Vijay K. Singh
Education1987 - 89 Visiting Associate, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
1984 - 87 Post-doctoral Fellow, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
1983 Ph.D., Central Drug Research Institute, Lucknow (KU), India
BiographyAdvanced development of radiation countermeasures: investigations for efficacy, identification and validation of biomarkers, mechanism of action, signal transduction
The primary research interests of my laboratory are to develop radiation countermeasures for acute radiation syndrome (ARS) following US FDA Animal Rule. My activities for this endeavor can be divided into the following major categories: 1) Development of genistein (isoflavone – BIO 300/BIO 301) as radiation countermeasure for ARS and delayed effects of acute radiation exposure (DEARE), 2) Development of Toll-like receptor (TLR) ligands (NF-kappaB stimulators: CBLB502, CBLB613, CBLB612), 3) Role of growth factors in progenitor mobilization and radiomitigation, 4) Identification and validation of biomarkers for radiation injury and countermeasure efficacy, 5) Advanced development of promising radiation countermeasures such as tocols (gamma-tocotrienol and related molecules), Ex-RAD, myeloid progenitors, anti-ceramide-antibody and other related agents using small and large animal models. My laboratory has extensive experience in studying the hematopoietic and gastrointestinal ARS following total-body and partial-body irradiation using animal models, and the effects of various radiation countermeasures on injury and recovery. My research focus is to identify and validate non-invasive biomarkers for radiation injury and countermeasure efficacy. I have extensively investigated several growth factors and cytokines/chemokines for mobilizing progenitors from bone marrow to peripheral circulation and radiomitigation. G-CSF is induced by several radiation countermeasures under development. These radiation countermeasures, by virtue of their ability to induce G-CSF, mobilize progenitors and in turn mitigate radiation injury.
My laboratory has identified and validated several biomarkers for radiation dose assessment, radiation injury, and efficacy of radiation countermeasures using various omic platforms. I have identified G-CSF, IL-6, several miRNAs, lipidomes, proteins, metabolites, and transcriptomes which can serve as biomarkers for radiation injury and countermeasure efficacy. I have also identified a few miRNAs which can distinguish irradiated versus unirradiated animals, and animals which will recover from radiation exposure vs. animals which will succumb to radiation injury. Similarly, there are a few miRNAs which can identify gender based mortality as a result of radiation injury. Furthermore, my group has identified a few lipidomes and metabolites which can help us identify different levels of radiation injury. We collaborates with large number of academic and corporate collaborators in US as well as from other countries.
I am recipient of several prestigious award and serving as editorial board member for few reputed journals and reviewer for large number of journals. I am also the reviewer for research grants of various US (specifically DoD, NASA, HHS) and international funding agencies. My research is supported by multiple research grant from DoD (JPC7, CDMRP, DMRDP, DTRA) and HHS (NIAID- NIH and BARDA).
Representative publications, projects, and/or deployments
May 2015 – Present: Professor (Tenured)
February 2013 – May 15: Associate Professor (Tenured)
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 30, 2021
Advanced development of -tocotrienol as a radiation countermeasure. Congressionally Directed Medical Research Programs (CDMRP), $7,811,978, September 21, 2015 – September 20, 2021
Evaluation of radiation mitigators in nonhuman primates with supportive care. National Institute of Allergy and Infectious Diseases (NIAID), FY 2015 $406,581, FY 2016 $1,226,757, FY17 $1,264,698, FY18 $725,333, FY19, $725,000, FY 20 $425,000, 9/30/2015 – 8/30/2021 (Open ended, yearly renewal expected every year with additional budget).
Advanced development of BIO 300 for acute radiation syndrome and delayed effects of acute radiation exposure, Congressionally Directed Medical Research Programs/Joint Program Committee 7 (CDMRP/JPC7), $1,195,189, October 2016 – September 2021
Development of Bio 301: An encapsulated nano-genistein therapy, Congressionally Directed Medical Research Programs (CDMRP), $712,295, 10/01/2018 – 09/30/2021.
Development of BIO 301 to prevent acute radiation syndrome and mitigate the delayed effects of acute radiation exposure. Congressionally Directed Medical Research Programs (CDMRP - JWMRP), $4,720, 276, 9/30/2019 – 9/29/2023.
Development of anti-ceramide scFv as mitigator of the radiation GI syndrome. National Institute of Allergy and Infectious Diseases (NIAID) SBIR phase 2, $1,350,000, 5/1/2019 – 4/30/2021
Biomarkers for the development of BIO 301 as a prophylactic radiation countermeasure for the acute and delayed effects of radiation exposure. Joint Program Committee-7, $1,089,459, 4/24/2020 – 4/23/2023
Cheema AK, Li Y, Girgis M, Jayatilake M, Fatanmi OO, Wise SY, Seed TM, Singh VK: Metabolomic studies in tissues of mice treated with amifostine and exposed to gamma-radiation. Metabolites 10:211, 2020
Cheema AK, Li Y, Girgis M, Jayatilake M, Simas M, Wise SY, Olabisi AO, Seed TM, Singh VK: Metabolomic studies in tissues of mice treated with amifostine and exposed to gamma-radiation. Scientific Reports 9:15701, 2019.
Pannkuk EL, Laiakis EC, Garcia M, Fornace Jr. AJ, Singh VK. Nonhuman primates with acute radiation syndrome: Results from a non-targeted serum metabolomics study after 7.2 Gy total body irradiation. Radiat Res 190:576-583, 2018.
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.