Functional Outcomes of Radiation Exposure
- Develop functional assays to quantify LDR/LDRt effects
- Engineer in-house 3D tissue models to interrogate LDR/LDRt sensitivity in functional assays
- Use data generated by functional assays to help construct mathematical models of LDR response
Data generated thus far suggests homeostatic modulation may occur in areas such as skin integrity, immune signaling, and phenotypic conversion.
Data generated thus far suggests LDR regulates signaling pathways that are known to impact carcinogenesis and skin integrity. Advanced engineered 3D model systems will be used to determine whether these signals are mitigated by normal homeostatic control mechanisms with the long-term objective of identifying those signals with the potential to functionally contribute to pathophysiology.
One example of how molecular responses are being bridged to tissue investigations include the recent identification of dynamic behavior in the extracellular signal regulated kinase (ERK) pathway by multiple systems biology investigators at PNNL. Mathematical models have predicted that ERK should oscillate and this prediction was validated experimentally using experimental human cell systems (keratinocyte/mammary epithelial).
LDR inhibits ERK oscillations and we are using transcriptomic measurements to define gene signatures that are unique to ERK oscillations. Gene signatures will be used to predict the subset of biological processes that are 1) regulated by ERK oscillations, and 2) sensitive to LDR exposures. In turn, this information will be used to develop appropriate experimental designs to interrogate these responses in complex tissues.