The overriding theme of this CMCR is ultra high-throughput biodosimetry. It is well established that this is a central and necessary component of any effective response to a large scale radiological-event. In the 4+ years that this CMCR program has been in existence, we have Achieved a biodosimetry sample throughput of 6,000 samples per day, and are on target for 30,000 samples per day in 2010. Throughputs with currently available standard biodosimetry approaches are typically <100/day. Demonstrated, for the first time, the ability of a single gene set to predict radiation dose, throughout a significant window of time post exposure, without the need for individual pre-exposure controls. Demonstrated the potential for a urine-based metabolomics biodosimetry system, with signals increasing in a dose-response manner, and with a signal lifetime of at least several days. Our initial application focused exclusively on external whole-body photon irradiation. One of the main themes of this renewal application is to assess the significance of the variety of other radiation scenarios that are likely to occur, in particular the effects of partial-body exposure, internal emitters, low dose rate, and neutron exposure. In that we have developed high-throughput systems for using various biomarkers for biodosimetry, we are now in a unique position to probe the application of these biomarkers for predicting inter-individual sensitivity to acute radiation syndromes. We have two interlaced motivations here;The first is to investigate correlations between our high-throughput biomarkers and individual acute radiation sensitivity, and the second is to probe the associated mechanisms. Both of these approaches build on - and would not be possible without - the high-throughput biodosimetry work that we have accomplished to date.

Public Health Relevance

A dirty bomb or improvised nuclear device could result in mass casualties from multiple types of radiation exposures, and there is thus a need for rapid, high-throughput biodosimetry to identify those who most require treatment. We will extend the high-throughput approaches that we have developed to date to be useful for partial body, low dose rate, internal emitter, and neutron exposures, and also for potentially identifying individuals with particular sensitivities to radiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
2U19AI067773-06
Application #
8008517
Study Section
Special Emphasis Panel (ZAI1-KS-I (M1))
Program Officer
Ramakrishnan, Narayani
Project Start
2005-08-31
Project End
2015-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
6
Fiscal Year
2010
Total Cost
$3,284,036
Indirect Cost
Name
Columbia University (N.Y.)
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Moquet, Jayne; Higueras, Manuel; Donovan, Ellen et al. (2018) Dicentric Dose Estimates for Patients Undergoing Radiotherapy in the RTGene Study to Assess Blood Dosimetric Models and the New Bayesian Method for Gradient Exposure. Radiat Res :
Cruz-Garcia, Lourdes; O'Brien, Grainne; Donovan, Ellen et al. (2018) Influence of Confounding Factors on Radiation Dose Estimation Using In Vivo Validated Transcriptional Biomarkers. Health Phys 115:90-101
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

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