Vijay Singh, PhD

Assistant Professor
Radiation Biology
4301 Jones Bridge Road
Bethesda MD 20814
Office: 301-295-2347
Fax: 301-295-6503
singh@afrri.usuhs.mil
 

The 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 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.

Normal CD2F1 mouse jejunum compared to GI injury (200X) at 11 and 13 Gy (cobalt-60 gamma-radiation) at 4 day post-irradiation. As radiation dose increases there is an apparent a shortening of villi and loss of crypt of Lieberkühn.

At high doses, hematopoietic and gastrointestinal (illustrated, above) 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-κB 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-κB.

The aim of our cytokine investigation is to help develop biomarkers to improve 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 that can be used to mitigate the effects of ionizing radiation. Our initial study demonstrates that myelod progenitors administered a few days after irradiation can increase the therapeutic window for treatment.

Our ultimate goal is to develop fieldable radiation countermeasures and understand the mechanisms of action so that agents can be made available for military and civilian use.

Recent publications

  1. 2012—Singh VK, Christensen J, Fatanmi OO, Gille D, Ducey EJ, Wise SY, Karsunky H, Sedello AK. Myeloid progenitors: A radiation countermeasure that is effective when initiated days after irradiation. Radiat Res. 2012 May 4. [Epub ahead of print]
  2. 2012—Shakhov AN, Singh VK, Bone F, Cheney A, Kononov Y, et al. Prevention and mitigation of acute radiation syndrome in mice by synthetic lipopeptide agonists of Toll-like receptor 2 (TLR2). PLoS ONE 7: e33044. doi:10.1371/journal.pone.0033044.
  3. 2012—Singh VK, Ducey EJ, Brown DS, Whitnall MH. A review of radiation countermeasure work ongoing at the Armed Forces Radiobiology Research Institute. Int J Radiat Biol. 88:296–310. Epub 2012 Feb 9.
  4. 2012—Singh VK, Ducey EJ, Fatanmi OO, Singh PK, Brown DS, Purmal A, Shakhova VV, Gudkov AV, Feinstein E, Shakhov A. CBLB613: A TLR 2/6 agonist, natural lipopeptide of Mycoplasma arginini, as a novel radiation countermeasure. Radiat Res. 177:628–642. Epub 2011 Dec 16.
  5. 2012—Singh VK, Fatanmi OO, Singh PK, Whitnall MH. Role of radiation-induced granulocyte colony-stimulating factor in recovery from whole body gamma-irradiation. Cytokine. 58:406–414. Epub 2012 Apr 8.
  6. 2012—Singh PK, Wise SY, Ducey EJ, Fatanmi OO, Elliott TB, Singh VK. α-Tocopherol succinate protects mice against radiation-induced gastrointestinal injury. Radiat Res. 177:133–45. Epub 2011 Oct 20.
  7. 2012—Singh VK, Wise SY, Singh PK, Ducey EJ, Fatanmi OO, Seed TM. α-Tocopherol succinate and AMD3100-mobilized progenitors mitigate radiation-induced gastrointestinal injury in mice. Exp Hematol. 40:407–417. Epub 2012 Jan 10.
  8. 2011—Singh VK, Brown, DS, Singh, PK, Seed, TM. Progenitor cells as a bridging therapy for radiation casualties. Defence Science Journal 61: 118–124, 2011.
  9. 2011—Singh PK, Wise SY, Ducey EJ, Brown DS, Singh VK. Radioprotective efficacy of tocopherol succinate is mediated through granulocyte-colony stimulating factor. Cytokine. 56:411–421, 2011.
  10. 2011—Singh VK, Singh PK, Wise SY, Seed TM. Mobilized progenitor cells as a bridging therapy for radiation casualties: A brief review of tocopherol succinate-based approaches, Int Immunopharmacol. 11:842–47, 2011.
  11. 2011—Singh VK, Parekh VI, Brown DS, Kao TC, Mog SR. Tocopherol succinate: modulation of antioxidant enzymes and oncogene expression, and hematopoietic recovery, Int J Radiat Oncol Biol Phys. 79:571–8, 2011.
  12. 2010—Singh VK, Brown DS, Kao T-C. Alpha-tocopherol succinate protects mice from gamma-radiation by induction of granulocyte-colony stimulating factor, Int J Radiat Biol. 86:12–21, 2010.
  13. 2010—Singh VK, Brown DS, Kao T-C, Seed TM. Preclinical development of a bridging therapy for radiation casualties, Exp Hematol. 38:61–70, 2010.
  14. 2009—Singh VK, Brown DS, Kao T-C. Tocopherol succinate: A promising radiation countermeasure, Int Immunopharmacol. 9:1423–1430, 2009.
  15. 2009—Singh VK, Grace MB, Parekh VI, Whitnall MH, Landauer MR. Effects of genistein administration on cytokine induction in whole-body gamma-irradiated mice, Int Immunopharmacol. 9:1401–1410, 2009.
  16. 2008—Singh VK, Grace MB, Jacobsen KO, Chang CM, Parekh VI, Inal CE, Shafran RL, Whitnall AD, Kao TC, Jackson WE III, Whitnall MH. Administration of 5-androstenediol to mice: Pharmacokinetics and cytokine gene expression. Experimental and Molecular Pathology 84:178–188, 2008.
  17. 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.
  18. 2006—Singh VK, Shafran RL, Jackson WE III, Seed TM, Kumar KS. Induction of cytokines by radioprotective tocopherol analogs. Experimental and Molecular Pathology 81:55–61, 2006.
  19. 2006—Kumar KS, Raghavan M, Hieber K, Ege C., Mog S, Parra N, Hildabrand A, Singh V, Srinivasan V, Toles R, Karikari P, Petrovics G, Seed T, Srivastava S, Papas A (2006). Preferential radiation sensitization of prostate cancer in nude mice by nutraceutical antioxident gamma-tocotrienol. Life Sciences 78:2099–2104, 2006.
  20. 2006—Singh VK, Shafran RL, Jackson WE 3rd, Seed TM, Kumar KS. Induction of cytokines by radioprotective tocopherol analogs, Experimental and Molecular Pathology, 81:55–61, 2006.
  21. 2005—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. Immunopharmacology and Immunotoxicology 27:521–534, 2005.
  22. 2005—Singh VK, Yadav VS Role of cytokines and growth factors in radioprotection. Experimental and Molecular Pathology 78:156–169, 2005.
  23. 2005—Singh VK, Srinivasan V, Seed TM, Jackson WE, Miner VE, Kumar KS. Radioprotection by N-palmitoylated nonapeptide of human interleukin-1beta, Peptides 26:413–418, 2005.
  24. 2003—Kumar KS, Singh VK, Jackson W, Seed TM. Inhibition of LPS-induced nitric oxide production in RAW cells by radioprotective thiols, Exp Mol Pathol. 74:68–7, 2003.

Department Main Page

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AFRRI

Contact

Christopher R. Lissner, PhD, M(ASCP)
CAPT, MSC, USN Ret.
Scientific Director
Armed Forces Radiobiology Research
Institute & Acting Chair, Department
of Radiation Biology, School of Medicine,
Uniformed Services University
of the Health Sciences
Building 42, 8901 Wisconsin Avenue
Bethesda, Maryland 20889-5603
lissner@afrri.usuhs.mil
Tel 301-295-4995
FAX 301-295-4967


The image below is that of an announcement that appeared in Radiation Research, the official journal of the Radiation Research Society, for the USU PhD Program in Radiation Biology. Click the image to go to the home page of Radiation Research.

Radiation Research journal