Rationale for Radiation Metabolomics
In order to prepare for the possible detonation of a radiological dispersal
device (RDD or so-called "dirty bomb"), improvised nuclear
device (IND), or radiological accidents, the development of rapid,
minimally invasive, and field-deployable biodosimetry is a high
priority. Our project addresses this priority with the powerful
global profiling capabilities of metabolomics, a biomarker discovery
platform uniquely suited for the analysis of easily accessible
biofluids, such as blood and urine, that require minimally- or
non-invasive procedures to acquire. We have established the field
of radiation metabolomics, and have published a series of seminal
papers on responses at the small molecule level after radiation.
Metabolomics has been used to define signatures of metabolites
in urine from mice, rats, non-human primates, and humans.
For more information, please visit the Fornace Lab website
What is radiation metabolomics?
The study and quantification of small molecules (<1kDa) in biofluids and tissues following exposure to ionizing radiation.
The use of global profiling technologies has contributed substantially
to the understanding of the radiation cellular stress response
and has contributed to the elucidation of many of the complex
biological networks associated with gene expression and signal
transduction. On a similar level, global understanding of how
ionizing radiation exposure affects small molecule concentrations
(such as metabolites) would be expected to lead to the identification
of metabolites that can be used to monitor for exposure and extent
of injury. Metabolomics is a rapidly advancing field that aims
to identify and quantify the concentration changes of all metabolites
(i.e., the metabolome) in a given biofluid or model system. In
order to assess the metabolic changes associated with ionizing
radiation exposure, our approach employs ultra-pressure liquid
chromatography (UPLC) coupled with highly sensitive time-of-flight
(TOF) mass spectrometry (MS) to profile small molecules (<1
kDa) from cultured cells, mice, and patient samples. We are utilizing
the Waters ACQUITY UPLC-TOFMS system and the Waters Xevo G2 QTOF
for metabolomic profiling of various easily accessible biofluids
(i.e. urine, blood), cells, and tissues. Quantification of the
validated metabolites is performed with the Waters Xevo TQ-S.
Putative biomarkers are picked utilizing statistical approaches
through chemometric software (SIMCA-P+ from Umetrics), Random
Forests through R, and in-house developed statistical software
(MetaboLyzer). The overall strategy is to develop metabolomic
signatures of radiation exposure using mouse models and to integrate
these results with those from patients undergoing total body irradiation.