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 #
5U19AI067773-08
Application #
8382642
Study Section
Special Emphasis Panel (ZAI1-KS-I)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
8
Fiscal Year
2012
Total Cost
$436,606
Indirect Cost
$185,270
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Laiakis, Evagelia C; Mak, Tytus D; Strawn, Steven J et al. (2018) Global metabolomic responses in urine from atm deficient mice in response to LD50/30 gamma irradiation doses. Environ Mol Mutagen 59:576-585
Eppensteiner, John; Davis, Robert Patrick; Barbas, Andrew S et al. (2018) Immunothrombotic Activity of Damage-Associated Molecular Patterns and Extracellular Vesicles in Secondary Organ Failure Induced by Trauma and Sterile Insults. Front Immunol 9:190
Vera, Nicholas B; Chen, Zhidan; Pannkuk, Evan et al. (2018) Differential mobility spectrometry (DMS) reveals the elevation of urinary acetylcarnitine in non-human primates (NHPs) exposed to radiation. J Mass Spectrom 53:548-559
Lacombe, Jerome; Sima, Chao; Amundson, Sally A et al. (2018) Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: A systematic review. PLoS One 13:e0198851
Lee, Younghyun; Pujol Canadell, Monica; Shuryak, Igor et al. (2018) Candidate protein markers for radiation biodosimetry in the hematopoietically humanized mouse model. Sci Rep 8:13557
Rudqvist, Nils; Laiakis, Evagelia C; Ghandhi, Shanaz A et al. (2018) Global Gene Expression Response in Mouse Models of DNA Repair Deficiency after Gamma Irradiation. Radiat Res 189:337-344
Suresh Kumar, M A; Laiakis, Evagelia C; Ghandhi, Shanaz A et al. (2018) Gene Expression in Parp1 Deficient Mice Exposed to a Median Lethal Dose of Gamma Rays. Radiat Res 190:53-62
Zheng, Zhihong; Fan, Shengjun; Zheng, Jing et al. (2018) Inhibition of thioredoxin activates mitophagy and overcomes adaptive bortezomib resistance in multiple myeloma. J Hematol Oncol 11:29
Beach, Tyler A; Groves, Angela M; Johnston, Carl J et al. (2018) Recurrent DNA damage is associated with persistent injury in progressive radiation-induced pulmonary fibrosis. Int J Radiat Biol 94:1104-1115
Ghandhi, Shanaz A; Turner, Helen C; Shuryak, Igor et al. (2018) Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells. PLoS One 13:e0191402

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