319–332.
      
      

Within this track, students will learn the biology and physics of radiation. Building on a strong and broad basic science background, they will develop the research skills to address the growing scientific needs in radiation biology and develop an understanding of the policy context that is creating the renewed interest in this field.

The radiation biology faculty members are engaged in many exciting areas of research. They are exploring the mechanisms of injury from ionizing radiation in vitro and in vivo animal models, developing new approaches to prevent the life-threatening and health-degrading effects of ionizing radiation, and investigating biomarkers of injury that might be used to assess radiation exposure. The extensive radiation facilities housed at AFRRI can simulate almost any radiation exposure scenario in animal and cellular experiments.