Uniformed Services University
of the Health Sciences
Bldg. 42, 8901 Wisconsin Ave.
Bethesda, MD 20889-5603
Radiation Injury Combined
with Other Trauma Program
Juliann G. Kiang, PhD
My research interests are focused on the development of drugs and treatment approaches designed to prevent, mitigate, or reverse health damage resulting from exposure to ionizing radiation.
The potential for exposure to harmful doses of ionizing radiation exists in a wide variety of industries and professions. My effort to identify better radioprotectant drugs focuses on various signal transduction pathways activated by radiation, including the iNOS-caspases pathway, the iNOS-cytokines pathway, and the iNOS-autophagy pathway.
My previous studies showed that HSP-70 inducers and iNOS inhibitors effectively block hemorrhage-induced multiple organ dysfunction syndromes (MODS) and multiple organ failure (MOF), both of which employ biochemical pathways known also to be active in the response to radiation. We are investigating agents that induce HSP-70 and inhibit iNOS as potential countermeasure in a project supported by AFRRI intramural funding.
Radiation exposure combined with other trauma can occur under many of the circumstances. Irradiation combined with trauma such as wounding, burning, bleeding, hypoxia, or sepsis can produce synergistic effects greater than either injury alone. We are investigating radiation exposure combined with wound trauma in vivo and radiation exposure combined with hypoxia in vitro to understand why the augmentation occurs.
Using these models, we are exploring whether upregulation of HSP-70i and downregulation of iNOS can prevent, mitigate, or reverse combined injury. We are also investigating gene repair by ciprofloxacin that might block MODS and MOF. The combined injury project is supported by NIAID/NIH extramural funding. The route of radioprotectant drug administration and its timing is often critical for drug efficacy.
In mass-casualty situations where many people need to be treated promptly, timing and the route of administration can be a limiting factor. We are thus exploring the effectiveness of oral administration of radioprotectant drugs as well as intraperitoneal, subcutaneous, intramuscular, and intravenous injection based on patient-operated injector approaches. The project is supported by DTRA extramural funding.
- 2012—Kiang JG, Fukumoto R, Gorbunov NV. Lipid peroxidation after ionizing irradiation leads to apoptosis and autophagy. In: Angel Catala (ed.) Lipid Peroxidation; ISBN 980-953-307-143-0. InTech Open Access Publisher: www.intechweb.org. pp.261–278.
- 2012—Tsen SW, Wu TC, Kiang JG, Tsen KT. Prospects for a novel ultrashort pulsed laser technology for pathogen inactivation. J Biomed Sci. 2012 Jul 6;19(1):62. [Epub ahead of print]
- 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].
- 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. Page 23–44.
- 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.
- 2011—Kiang JG, Agravante NG, Smith JT, Bowman PD. 17-DMAG dimishes hemorrhage-induced small intestine injury by elevating Bcl-2 protein and inhibiting iNOS pathway, TNF-α increase, and caspase-3 activation. Cell & Bioscience 1:21.
- 2010—Daly MJ, Gaidamakova EK, Matrosova VY, Kiang JG, Fukumoto R, Wehr NB, Viteri G, Berlett BS, Levine RL. Small molecule proteome-shield in Deinococcus radiodurans. PLoS One 5(9):e12570.
- 2010—Gorbunov NV and Kiang JG. Response of crypt paneth cells in the small intestine following total-body gamma-irradiation. Intl J Immunopathol Pharmacol 23:1111–1123.
- 2010—Kiang JG, Garrison BR, Gorbunov NV. Radiation combined injury: DNA damage, apoptosis, and autophagy. Adapt Med 2:1–10.
- 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.
- 2009—Gorbunov NV, Kiang JG. Up-regulation of autophagy in small intestine Paneth cells in response to total-body gamma-irradiation. J Pathol. 219(2):242–252.
- 2009—Kiang JG, Smith JT, and Agravante NG. Geldanamycin analog 17-DMAG inhibits iNOS and caspases in gamma irradiated human T cells. Radiat Res 172: 321–330.
- 2008—Kiang JG, Krishnan S, Lu X, Li Y. Inhibition of inducible nitric oxide synthase protects human T cells from hypoxia-induced injury. Mol Pharmacol 73:738–747.