Research Topics
Genomes and Genes | Gordon RuthelSummaryAffiliation: Walter Reed Army Medical Center Country: USA Publications
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Publications
Post-intoxication inhibition of botulinum neurotoxin serotype a within neurons by small-molecule, non-peptidic inhibitorsGordon Ruthel
U S Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702 USA
Toxins (Basel) 3:207-17. 2011..Taken together, the results indicate that competitive SMNPIs of BoNT/A light chain can be effective within neurons post-intoxication...
Time-lapse confocal imaging of development of Bacillus anthracis in macrophagesGordon Ruthel
Clinical Research Management, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702, USA
J Infect Dis 189:1313-6. 2004..By use of this method, we have determined that some phagocytized spores survive beyond germination, to become bacilli that then replicate within the macrophages...
Reduced expression of CD45 protein-tyrosine phosphatase provides protection against anthrax pathogenesisRekha G Panchal
United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702 5011, USA
J Biol Chem 284:12874-85. 2009..To date, this is the first report demonstrating that reduced levels of host phosphatase CD45 modulate anthrax pathogenesis...
Anthrax lethal toxin impairs innate immune functions of alveolar macrophages and facilitates Bacillus anthracis survivalWilson J Ribot
Target Identification and Translational Research, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702-5011, USA
Infect Immun 74:5029-34. 2006..Our data imply that cytolysis does not correlate with MEK1 cleavage, and this is the first report of LT-mediated impairment of nonhuman primate AM bactericidal activity against B. anthracis...
Antiviral activity of a small-molecule inhibitor of filovirus infectionTravis K Warren
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
Antimicrob Agents Chemother 54:2152-9. 2010..Taken together, these results identify a promising antiviral therapeutic candidate for the treatment of filovirus infections...
NKp30-dependent cytolysis of filovirus-infected human dendritic cellsClaudette L Fuller
United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA
Cell Microbiol 9:962-76. 2007..Further elucidation of the biology of NK cell activation, specifically natural cytotoxicity receptors like NKp30 and NKp46, promises to aid our understanding of microbial pathology...
Involvement of vacuolar protein sorting pathway in Ebola virus release independent of TSG101 interactionLynn S Silvestri
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21704, USA
J Infect Dis 196:S264-70. 2007..These data show that EBOV can use vps proteins independently of TSG101 for budding and reveal VPS4 as a potential target for filovirus therapeutics...
Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax pathogenesisKatherine C Brittingham
U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA
J Immunol 174:5545-52. 2005..Taken together, these results suggest that B. anthracis may exploit DCs to facilitate infection...
Chemical genetic screening identifies critical pathways in anthrax lethal toxin-induced pathogenesisRekha G Panchal
Target Structure Based Drug Discovery Group, SAIC Frederick, Inc, NCI Frederick, Frederick, Maryland 21702, USA
Chem Biol 14:245-55. 2007..Altering host responses through a chemical genetics approach can help identify critical cellular pathways involved in the pathogenesis of anthrax and can be exploited to further explore host-pathogen interactions...
Analysis of Ebola virus and VLP release using an immunocapture assayGeorge Kallstrom
Division of Virology, U S Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
J Virol Methods 127:1-9. 2005..Furthermore, this assay can be used in surrogate models in non-biocontainment environment, facilitating both basic research on the mechanism of EBOV assembly and budding as well as drug-discovery research...
Development of cell-based assays to measure botulinum neurotoxin serotype A activity using cleavage-sensitive antibodiesJonathan E Nuss
US Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702, USA
J Biomol Screen 15:42-51. 2010..Importantly, these assays provided novel methods for evaluating BoNT/A activity in cellular models of intoxication and allowed for the high-throughput evaluation of experimental compounds...
Development of high-content imaging assays for lethal viral pathogensRekha G Panchal
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA
J Biomol Screen 15:755-65. 2010..In conclusion, they show that image-based methods represent powerful screening tools for identifying antiviral compounds for highly pathogenic viruses...
Chemical modifications of antisense morpholino oligomers enhance their efficacy against Ebola virus infectionDana L Swenson
U S Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702, USA
Antimicrob Agents Chemother 53:2089-99. 2009..Conjugation with arginine-rich peptides greatly enhanced the antiviral efficacy of VP24-specific PMOs in infected cells and mice during lethal Ebola virus challenge...
A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloproteaseJames C Burnett
SAIC Frederick, Inc, Target Structure Based Drug Discovery Group, Frederick, Frederick, Inc, National Cancer Institute at Frederick, P O Box B, F V C 310, Frederick, Maryland 21702, USA
J Med Chem 50:2127-36. 2007..Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition...
Therapeutic inhibition of pro-inflammatory signaling and toxicity to staphylococcal enterotoxin B by a synthetic dimeric BB-loop mimetic of MyD88Teri L Kissner
Department of Immunology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America
PLoS ONE 7:e40773. 2012..Taken together, our results suggest that EM-163 exhibits a potential for therapeutic use against SEB intoxication...
Primary cultures of embryonic chicken neurons for sensitive cell-based assay of botulinum neurotoxin: implications for therapeutic discoveryAndrea M Stahl
U S Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702, USA
J Biomol Screen 12:370-7. 2007..Co-incubation of chick neurons with BoNT/A and toxin-neutralizing antibodies inhibited SNAP-25 cleavage, demonstrating the utility of these cultures for the assay of BoNT/A antagonists...
MyD88-dependent pro-inflammatory cytokine response contributes to lethal toxicity of staphylococcal enterotoxin B in miceTeri L Kissner
Department of Immunology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA
Innate Immun 17:451-62. 2011..This is due to the pro-inflammatory cytokine response elicited by MyD88 after exposure to SEB and LPS. These findings offer an important insight upon SEB intoxication and subsequent therapy targeting MyD88...
Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarizationMansour Mohamadzadeh
National Cancer Institute, Frederick, MD 21702, USA
Proc Natl Acad Sci U S A 102:2880-5. 2005....
Reduced levels of protein tyrosine phosphatase CD45 protect mice from the lethal effects of Ebola virus infectionRekha G Panchal
United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702 5011, USA
Cell Host Microbe 6:162-73. 2009..Together, these findings suggest that host susceptibility to EBOV is dependent on the delicate balance of immune homeostasis, which, as demonstrated here, can be determined by the levels of a single regulator...
A small molecule that mimics the BB-loop in the Toll interleukin-1 (IL-1) receptor domain of MyD88 attenuates staphylococcal enterotoxin B-induced pro-inflammatory cytokine production and toxicity in miceTeri L Kissner
Department of Immunology, Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702, USA
J Biol Chem 286:31385-96. 2011..Collectively, these results suggest that MyD88 BB-loop mimetics interfere with SEB-induced pro-inflammatory signaling and toxicity, thus offering a potential approach in the therapy of toxic shock...
Interleukin-15 increases vaccine efficacy through a mechanism linked to dendritic cell maturation and enhanced antibody titersKamal U Saikh
Department of Immunology, Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA
Clin Vaccine Immunol 15:131-7. 2008..This suggests a potential use of IL-15 as an adjuvant for antibody-dependent responses to vaccines...
Persistence of zinc-binding bacterial superantigens at the surface of antigen-presenting cells contributes to the extreme potency of these superantigens as T-cell activatorsDorothy D Pless
U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Frederick, MD 21702-5011, USA
Infect Immun 73:5358-66. 2005..Our findings suggest that the persistence of SEA and other zinc-dependent, cross-linking superantigens on the surface of antigen-presenting cells contributes to their potency as T-cell activators...
Activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by marburg and ebola virusesMansour Mohamadzadeh
U S Army Medical Research Institute for Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA
J Virol 80:7235-44. 2006..These data imply direct activation of TREM-1 by filoviruses and also indicate that neutrophils may play a prominent role in the immune and inflammatory responses to filovirus infections...
Efficacy of a capsule conjugate vaccine against inhalational anthrax in rabbits and monkeysDonald J Chabot
United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA
Vaccine 30:846-52. 2012....
Inhibition of metalloprotease botulinum serotype A from a pseudo-peptide binding mode to a small molecule that is active in primary neuronsJames C Burnett
Target Structure Based Drug Discovery Group, SAIC Frederick, Inc, Frederick, Maryland 21702, USA
J Biol Chem 282:5004-14. 2007..Isothermal titration calorimetry showed that the interaction between NSC 240898 and the botulinum A light chain is largely entropy-driven, and occurs with a 1:1 stoichiometry and a dissociation constant of 4.6 microM...
Association of ebola virus matrix protein VP40 with microtubulesGordon Ruthel
USAMRIID, 1425 Porter St, Frederick, MD 21702, USA
J Virol 79:4709-19. 2005..These results suggest that microtubules may play an important role in the Ebola virus life cycle and potentially provide a novel target for therapeutic intervention against this highly pathogenic virus...
Gaining ground: assays for therapeutics against botulinum neurotoxinRamin Mollaaghababa Hakami
Faculty Research Participation Program, Oak Ridge Associated Universities, Belcamp, MD, USA
Trends Microbiol 18:164-72. 2010....
In vitro inhibition of monkeypox virus production and spread by Interferon-βSara C Johnston
Virology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, Frederick, MD 21702, USA
Virol J 9:5. 2012....
Infectious Lassa virus, but not filoviruses, is restricted by BST-2/tetherinSheli R Radoshitzky
U S Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, Frederick, MD 21702, USA
J Virol 84:10569-80. 2010..Our results demonstrate that BST-2 might be a broad antiviral factor with the ability to restrict release of a wide variety of human pathogens. However, at least filoviruses, RVFV, and CPXV are immune to its inhibitory effect...
Human monocytes infected with Yersinia pestis express cell surface TLR9 and differentiate into dendritic cellsKamal U Saikh
U S Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA
J Immunol 173:7426-34. 2004..Our results suggest that increased expression of TLR9 on the surface of infected cells may serve a role as an activation signal to other cells of the immune system...
Ebola and Marburg virus-like particles activate human myeloid dendritic cellsCatharine M Bosio
Clinical Research Management, Frederick, MD 21702, USA
Virology 326:280-7. 2004..Thus, our findings suggest that unlike EBOV and MARV, VLPs are effective stimulators of DCs and have potential in enhancing innate and adaptive immune responses...
Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturationCatharine M Bosio
United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011, USA
J Infect Dis 188:1630-8. 2003..These findings may explain the profound virulence of EBOV and MARV--DCs are disabled, and an effective early host response is delayed by the necessary reliance on less-efficient secondary mechanisms...
In vivo oligomerization and raft localization of Ebola virus protein VP40 during vesicular buddingRekha G Panchal
Developmental Therapeutics Program, Target Structure Based Drug Discovery Group, Science Applications International Corporation, National Cancer Institute, Frederick, MD 21702 1201, USA
Proc Natl Acad Sci U S A 100:15936-41. 2003..We also report the successful application of the biarsenic fluorophore, FlAsH, combined with a tetracysteine tag for imaging of Ebola VP40 in live cells...
Nuclear export factor family protein participates in cytoplasmic mRNA traffickingIrina Tretyakova
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, NCI Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
J Biol Chem 280:31981-90. 2005..We propose a model in which MAP1B tethers the NXF-associated mRNA to microtubules and facilitates their translocation along dendrites while Unrip provides a scaffold for the assembly of these transport intermediates...
Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg virusesSina Bavari
Dept of Cell Biology and Biochemistry, U S Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702 5011, USA
J Exp Med 195:593-602. 2002....
