Domestic security was radically and permanently changed by recent terrorist attacks. With these has come the sobering recognition that we are not adequately equipped to handle the detonation of a radiological dispersal device (RDD or so-called """"""""dirty bomb"""""""") or improvised nuclear device (IND). The development of rapid, minimally invasive biodosimetry that is field-deployable and reliable enough to guide decisions for the health care of populations exposed to multiple types of ionizing radiation under various conditions is a high priority. Our project addresses this priority and uses the powerful global profiling capabilities of metabolomics, a biomarker discovery platform uniquely suited for the analysis of biofluids such as blood and urine that require minimally- or non-invasive procedures to acquire. We have used metabolomics to define a urinary radiation response in mice and rats and are using these findings to guide discovery in humans. We propose to expand our research into more real-worid scenarios such as (1) low dose-rate exposures, (2) partial body exposures resulting from shielding of certain organs and tissues, (3) exposures to radioisotopes following an IND or RDD, and (4) mixed exposures to neutrons and low linear energy transfer (LET) radiation typical of an IND. We are also focusing attention on the development of prognostic biomarkers to predict individual outcomes from near lethal exposures as well as the mechanisms involved in biomarker responses. Our studies will be conducted using several inbred strains of mice as well as three genetically modified mouse strains, all of which have varying sensitivities to ionizing radiation. For comparison, human peripheral white blood cell samples will also be analyzed after ex vivo irradiation. Our approach is to harness the exquisite resolution and accurate mass measurement capabilities of the Ultra-Performance Liquid Chromatography-time-of-flight mass spectrometry metabolomics platform that has proven enormously useful to date. Our metabolomics analyses will be run in parallel with transcriptomics analyses (Project 2) and cellular endpoints (Project 1), sharing many of the same samples. Our goals are to define a strategy for minimally invasive biodosimetry for relevant real-worid radiation exposures and to find biomarkers by which the most severe radiation-related injuries may be identified as eariy as possible.

Public Health Relevance

A dirty bomb or improvised nuclear device could result in mass casualties from multiple types of radiation exposure and a need for rapid, high-throughput biodosimetry to guide treatment. By continuing to develop biodosimetry applicable to partial body, low dose-rate, internal emitters, and neutron exposures, and that indicate individual radiosensitivity, this project will address a critical need of national preparedness

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-KS-I (M1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
New York
United States
Zip Code
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

Showing the most recent 10 out of 185 publications