Biomarker Core

Advances in molecular phenotyping technologies to measure inter-individual variations in genes, proteins, and metabolites have revolutionized precision medicine initiatives in radiation research. While the field has focused on the use of single omics to delineate biomarkers of radiation injury to X-rays or gamma rays; few have used a multi-omics for delineating biomarkers of exposures to neutrons or radiation at ultra-high dose rates (UHDR), both relevant for radiation exposures that occur with an improvised nuclear device (IND). The Biomarker Core will provide multi-omics services and technologies as a layered approach for the analyses of longitudinally collected biospecimens from rodent models of IND-relevant irradiations with or without mitigators, for gaining novel and holistic insights into pathway perturbations accompanying acute and delayed radiation response. The Biomarker Core team has been deeply engaged for over a decade in delineating biomarkers of radiation induced injury in heart and lung based on retrospective outcome analyses in mouse and rat models. The Core will leverage existing multi-omics-based biomarker panels that are predictive of radiation induced cardiac (CardioWatch) as well as lung injury in rodent models of X-ray exposure. Accordingly, the Biomarker Core will employ a set of multi-omics technologies including proteomics, metabolomics, and lipidomics, to assist MERIE research projects for molecular characterization of blood samples collected before, during, and after IND- relevant exposures. The Core will work closely with project leaders for discovery, verification and validation of biomarkers of radiation induced gastrointestinal injury (Project 1); lung injury (Project 2) and cardiac dysfunction (Project 3). The biomarker Core will also assist research projects to test the temporal pattern of biomarker expression following treatment with radiation mitigators of organ injury thus providing novel insights into pathway perturbations. Thus, the Biomarker Core will play an essential role in promoting the success of the MERIE center's overall research objectives to delineate the role of and efficacy of mitigators in reducing organ injury in rodent models of realistic IND exposures. The Biomarker Core will have two arms: The “Omics” arm will provide high-quality multi-omics data acquisition and deconvolution service, while the “Informatics” arm will leverage computational tools for predictive modeling for established biomarker panels as well as analyses and integration of multi-omics and multi-modal data to discern a systems level understanding of molecular responses to different types of IND exposures. The Biomarker Core will leverage the existing institutionally- supported shared resources at Georgetown University, with access to state-of-the-art instrumentation and tools for advanced informatics, data storage and computing resources with industry partners. All workflows will be informed by FDA guidelines for biomarker development and qualification. Completing this work in collaboration with project leaders will generate new knowledge of biomarkers and mechanisms underlying radiation response leading to organ injury.