Vijay Singh, Ph.D.

Vijay K. Singh, Ph.D.

Name: Vijay K. Singh, Ph.D.

USU Department of Primary Appointment: 
Pharmacology & Molecular Therapeutics
Title: 
Prof.
Faculty Rank: 
Full Professor
Location: 
Uniformed Services University of the Health Sciences, Bethesda, MD

Research Interests:
Radiation Biology
Countermeasures

Office Phone: 
(301) 295-2347

Education

1983 Ph.D., Central Drug Research Institute (KU), India
1978 M.Sc., Kanpur University, India
1975 B.Sc., Magadh University, India

Biography

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 investigating the mechanism of action of gamma-tocotrienol (GT3, an isomer of Vitamin E), Ex-RAD (a chlorobenzylsulphone derivative), toll-like receptor (TLR) ligands (CBLB502), and anti-ceramide antibody at the cellular level, by evaluating cell signaling pathways (cytokine expression, p53 pathway, TLR activation) including DNA damage and repair pathways.
In collaboration with corporate partners, my lab is developing several radiation countermeasures which are under advanced stages of development. CBLB502 and anti-cermide antibody appear to be promising. Ex-RAD has been shown to have both radioprotective 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 funding 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 radioprotective efficacy is mediated through G-CSF in murine model. 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 approved by US FDA, with full support. Based on the promising results of our pilot study using the large animal 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 had been supported by DMRDP (DoD). Additional countermeasures being investigated are CBLB612, CBLB613, and myeloid progenitors in collaboration with various academic and corporate partners with support from various funding agencies such as BARDA, NIAID, JPC7, CDMRP, and DMRDP.

Representative publications, projects, and/or deployments

  • G1B23687 Determination of radiation dose response for the AFRRI LINAC and subsequent non-clinical studies to evaluate potential medical countermeasures as mitigators of hematopoietic and/or low dose GI syndromes (H-ARS; GI-ARS) in an NHP model. Biomedical Advanced Research and Development Authority (BARDA), $8,535,865, September 15, 2015 – September 14, 2019
  • G1B22927 Advanced development of gamma-tocotrienol as a radiation countermeasure. Congressionally Directed Medical Research Programs (CDMRP), $7,811,978, September 21, 2015 – September 20, 2019.
  • G2B2HF Evaluation of radiation mitigators in nonhuman primates with supportive care. National Institute of Allergy and Infectious Diseases (NIAID), FY 2016 $406,581, FY 2017 $1,264,698, September 2015 – Sepetember 2017, Open ended, yearly renewal expected every year with additional budget.
  • NAB22586 Advanced development of Ex-RAD as a radiomitigator. Defense Medical Research and Development Program (DMRDP), $ 1,198,000, April 2014 – September 2017
  • G1B24024 Advanced Development of BIO 300 for Acute Radiation Syndrome and Delayed Effects of Acute Radiation Exposure, Congressionally Directed Medical Research Programs (CDMRP), $1,195,189, October 2016 – September 2019
  • RAB24402 Biomarkers for radiation injury: Integrative omics study, AFRRI, $240,000, November 11, 2016 – September 30, 2019
  • AFR-B2-4365 Development of Bio 301: An encapsulated nano-genistein therapy, Congressionally Directed Medical Research Programs (CDMRP), $712,295, POP to be negotiated

Bibliography

  • Singh VK, Seed TM: A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures. Int J Radiat Biol (in press: DOI: 10.1080/09553002.2017.1332438), 2017.
  • Singh VK, Garcia M, Seed TM: A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status. Int J Radiat Biol (in press: DOI: 10.1080/09553002.2017.1338782), 2017.
  • Singh VK, Hanlon BK, Santiago PT, Seed TM: A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part III. Countermeasures under early stages of development along with ‘standard of care’ medicinal and procedures not requiring regulatory approval for use. Int J Radiat Biol (in press: DOI: 10.1080/09553002.2017.1332440), 2017.
  • Fendler W, Malachowska B, Meghani K, Konstantinopoulos PA, Guha C, Singh VK, Chowdhury C: Evolutionarily conserved serum microRNAs can predict radiation-induced fatality in non-human primates. Sci Transl Med 9:eaal2408, 2017
  • Singh VK, Fatanmi OO, Wise SY, Newman VL, Romaine PLP, Seed TM: The potentiation of the radioprotective efficacy of two medical countermeasures, gamma-tocotrienol and amifostine, by a combination prophylactic modality. Radiat Prot Dosimetry 172:302-310, 2016.
  • Singh VK, Kulkarni S, Fatanmi OO, Wise SY, Newman VL, Romaine PLP, Hendrickson H, Gulani J, Ghosh SP, Kumar KS, Hauer-Jensen M: Radioprotective efficacy of gamma-tocotrienol in nonhuman primates. Radiat Res 185:285-298, 2016.
  • Krivokrysenko VI, Toshkov I, Gleiberman A, Krasnov P, Shyshynova I, Bespalov I, Maitra R, Narizhneva N, Singh VK, Whitnall MH, Purmal A, Shakhov A, Gudkov A, Feinstein E: TLR5 agonist Entolimod mitigates acute radiation syndrome in non-human primates. PLoS One 10:e0135388, 2015.
  • Elliott TB, Bolduc DL, Ledney GD, Kiang JG, Fatanmi OO, Wise SY, Romaine PLP, Newman VL, Singh VK: Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in mice exposed to radiation and combined injury. Int J Radiat Biol 91:690-702, 2015.
  • Dalgard CL, Jacobowitz DM, Singh VK, Saleem KS, Ursano RJ, Starr JM, Pollard HB: A novel analytical brain block tool to enable functional annotation of discriminatory transcript biomarkers among discrete regions of the fronto-limbic circuit in primate brain. Brain Res 1600:42-58, 2015.
  • Singh VK, Wise SY, Fatanmi OO, Scott J, Romaine PLP, Newman VL, Verma A, Elliott TB, Seed TM: Progenitors mobilized by gamma-tocotrienol as an effective radiation countermeasure. PLoS ONE 9:e114078, 2014.