Our laboratory has developed the minipig as an alternative large animal model for the Acute Radiation Syndrome (ARS) to test radiation countermeasures under the FDA animal rule. We are now interested in understanding common mechanisms of radiation injury across multiple animal models, as well as moderators of biological response that could explain differences in radiation sensitivity across species and strains. The ultimate goal is to provide evidence-based rationale for the selection of countermeasures to be tested in appropriate models.
Understanding the mechanisms of radiation injury is a prerequisite for the identification of effective and suitable countermeasures against the ARS. The current focus of the lab is the interplay among inflammation, coagulation, and disturbance of organ homeostasis. The complexity of the inter-relationship between organs and their regulatory feedback mechanisms has been so far largely neglected in the etiology of the ARS, while the main focus has been placed on recovery of bone marrow and mechanisms of cell death and proliferation. Indeed, the cross-talk among endothelium, inflammation, and coagulation plays a tremendous role in the etiology of human diseases, and is now recognized as the basis of organ failure in sepsis and diabetes.
We are seeking common mechanisms of radiation damage across multiple animal species and strains, with the implicit understanding that variations in the radiation sensitivity among individuals and models may emerge from moderators of the interaction between radiation and survival, instead of drastically different mechanisms of disease etiology.
Elliott T, et al: Natural History of Gastrointestinal Acute Radiation Syndrome in Gottingen Minipig (Sus Scrofa Domestica): An Exploratory Study. Comparative Medicine 64(6): 456-63, 2014
Moroni M, et al: Accelerated Hematopoietic Syndrome after Radiation Doses Bridging Hematopoietic (H-ARS) and Gastrointestinal (GI-ARS) Acute Radiation Syndrome: Early Hematological Changes and Systemic Inflammatory Response Syndrome in Minipig. International Journal of Radiation Biology 90(5): 363-72, 2014
Moroni M, et al: The Gottingen minipig is a model of the hematopoietic acute radiation syndrome: G-CSF stimulates hematopoiesis and enhances survival from lethal total-body gamma-irradiation. International Journal of Radiation Oncology Biology Physics 86(5): 986-992, 2013
Acute Radiation Syndrome; Animal models; Etiology; Physiology; Radiation sensitivity; Mechanisms; Countermeasures; Drug screening; FDA animal rule;