PRIMARY FACULTY
Vijay K. Singh, Ph.D.
Assistant Professor
Radiation Biology
4301 Jones Bridge Road
Bethesda MD 20814
Office: 301-295-2347
Fax: 301-295-6503
singh@afrri.usuhs.mil
Current goal of my laboratory is to elucidate the mechanism of action of radiation countermeasures at the cellular and molecular levels. At the cellular level, ionizing radiation produces breakage and cross linking of in DNA-proteins, cell membranes, and other macromolecular structures. At the organism level, the immediate effects of low-and moderate-intensity radiation are largely caused by cell death and the bystrander effects. At high doses hematopoietic and gastrointestinal (pictured) radiation syndromes are the cause of short-term radiation-induced lethality. We use various cellular and molecular immunology techniques for investigating different arms of the immune response to know the efficacy of radiation countermeasures. We are particularly interested in investigating cell signaling pathways such as cytokine expression, NF-?B stimulation, p53 pathway, and toll-like receptor activation. Recent studies demonstrated that radiation countermeasures such as tocopherol succinate, truncated flagellin (CBLB502), and mycoplasma lipopeptides (CBLB612 and CBLB613) stimulate high levels of G-CSF. CBLB502, CBLB612, and CBLB613 have been shown to activate NF-?B. The aim of cytokine investigation is to develop biomarkers for the drug efficacy, and understand the molecular mechanism of action of various radiation countermeasures. Stimulation of G-CSF by countermeasures leads to mobilization of progenitor cells, which protects animals after irradiation. We are interested for in vitro expansion of progenitors which can be used as mitigators for the effects of ionizing radiation. Our initial study demonstrates that myelod progenitors can be administered few days after irradiation, and this can increase the therapeutic window for the treatment. Our ultimate goal is to develop fieldable radiation countermeasures and understand mechanism of action so that agent can be made available for military and civilian use.
Recent Publications
- Singh VK, Grace MB, Jacobsen, KO, Chang CM, Parekh VI, Inal CE, Shafran RL, Whitnall AD, Jackson WE III, Whitnall MH: Cytokine expression after 5-androstenediol administration and gamma-irradiation in mouse hematopoietic tissues in vivo. Expt. Mol. Pathol. , 84:178-188, 2008.
- Srinivasan V, Doctrow S, Singh VK, Whitnall MH: Evaluation of EUK-189, a synthetic superoxide dismutase/catalase mimetic, as a radiation countermeasure. Immunopharmacol. Immunotoxicol. 30:271-290, 2008.
- Singh VK, Shafran RL, Jackson WE III, Seed TM, Kumar KS: Induction of cytokines by radioprotective tocopherol analogs. Expt. Mol. Pathol. 81:55-61, 2006.
- Kumar KS, Raghavan M, Hieber K, Ege C, Mog S, Parra N, Hildabrand A, Singh VK, Srinivasan V, Toles R, Karikari P, Petrovics G, Seed T, Srivastava S, Papa A: Preferential radiation sensitization of prostrate cancer in nude mice by nutraceutical antioxidants -tocotrienol. Life Sciences 78:2099-2104, 2006.
- Singh VK, Shafran RL, Inal CE, Jackson WE III, Whitnall MH: Effects of Whole-Body gamma Irradiation and 5-Androstenediol Administration on Serum G-CSF. Immunopharmacol. Immunotoxicol. 27: 521-534, 2005.
- Singh VK, Yadav VS: Role of Cytokines and growth factors in radioprotection. Expt. Mol. Pathol. 78: 156-169, 2005.
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