Our studies to date have laid the groundwork for applied gene expression biodosimetry, focusing on signature development for whole-body high dose rate external photon exposure. Other types of radiation exposures, including partial-body exposure, internal emitters, low dose rate, and neutron exposure, will also impact triage needs, and may produce distinct responses, or variations in the dosimetric signatures already identified. As estimates of dose provide only a general idea ofthe radiation injury expected across a population, it will also be important to develop signatures that may provide a more accurate prediction of radiation injury response and outcome on an individual basis. Project 2 will use a functional genomics approach to develop refined gene expression signatures of radiation exposure and dose addressing the two main renewal themes: first, the impact of different radiation modalities (partial-body exposure, internal emitters, low dose rate, and neutron exposure), and second, prediction of individual radiation sensitivity. Microarray analysis will be applied to human and murine samples to build upon the predictive signatures we have developed in the first funding period of this grant and to better adapt them to realistic radiation exposure scenarios. Mouse models will also be used to nvestigate the mechanistic underpinnings ofthe gene expression signatures that predict radiation dose and sensitivity. Project 2 will be tightly integrated with Projects 1 and 3 through the Irradiation Core (Core C), the Informatics Core (Core E), and through a sample sharing approach using both human blood irradiated ex vivo and in vivo irradiated mice. This sample sharing approach will also help to enable development by the Informatics Core of integrative analysis approaches spanning all three Projects and using data from the microRNA, mRNA, metabolomic, and cellular levels. Such an integrative approach will help provide mechanistic insight into the underpinnings of both transcriptomic and metabolomic signatures, as well as suggesting the best combinations of high-throughput biodosimetry assays to apply in specific practical scenarios.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI067773-09
Application #
8519237
Study Section
Special Emphasis Panel (ZAI1-KS-I)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
9
Fiscal Year
2013
Total Cost
$421,190
Indirect Cost
$117,976
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Laiakis, Evagelia C; Pannkuk, Evan L; Diaz-Rubio, Maria Elena et al. (2016) Implications of genotypic differences in the generation of a urinary metabolomics radiation signature. Mutat Res 788:41-9
Bertucci, Antonella; Smilenov, Lubomir B; Turner, Helen C et al. (2016) In vitro RABiT measurement of dose rate effects on radiation induction of micronuclei in human peripheral blood lymphocytes. Radiat Environ Biophys 55:53-9
Bian, Dakai; Tsui, Jason C; Repin, Mikhail et al. (2016) Liquid Handling Optimization in High-Throughput Biodosimetry Tool. J Med Device 10:0410071-4100710
Chen, Zhidan; Coy, Stephen L; Pannkuk, Evan L et al. (2016) Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry. J Am Soc Mass Spectrom 27:1626-36
Edmondson, David A; Karski, Erin E; Kohlgruber, Ayano et al. (2016) Transcript Analysis for Internal Biodosimetry Using Peripheral Blood from Neuroblastoma Patients Treated with (131)I-mIBG, a Targeted Radionuclide. Radiat Res 186:235-44
Lacombe, Jerome; Phillips, Shanna Leslie; Zenhausern, Frederic (2016) Microfluidics as a new tool in radiation biology. Cancer Lett 371:292-300
Ghandhi, Shanaz A; Smilenov, Lubomir B; Elliston, Carl D et al. (2015) Radiation dose-rate effects on gene expression for human biodosimetry. BMC Med Genomics 8:22
Goldman, Devorah C; Alexeev, Vitali; Lash, Elizabeth et al. (2015) The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice. Radiat Res 183:338-44
Sprung, Carl N; Ivashkevich, Alesia; Forrester, Helen B et al. (2015) Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects. Cancer Lett 356:72-81
Mak, Tytus D; Tyburski, John B; Krausz, Kristopher W et al. (2015) Exposure to ionizing radiation reveals global dose- and time-dependent changes in the urinary metabolome of rat. Metabolomics 11:1082-1094

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