Laura Ewing, MS

Radiation-induced gastrointestinal syndrome (RIGS) is the primary factor limiting the dose-range and duration of radiotherapy treatment, leading to the cessation of treatment and poorer longterm outcomes. RIGS is exacerbated by various comorbidities, including poor diet, infections, inflammation, and genetic polymorphisms in DNA repair mechanisms. Radiation also affects the microbiome, favoring microbial populations that could produce infections or endotoxins. Even single dietary changes, such as supplementing methionine, exacerbate normal tissue toxicity and changes in gut ecology after radiation. Thus, this project proposes to study the mechanisms of toxicity underlying methionine supplementation, the microbiome, and the development of RIGS utilizing stereotactic body radiotherapy. To understand how methionine and disturbances in gut ecology alter the development of RIGS symptoms, a variety of novel techniques will be used, including next-generation and third-generation metagenomic, metatranscriptomic, and metabolomic approaches, to characterize microbial populations and methionine metabolism in internal organs before and after irradiation and under different doses of methionine. These data will be used to parameterize a computational model relating tissue concentration to external Met and radiation doses in mice to translate the findings to humans in order to develop mitigation strategies.