Department of Radiation Biology
Uniformed Services University
of the Health Sciences
Bldg. 42, 8901 Wisconsin Ave.
Bethesda, MD 20889-5603
Vijay K. Singh, PhD
Associate Professor and Acting Chair,
Department of Radiation Biology
Mechanism of radiation injury and advanced development of radiation countermeasures
My laboratory focuses attention on the molecular basis of radiation injury which results in acute radiation syndromes (ARS), and the mechanism of action of potential radiation countermeasures. Our ultimate goal is to develop radiation countermeasures to protect military personnel, first responders and civilians from succumbing to ARS following radiation exposure whether it is accidental or as a result of deliberate attack. To achieve this goal we are currently examining the mechanism of action of Ex-RAD (a chlorobenzylsulphone derivative), gamma-tocotrienol (GT3, an isomer of Vitamin E), toll-like receptor (TLR) ligands, and anti-ceramide antibody at the cellular level, by investigating cell signaling pathways (cytokine expression, p53 pathway, TLR activation) as well as DNA damage and repair pathways. In collaboration with Onconova Therapeutics my lab is developing Ex-RAD as a radiation countermeasure. Ex-RAD has been shown to have both radio protective and radiomitigative properties. Ex-RAD protects the hematopoietic system and is able to increase survival of irradiated mice by alleviating the severe radiation induced pancytopenia and restoring select bone marrow functions through the up-regulation of the PI3-kinase/AKT pathways and pathways involved with the DNA damage response and DNA repair. Ex-RAD studies have received significant fundings from DMRDP (DoD) and BARDA (HHS).
My lab is also working to develop GT3, as a radiation countermeasure in collaboration with Prof. Martin Hauer-Jensen. It has shown great promise in rodent model, capable of mobilizing progenitors, and its efficacy is mediated through G-CSF. Recently, we found that a single administration of GT3, without additional support (fluids, antibiotics, blood products, etc.), was just as effective as multiple administrations of G-CSF, the current gold standard of radiation countermeasures, with support. Based on the promising results of our pilot study using the NHP model, we have received funding from CDMRP (DoD) for the advanced development of GT3. Additionally, we are working to develop a novel anti-ceramide antibody in collaboration with Prof. Richard Kolesnick of Sloan Kettering and Ceramide Theraprutics as a radiation countermeasure, capable of being administered prior to or after radiation exposure. Studies have indicated that this potential countermeasure inhibits ceramide-mediated endothelial apoptosis, which provides significant protection against radiation induced, potentially fatal, gastrointestinal syndrome. Additional studies have shown that a single chain variable fragment of the full length antibody molecule is effective in doses one tenth of the full length version. This project has been supported by DMRDP (DoD). Additional countermeasures being investigated are CBLB502, CBLB612, CBLB613, 5-androstenedial, and myeloid progenitors in collaboration with various academic and corporate collaborators with support from various funding agencies.