Models of Radiation Injury, Protection, Mitigation, and Therapy

TOPICAL COLLECTIONS

Guest Editors

Pradeep Kumar Shukla

University of Tennessee Health Science Center

Dr. Pradeep Kumar Shukla is currently working as an assistant professor (Physiology) at UTHSC, Memphis. He completed his PhD from Indian Institute of Toxicology Research, India. He haa eighteen years of research experience in neuroscience and gut physiology and his research focus lies in understanding the gut-brain interaction and its association with various neurological disorders. The gut-brain axis (GBA) establishes bidirectional communication between the central and the enteric nervous system, links emotional and cognitive centers of the brain with peripheral intestinal functions. Clinical evidence shows that microbiota mediated GBA interactions comes from the association of dysbiosis with central nervous disorders (i.e., autism, anxiety-depressive behaviors, alcohol liver disease) and functional gastrointestinal disorders. In particular, irritable bowel syndrome can be considered as an example of the disruption of these complex relationships, and a better understanding of these alterations might provide new targeted therapies.

Sue Chin Lee

University of Tennessee Health Science Center

Dr. Sue Chin Lee has been trained in lysophospholipid signaling as a graduate student at the Strathclyde Institute of Pharmacy and Biomedical Sciences. As a postdoctoral fellow at the University of Tennessee Health Science Center, she continued her research in lysophospholipid signaling with a specific focus on the roles of autotaxin (ATX) and the bioactive lipid lysophospholipid acid (LPA) in radiation injury and cancer. Her lab found that the upregulation of the ATX-LPA regulatory pathway is as an intrinsic defense mechanism that protects cells from genotoxic stress (i.e., induced by radiation or chemotherapy) by promoting DNA repair and cell survival. They hope that by identifying novel molecular targets that are key to initiating DNA repair or tissue regeneration could pave way for the development of drug candidates that mitigate radiation injury.

Collection Overview

Acute radiation syndrome (ARS) is a characteristic manifestation of g-radiation-induced poisoning. The source of ionizing g-radiation could come from accidental radiological exposure, nuclear attacks or from cancer associated radiotherapies. One of the most prominent symptoms of ARS is gastrointestinal disturbances such as vomiting, abdominal pain, mucosal inflammation, and diarrhea which lead to massive cell death in the intestinal epithelium, depletion of intestinal stem cell reserves that are critical for crypt regeneration, and breakdown of the intestinal barrier. High-dose radiation can also induce hematopoietic stem cell loss and immune suppression. In severe cases, this can result in septicemia and death. In the event that patients recover from ARS, they could potentially suffer from the long-term effects of radiation injury such as fibrosis and cancer. As a result, immense research efforts have been focused on understanding the mechanism by which high dose radiation induce short and long term tissue damage and the development of medical countermeasures (MCM) to negate these devastating effects. The field has primarily relied on ex vivo culture of mouse-derived intestinal stem cells or enteroid cultures, mouse models, and even non-human primates to study the clinical manifestation of radiation poisoning. More recently, human gut-on-a-chip cultures have also been used to study radiation induced injury and cell death. The goal of this collection is to share in-depth techniques and knowledge with the scientific community, standardize protocols for modeling radiation injury, and ultimately accelerate our progress in developing MCM.