New England Regional Center of Excellence in Biodefense and Emerging Infectious D

Summary

Principal Investigator: Dennis L Kasper
Abstract: The New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (NERCE) has become a focal point for research and development in biodefense and emerging infectious diseases, developing novel approaches to treatment and prevention of infections. NERCE has supported and its core labs have been utilized by scientists from academia, the public health sector and the biopharmaceutical and biotechnology industries based in New England and across the country. The center functions as a catalyst for basic, translational and clinical research scientists to conduct research leading to new products directed against infectious disease. NERCE will continue this mission by supporting research addressing three primary themes - "Highly Pathogenic RNA Viruses", "Bacterial Toxins and other Pathogenic Proteins", and "Gram-Negative Bacteria - Pathogenesis and Immunity". The Center will continue its emphasis on "Chemical Biology" and high throughput approaches to experimental discovery. NERCE will also be supporting five core labs - "Microbiology and Animal Resources", "Biomolecule Production", "Small Molecule Screening", "Target Identification", and "Molecular Imaging". These core resources are available to the entire New England infectious disease community working on NIAID priority pathogens and agents of emerging infectious disease. The small molecule screening core (National Screening Laboratory for the Research Centers of Excellence in Biodefense and Emerging Infectious Diseases Research, or NSRB) supports scientists affiliated with any of the ten Regional Centers. NERCE will also continue its Developmental Projects program and Career Development in Biodefense program in an effort to initiate new research efforts and to attract new investigators to this field.
Funding Period: 2003-09-04 - 2015-02-28
more information: NIH RePORT

Top Publications

  1. pmc Nanowire-mediated delivery enables functional interrogation of primary immune cells: application to the analysis of chronic lymphocytic leukemia
    Alex K Shalek
    Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States
    Nano Lett 12:6498-504. 2012
  2. pmc A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals
    Manuel Garber
    Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Mol Cell 47:810-22. 2012
  3. ncbi Synthesis of pentasaccharides corresponding to the glycoform II of the outer core region of the Pseudomonas aeruginosa lipopolysaccharide
    Bozhena S Komarova
    Laboratory of Glycoconjugate Chemistry, ND Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia
    Carbohydr Res 360:56-68. 2012
  4. pmc Interspecies modulation of bacterial development through iron competition and siderophore piracy
    Matthew F Traxler
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    Mol Microbiol 86:628-44. 2012
  5. pmc Phenolic compounds as antiangiogenic CMG2 inhibitors from Costa Rican endophytic fungi
    Shugeng Cao
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Bioorg Med Chem Lett 22:5885-8. 2012
  6. pmc Critical phosphoprotein elements that regulate polymerase architecture and function in vesicular stomatitis virus
    Amal A Rahmeh
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 109:14628-33. 2012
  7. pmc Magic bullets for the 21st century: the reemergence of immunotherapy for multi- and pan-resistant microbes
    Damien Roux
    Division of Infectious Diseases, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    J Antimicrob Chemother 67:2785-7. 2012
  8. pmc Poly-N-acetylglucosamine expression by wild-type Yersinia pestis is maximal at mammalian, not flea, temperatures
    Pauline Yoong
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    MBio 3:e00217-12. 2012
  9. pmc Cytoskeleton assembly in Toxoplasma gondii cell division
    Brooke Anderson-White
    Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA
    Int Rev Cell Mol Biol 298:1-31. 2012
  10. pmc Role of interferon regulatory factor 7 in T cell responses during acute lymphocytic choriomeningitis virus infection
    Shenghua Zhou
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Virol 86:11254-65. 2012

Research Grants

Detail Information

Publications306 found, 100 shown here

  1. pmc Nanowire-mediated delivery enables functional interrogation of primary immune cells: application to the analysis of chronic lymphocytic leukemia
    Alex K Shalek
    Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States
    Nano Lett 12:6498-504. 2012
    ..Overall, our findings suggest a functional classification that can potentially guide the selection of patient-specific therapies in CLL and highlight the opportunities for nanotechnology to drive biological inquiry...
  2. pmc A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals
    Manuel Garber
    Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Mol Cell 47:810-22. 2012
    ....
  3. ncbi Synthesis of pentasaccharides corresponding to the glycoform II of the outer core region of the Pseudomonas aeruginosa lipopolysaccharide
    Bozhena S Komarova
    Laboratory of Glycoconjugate Chemistry, ND Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia
    Carbohydr Res 360:56-68. 2012
    ..Key features of the synthesis were two α-glucosylations with glucosyl donors bearing α-stereodirecting acyl groups at O-6 and/or O-3 and high-yielding reduction of the azido group followed by N-acylation and final O-debenzylation...
  4. pmc Interspecies modulation of bacterial development through iron competition and siderophore piracy
    Matthew F Traxler
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    Mol Microbiol 86:628-44. 2012
    ..AA4. Collectively these results suggest that competition for iron via siderophore piracy and species-specific siderophores can alter patterns of gene expression and morphological differentiation during actinomycete interactions...
  5. pmc Phenolic compounds as antiangiogenic CMG2 inhibitors from Costa Rican endophytic fungi
    Shugeng Cao
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Bioorg Med Chem Lett 22:5885-8. 2012
    ..The structure of the two new compounds, A (1) and B (2), were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments...
  6. pmc Critical phosphoprotein elements that regulate polymerase architecture and function in vesicular stomatitis virus
    Amal A Rahmeh
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 109:14628-33. 2012
    ..The functional interplay between these elements provides insight into the role of P as a dynamic player in the RNA synthesis machine, influencing essential aspects of polymerase structure and function...
  7. pmc Magic bullets for the 21st century: the reemergence of immunotherapy for multi- and pan-resistant microbes
    Damien Roux
    Division of Infectious Diseases, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    J Antimicrob Chemother 67:2785-7. 2012
    ..These discoveries could lead to utilization of antibodies to PNAG for either therapeutic use in patients infected by PNAG-producing MDR bacteria or prophylactic use in patients at risk of developing MDR infections...
  8. pmc Poly-N-acetylglucosamine expression by wild-type Yersinia pestis is maximal at mammalian, not flea, temperatures
    Pauline Yoong
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    MBio 3:e00217-12. 2012
    ..PNAG production by WT Y. pestis is maximal at mammalian and not insect vector temperatures, suggesting that this factor may have a role during mammalian infection...
  9. pmc Cytoskeleton assembly in Toxoplasma gondii cell division
    Brooke Anderson-White
    Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA
    Int Rev Cell Mol Biol 298:1-31. 2012
    ..Here, we review newly emerging insights in the prominent role that assembly of the cortical cytoskeletal scaffold plays in the process of daughter parasite formation...
  10. pmc Role of interferon regulatory factor 7 in T cell responses during acute lymphocytic choriomeningitis virus infection
    Shenghua Zhou
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Virol 86:11254-65. 2012
    ....
  11. pmc A Hendra virus G glycoprotein subunit vaccine protects African green monkeys from Nipah virus challenge
    Katharine N Bossart
    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA
    Sci Transl Med 4:146ra107. 2012
    ..Success of the recombinant subunit vaccine in nonhuman primates provides crucial data in supporting its further preclinical development for potential human use...
  12. pmc The first five seconds in the life of a clathrin-coated pit
    Emanuele Cocucci
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 150:495-507. 2012
    ..This objective picture of coated pit initiation also shows that methods outlined here will be broadly useful for studies of dynamic assemblies in living cells...
  13. pmc The NLRP12 inflammasome recognizes Yersinia pestis
    Gregory I Vladimer
    Division of Infectious Diseases and Immunology, UMass Medical School, Worcester, MA 01605, USA
    Immunity 37:96-107. 2012
    ..These studies reveal a role for NLRP12 in host resistance against pathogens. Minimizing NLRP12 inflammasome activation may have been a central factor in evolution of the high virulence of Y. pestis...
  14. pmc Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. V4
    Mohammad R Seyedsayamdost
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Chem Soc 134:13550-3. 2012
    ..These results highlight how modular siderophore gene clusters can be mixed and matched during evolution to generate structural diversity in siderophores...
  15. pmc Evaluation of the trimeric autotransporter Ata as a vaccine candidate against Acinetobacter baumannii infections
    Leticia V Bentancor
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Infect Immun 80:3381-8. 2012
    ..The ability of Ata to engender anti-adhesive, bactericidal, opsonophagocytic, and protective antibodies validates its potential use as an antigenic target against MDR A. baumannii infections...
  16. pmc TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria
    Vijay A K Rathinam
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Cell 150:606-19. 2012
    ..The identification of TRIF as a regulator of caspase-11 underscores the importance of TLRs as master regulators of inflammasomes during Gram-negative bacterial infection...
  17. pmc Immune evasion and recognition of the syphilis spirochete in blood and skin of secondary syphilis patients: two immunologically distinct compartments
    Adriana R Cruz
    Centro Internacional de Entrenamiento e Investigaciones Medicas, Cali, Colombia
    PLoS Negl Trop Dis 6:e1717. 2012
    ..The clinical syndrome associated with secondary syphilis (SS) reflects the propensity of Treponema pallidum (Tp) to escape immune recognition while simultaneously inducing inflammation...
  18. pmc Natural antibodies in normal human serum inhibit Staphylococcus aureus capsular polysaccharide vaccine efficacy
    David Skurnik
    Channing Laboratory, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Clin Infect Dis 55:1188-97. 2012
    ..aureus cell surface polysaccharide, poly-N-acetyl glucosamine (PNAG). Here we evaluated whether natural antibody to PNAG in normal human serum (NHS) had a similar deleterious effect...
  19. pmc Ifitm3 limits the severity of acute influenza in mice
    Charles C Bailey
    Department of Microbiology and Immunobiology, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts, United States of America
    PLoS Pathog 8:e1002909. 2012
    ..Collectively, these findings establish a central role for Ifitm3 in limiting acute influenza in vivo, and provide further insight into Ifitm3 expression and regulation...
  20. pmc Synthesis and evaluation of a conjugate vaccine composed of Staphylococcus aureus poly-N-acetyl-glucosamine and clumping factor A
    Tomas Maira-Litran
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 7:e43813. 2012
    ..In conclusion, ClfA is an immunogenic carrier protein that elicited anti-adhesive antibodies that fail to augment the OPK and protective activities of antibodies to the PNAG cell surface polysaccharide...
  21. pmc A Sendai virus-derived RNA agonist of RIG-I as a virus vaccine adjuvant
    L Martínez-Gil
    Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA
    J Virol 87:1290-300. 2013
    ..Our in vitro-transcribed DI RNA represents an excellent tool for the study of RIG-I agonists as vaccine adjuvants and a starting point in the development of such a vaccine...
  22. pmc A ribosome-specialized translation initiation pathway is required for cap-dependent translation of vesicular stomatitis virus mRNAs
    Amy Si Ying Lee
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 110:324-9. 2013
    ..Together, these findings demonstrate that the ribosome acts as a translational regulator outside of its catalytic role during protein synthesis...
  23. pmc Generating extracellular amyloid aggregates using E. coli cells
    Viknesh Sivanathan
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 USA
    Genes Dev 26:2659-67. 2012
    ..Furthermore, our findings establish the potential of this E. coli-based system to facilitate the implementation of high-throughput screens for identifying amyloidogenic proteins and modulators of amyloid aggregation...
  24. pmc Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1β
    Bibhuti B Mishra
    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Nat Immunol 14:52-60. 2013
    ..Our data indicate that the NO produced as a result of adaptive immunity is indispensable in modulating the destructive innate inflammatory responses elicited during persistent infections...
  25. pmc Identification of small molecules with type I interferon inducing properties by high-throughput screening
    Luis Martínez-Gil
    Department of Microbiology, Mount Sinai School of Medicine, New York, NY, USA
    PLoS ONE 7:e49049. 2012
    ..In addition, the IFN-inducing properties of C3 also suggest its potential use as vaccine adjuvant...
  26. pmc Cutting edge: FAS (CD95) mediates noncanonical IL-1β and IL-18 maturation via caspase-8 in an RIP3-independent manner
    Lukas Bossaller
    Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 189:5508-12. 2012
    ..Hence, Fas controls a novel noncanonical IL-1β activation pathway in myeloid cells, which could play an essential role in inflammatory processes, tumor surveillance, and control of infectious diseases...
  27. pmc Impact of anti-orthopoxvirus neutralizing antibodies induced by a heterologous prime-boost HIV-1 vaccine on insert-specific immune responses
    Stephen R Walsh
    Division of Infectious Diseases, Brigham and Women s Hospital, Boston, MA 02115, United States
    Vaccine 31:114-9. 2012
    ..The controls used in this study were the empty vectors (MVA and FPV)...
  28. pmc Identification of small molecules that suppress ricin-induced stress-activated signaling pathways
    Paul G Wahome
    Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America
    PLoS ONE 7:e49075. 2012
    ....
  29. pmc Characterization of 8-hydroxyquinoline derivatives containing aminobenzothiazole as inhibitors of dengue virus type 2 protease in vitro
    Huiguo Lai
    Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20057, USA
    Antiviral Res 97:74-80. 2013
    ..91±0.05μM was determined to be 2.36±0.13μM. This compound inhibits the DENV2 NS2B/NS3pro by a competitive mode of inhibition...
  30. pmc Antibody against TcdB, but not TcdA, prevents development of gastrointestinal and systemic Clostridium difficile disease
    Jennifer Steele
    Tufts Cummings School of Veterinary Medicine, Department of Biomedical Sciences, Division of Infectious Diseases, North Grafton, MA 01536, USA
    J Infect Dis 207:323-30. 2013
    ....
  31. pmc Dynamics of intracellular clathrin/AP1- and clathrin/AP3-containing carriers
    Comert Kural
    Department of Cell Biology, Harvard Medical School, Boston and Program in Cellular and Molecular Medicine at Boston Children s Hospital, Boston, MA 02115, USA
    Cell Rep 2:1111-9. 2012
    ..This observation suggests that an alternative budding mechanism, yet to be discovered, is responsible for the scission step of clathrin/AP1 and clathrin/AP3 carriers...
  32. pmc Old meets new: using interspecies interactions to detect secondary metabolite production in actinomycetes
    Mohammad R Seyedsayamdost
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    Methods Enzymol 517:89-109. 2012
    ..Here, we describe the detailed biological and chemical methods comprising these studies...
  33. pmc Opsonic and protective properties of antibodies raised to conjugate vaccines targeting six Staphylococcus aureus antigens
    Clarissa Pozzi
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    PLoS ONE 7:e46648. 2012
    ..Whereas each individual vaccine showed efficacy, combining antisera to CP antigens and PNAG still abrogated individual OPKA activities, indicating difficulty in achieving a multi-valent vaccine targeting both the CP and PNAG antigens...
  34. pmc A genome wide RNA interference screening method to identify host factors that modulate influenza A virus replication
    Christopher R Chin
    Microbiology and Physiological Systems Department, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Methods 59:217-24. 2013
    ..We find this approach to be readily implemented, scalable and amenable to the direct evaluation of a variety of viral lifecycles...
  35. pmc Targeted proteomic dissection of Toxoplasma cytoskeleton sub-compartments using MORN1
    Alexander Lorestani
    Department of Biology, Boston College, Chestnut Hill, MA 02467, USA
    Cytoskeleton (Hoboken) 69:1069-85. 2012
    ..Furthermore, we show that G-actin binding protein TgCAP is localized at the apical cap region in intracellular parasites, but quickly redistributes to a cytoplasmic localization pattern upon egress. © 2012 Wiley Periodicals, Inc...
  36. pmc Identification and evaluation of twin-arginine translocase inhibitors
    Michael L Vasil
    Department of Microbiology, University of Colorado School of Medicine, Aurora, CO, USA
    Antimicrob Agents Chemother 56:6223-34. 2012
    ..The compounds N-phenyl maleimide and Bay 11-7082 appear to directly affect TAT function based on this approach...
  37. pmc Chemoproteomic profiling identifies changes in DNA-PK as markers of early dengue virus infection
    Michael L Vetter
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    ACS Chem Biol 7:2019-26. 2012
    ..More broadly, these results highlight the utility of chemoproteomic profiling as a tool to detect changes in protein function associated with different cell states and that may occur on very short time scales...
  38. pmc Serine/threonine acetylation of TGFβ-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling
    Nicholas Paquette
    Division of Infectious Disease, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Proc Natl Acad Sci U S A 109:12710-5. 2012
    ..In addition, studies in mammalian cells show similar modification and inhibition of hTAK1. These data present evidence that TAK1 is a target for YopJ-mediated inhibition...
  39. pmc Preparation of unnatural N-to-N and C-to-C protein fusions
    Martin D Witte
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 109:11993-8. 2012
    ..Applied here to protein-protein fusions, the method reported can be extended to connecting proteins with any entity of interest...
  40. pmc Botulinum neurotoxin is shielded by NTNHA in an interlocked complex
    Shenyan Gu
    Center for Neuroscience, Aging and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 335:977-81. 2012
    ..These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics...
  41. pmc A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity
    Patrick Ymele-Leki
    Division of Infectious Diseases, Children s Hospital, Boston, Boston, Massachusetts, United States of America
    PLoS ONE 7:e31307. 2012
    ..This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples...
  42. pmc Borrelia burgdorferi requires the alternative sigma factor RpoS for dissemination within the vector during tick-to-mammal transmission
    Star M Dunham-Ems
    Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut, United States of America
    PLoS Pathog 8:e1002532. 2012
    ..Our data suggest that spirochetes default to an RpoS-independent program for round body formation upon sensing that the energetics for transmission are unfavorable...
  43. pmc Limited transferrin receptor clustering allows rapid diffusion of canine parvovirus into clathrin endocytic structures
    David K Cureton
    Immune Disease Institute and Program in Cellular and Molecular Medicine at Children s Hospital Boston, Boston, Massachusetts, USA
    J Virol 86:5330-40. 2012
    ....
  44. pmc Characterization of the 8-hydroxyquinoline scaffold for inhibitors of West Nile virus serine protease
    Manolya Ezgimen
    Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC 20057, USA
    Antiviral Res 94:18-24. 2012
    ..01 ± 0.08 μM using the tetra-peptide substrate was determined to be 5.8 μM. This compound inhibits the WNV NS2B/NS3pro by a competitive mode of inhibition which is supported by molecular modeling...
  45. pmc Host cell nucleolin is required to maintain the architecture of human cytomegalovirus replication compartments
    Blair L Strang
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Immune Disease Institute, Boston, Massachusetts, USA
    MBio 3:. 2012
    ..Nucleolin is, therefore, involved in the organization of proteins within replication compartments. This, to our knowledge, is the first report identifying a cellular protein required for maintaining replication compartment architecture...
  46. pmc The heterogeneous motility of the Lyme disease spirochete in gelatin mimics dissemination through tissue
    Michael W Harman
    Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030 3715, USA
    Proc Natl Acad Sci U S A 109:3059-64. 2012
    ..Our results also emphasize the importance of considering borrelial adhesion as a dynamic rather than a static process...
  47. pmc Genome-wide siRNA screen for mediators of NF-κB activation
    Benjamin E Gewurz
    Department of Medicine and Microbiology and Molecular Genetics, Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 109:2467-72. 2012
    ..Down-modulators of LMP1 mediated NFκB activation were also identified. These experiments identify multiple targets to inhibit or stimulate LMP1-, IL-1β-, or TNFα-mediated canonical NFκB activation...
  48. pmc Live-cell imaging of clathrin coats
    Comert Kural
    Department of Cell Biology, Harvard Medical School, and Immune Disease Institute and Program in Cellular and Molecular Medicine at Children s Hospital, Boston, Massachusetts, USA
    Methods Enzymol 505:59-80. 2012
    ....
  49. pmc An antibody recognizing the apical domain of human transferrin receptor 1 efficiently inhibits the entry of all new world hemorrhagic Fever arenaviruses
    Gustavo Helguera
    Departamento de Tecnologia Farmacêutica, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina
    J Virol 86:4024-8. 2012
    ..1 itself, can be broadly effective in treating South American hemorrhagic fevers...
  50. pmc Mechanism of RNA synthesis initiation by the vesicular stomatitis virus polymerase
    Benjamin Morin
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 31:1320-9. 2012
    ....
  51. pmc A novel strategy for development of recombinant antitoxin therapeutics tested in a mouse botulism model
    Jean Mukherjee
    Department of Biomedical Sciences, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America
    PLoS ONE 7:e29941. 2012
    ..This strategy should have widespread application in antitoxin development and other therapies in which neutralization and/or accelerated clearance of a serum biomolecule can offer therapeutic benefit...
  52. pmc Filoviruses require endosomal cysteine proteases for entry but exhibit distinct protease preferences
    JOHN MISASI
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts, USA
    J Virol 86:3284-92. 2012
    ..These studies strongly suggest that the use of endosomal cysteine proteases as host factors for entry is a general property of members of the family Filoviridae...
  53. pmc Evolutionary paths to antibiotic resistance under dynamically sustained drug selection
    Erdal Toprak
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Genet 44:101-5. 2012
    ..Sequencing of DHFR over the time course of the experiment showed that parallel populations evolved similar mutations and acquired them in a similar order...
  54. pmc Human cytomegalovirus UL44 concentrates at the periphery of replication compartments, the site of viral DNA synthesis
    Blair L Strang
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    J Virol 86:2089-95. 2012
    ..Our results reveal a previously unappreciated complexity of the organization of human cytomegalovirus replication compartments...
  55. pmc Ebola virus entry requires the host-programmed recognition of an intracellular receptor
    Emily Happy Miller
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
    EMBO J 31:1947-60. 2012
    ..NPC1 is the first known viral receptor that recognizes its ligand within an intracellular compartment and not at the plasma membrane...
  56. pmc Kinetics of proton transport into influenza virions by the viral M2 channel
    Tijana Ivanovic
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 7:e31566. 2012
    ..The saturating proton-concentration dependence and the low rate of internal virion acidification derived from authentic virions support a transporter model for the mechanism of proton transfer...
  57. pmc Architecture and regulation of negative-strand viral enzymatic machinery
    Philip J Kranzusch
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA
    RNA Biol 9:941-8. 2012
    ....
  58. pmc A Bacillus subtilis sensor kinase involved in triggering biofilm formation on the roots of tomato plants
    Yun Chen
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Mol Microbiol 85:418-30. 2012
    ..We propose that small signalling molecules released by the roots of tomato plants are directly or indirectly recognized by KinD, triggering biofilm formation...
  59. pmc Generation of thiocillin ring size variants by prepeptide gene replacement and in vivo processing by Bacillus cereus
    Albert A Bowers
    Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA
    J Am Chem Soc 134:10313-6. 2012
    ..Cyclization proceeds in many cases to provide altered ring sizes, giving access to several variant rings sizes that have not previously been observed in nature...
  60. pmc Protein thioester synthesis enabled by sortase
    Jingjing J Ling
    Department of Chemistry, Massachusetts Institute of Technology, 16 573a, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 134:10749-52. 2012
    ..We show that both variants can translocate through protective antigen pore. This new method to synthesize a protein thioester allows for interfacing of sortase-mediated ligation and native chemical ligation...
  61. pmc Development and characterization of a Pseudomonas aeruginosa in vitro coupled transcription-translation assay system for evaluation of translation inhibitors
    Corey Fyfe
    Tetraphase Pharmaceuticals, Inc, Watertown, MA 02472, United States
    J Microbiol Methods 90:256-61. 2012
    ..Results showed a similar ranking of the activities of known inhibitors, illustrative of the high degree of conservation between the transcription-translation pathways in both organisms...
  62. pmc Immune-activating properties of Panton-Valentine leukocidin improve the outcome in a model of methicillin-resistant Staphylococcus aureus pneumonia
    Pauline Yoong
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Infect Immun 80:2894-904. 2012
    ..Our data indicate that, independent of its cytotoxic effects, PVL also plays an important and positive immunomodulatory role during MRSA infections...
  63. pmc A novel small molecule inhibitor of influenza A viruses that targets polymerase function and indirectly induces interferon
    Mila Brum Ortigoza
    Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America
    PLoS Pathog 8:e1002668. 2012
    ..This two-pronged antiviral mechanism, consisting of direct inhibition of virus replication and simultaneous activation of the host innate immune response, is a unique property not previously described for any single antiviral molecule...
  64. pmc A self-produced trigger for biofilm disassembly that targets exopolysaccharide
    Ilana Kolodkin-Gal
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Cell 149:684-92. 2012
    ..Norspermidine, but not closely related polyamines, prevented biofilm formation by B. subtilis, Escherichia coli, and Staphylococcus aureus...
  65. pmc Mutagenesis of the DI/DIII linker in dengue virus envelope protein impairs viral particle assembly
    Melissanne de Wispelaere
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
    J Virol 86:7072-83. 2012
    ..Together, our results suggest a critical and previously unidentified role for the E protein DI/DIII linker region during the DV2 assembly process...
  66. pmc Small-molecule inhibitors of dengue-virus entry
    Aaron G Schmidt
    Jack and Eileen Connors Laboratory of Structural Biology, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Pathog 8:e1002627. 2012
    ..We propose that compounds such as 1662G07 trap the sE trimer in a "pocket-open" state, which has lost affinity for the stem peptide and cannot support the final "zipping up" of the stem...
  67. pmc IFITM proteins restrict antibody-dependent enhancement of dengue virus infection
    Ying Kai Chan
    New England Primate Research Center, Department of Microbiology and Immunobiology, Harvard Medical School, Southborough, Massachusetts, United States of America
    PLoS ONE 7:e34508. 2012
    ..We observed that IFITM proteins restricted ADE-mediated and direct infection with comparable efficiencies in a myelogenous leukemia cell line. Our data suggest that IFITM proteins can contribute to control of secondary DENV infections...
  68. pmc RNA signatures allow rapid identification of pathogens and antibiotic susceptibilities
    Amy K Barczak
    The Broad Institute, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 109:6217-22. 2012
    ..Thus, transcriptional signatures could form the basis of a uniform diagnostic platform applicable across a broad range of infectious agents...
  69. pmc Targeting pan-resistant bacteria with antibodies to a broadly conserved surface polysaccharide expressed during infection
    David Skurnik
    Channing Laboratory, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    J Infect Dis 205:1709-18. 2012
    ....
  70. pmc Cytosolic surveillance and antiviral immunity
    Vijay A K Rathinam
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, MA, USA
    Curr Opin Virol 1:455-62. 2011
    ..Here, we review this expanding area of innate immunity by focusing on the molecular mechanisms of cytosolic host-defenses...
  71. pmc Evidence for ACE2-utilizing coronaviruses (CoVs) related to severe acute respiratory syndrome CoV in bats
    Ann Demogines
    Department of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, USA
    J Virol 86:6350-3. 2012
    ..Our data indicate that ACE2 utilization preceded the emergence of SARS-CoV-like viruses from bats...
  72. pmc Apoptotic cells can deliver chemotherapeutics to engulfing macrophages and suppress inflammatory cytokine production
    BEATRIZ PEREZ
    Program of Developmental Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 287:16029-36. 2012
    ..Furthermore, these effects of cytotoxic drugs on infiltrating immune phagocytes may have clinical ramifications for their use as antitumor therapies...
  73. pmc Regulation of inflammasome signaling
    Vijay A K Rathinam
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Nat Immunol 13:333-42. 2012
    ..Here we discuss the various regulatory mechanisms that have evolved to keep inflammasome signaling in check to maintain immunological balance...
  74. pmc Thiadiazolidinones: a new class of alanine racemase inhibitors with antimicrobial activity against methicillin-resistant Staphylococcus aureus
    Mihai Ciustea
    L2 Diagnostics, LLC, 300 George St, New Haven, CT 06511, USA
    Biochem Pharmacol 83:368-77. 2012
    ..Lead development centering on the thiadiazolidinone series would require additional medicinal chemistry efforts to enhance the antibacterial activity and minimize mammalian cell toxicity...
  75. pmc Forty-five years of Marburg virus research
    Kristina Brauburger
    Department of Microbiology, School of Medicine and National Emerging Infectious Diseases Laboratories Institute, Boston University, Boston, MA 02118, USA
    Viruses 4:1878-927. 2012
    ..This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology...
  76. pmc Single-cell RNA-seq reveals dynamic paracrine control of cellular variation
    Alex K Shalek
    1 Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA 2 Department of Physics, Harvard University, 17 Oxford Street, Cambridge, Massachusetts 02138, USA 3 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA 4
    Nature 510:363-9. 2014
    ..Our study highlights the importance of cell-to-cell communication in controlling cellular heterogeneity and reveals general strategies that multicellular populations can use to establish complex dynamic responses. ..
  77. pmc Uptake of rabies virus into epithelial cells by clathrin-mediated endocytosis depends upon actin
    Silvia Piccinotti
    Department of Microbiology and Immunobiology
    J Virol 87:11637-47. 2013
    ..This work extends to RABV particles the finding that clathrin-mediated endocytosis of rhabdoviruses proceeds through incompletely coated pits which depend upon actin. ..
  78. pmc Clathrin-mediated endocytosis persists during unperturbed mitosis
    Silvia K Tacheva-Grigorova
    Program in Cellular and Molecular Medicine, Boston Children s Hospital, Boston, MA 02115, USA
    Cell Rep 4:659-68. 2013
    ..Thus, our data show that endocytosis is unaffected during all stages of natural cell division. ..
  79. pmc Receptor-directed chimeric toxins created by sortase-mediated protein fusion
    Andrew J McCluskey
    Corresponding Author Andrew J McCluskey, Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115
    Mol Cancer Ther 12:2273-81. 2013
    ..Sortase-mediated ligation of binary combinations of diverse natively folded proteins offers a facile way to produce large sets of chimeric proteins for research and medicine...
  80. pmc Crystal structures of botulinum neurotoxin DC in complex with its protein receptors synaptotagmin I and II
    Ronnie Per Arne Berntsson
    Department of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, Sweden
    Structure 21:1602-11. 2013
    ..The structures suggest that the BoNT/DC ganglioside binding sites are independent of the protein receptor binding site. Our results reveal the remarkable versatility in the receptor recognition of the BoNTs...
  81. pmc Environmental cues dictate the fate of individual CD8+ T cells responding to infection
    Courtney R Plumlee
    Center for Integrated Immunology and Vaccine Research, Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA
    Immunity 39:347-56. 2013
    ....
  82. pmc A high-throughput screen for quorum-sensing inhibitors that target acyl-homoserine lactone synthases
    Quin H Christensen
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 110:13815-20. 2013
    ..Our screen and identification of acyl-HSL synthase inhibitors serve as a basis for efforts to target quorum-sensing signal synthesis as an antivirulence approach. ..
  83. pmc Overexpression of membrane-bound fas ligand (CD95L) exacerbates autoimmune disease and renal pathology in pristane-induced lupus
    Lukas Bossaller
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 191:2104-14. 2013
    ..These results demonstrate that FasL promotes inflammation in TMPD-induced autoimmunity, and its cleavage limits FasL proinflammatory activity. ..
  84. pmc The atypical lipopolysaccharide of Francisella
    Nihal A Okan
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, United States
    Carbohydr Res 378:79-83. 2013
    ..This review discusses both the general characteristics and the unusual features of Francisella LPS...
  85. pmc Detection of proton movement directly across viral membranes to identify novel influenza virus M2 inhibitors
    Chidananda Sulli
    Integral Molecular, Inc, Philadelphia, Pennsylvania, USA
    J Virol 87:10679-86. 2013
    ..In addition to its application to M2 and potentially other ion channels, this technology enables direct measurement of the electrochemical and biophysical characteristics of viral membranes. ..
  86. pmc Structure of dual receptor binding to botulinum neurotoxin B
    Ronnie P A Berntsson
    Department of Biochemistry and Biophysics, Stockholm University, Stockholm 10691, Sweden
    Nat Commun 4:2058. 2013
    ..The structure demonstrates that the protein receptor and the ganglioside receptor occupy nearby but separate binding sites, thus providing two independent anchoring points. ..
  87. pmc Diarylcoumarins inhibit mycolic acid biosynthesis and kill Mycobacterium tuberculosis by targeting FadD32
    Sarah A Stanley
    Infectious Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 110:11565-70. 2013
    ....
  88. pmc Will there ever be a universal Staphylococcus aureus vaccine?
    Gerald B Pier
    Division of Infectious Diseases Department of Medicine Brigham and Women s Hospital Harvard Medical School Boston, MA USA
    Hum Vaccin Immunother 9:1865-76. 2013
    ....
  89. pmc A bacterial export system for generating extracellular amyloid aggregates
    Viknesh Sivanathan
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA
    Nat Protoc 8:1381-90. 2013
    ..Once the appropriate vectors have been constructed, results can be obtained within 1 week...
  90. pmc Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell antigen binding and activation
    Balthasar A Heesters
    the Program in Cellular and Molecular Medicine, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Immunity 38:1164-75. 2013
    ..This would explain how antigens are protected from damage and retained over long periods of time, while remaining accessible for B cells. ..
  91. pmc CCT chaperonin complex is required for efficient delivery of anthrax toxin into the cytosol of host cells
    Louise H Slater
    Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 110:9932-7. 2013
    ..Together, these results suggest that CCT is required for efficient delivery of enzymatically active toxin to the cytosol and are consistent with a direct role for CCT in translocation of LF through the protective antigen pore...
  92. pmc Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens
    Colette Cywes-Bentley
    Division of Infectious Diseases, Department of Medicine, Brigham and Women s Hospital Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 110:E2209-18. 2013
    ..Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology...
  93. pmc Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells
    Alex K Shalek
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
    Nature 498:236-40. 2013
    ..Our study demonstrates the power and promise of single-cell genomics in uncovering functional diversity between cells and in deciphering cell states and circuits...
  94. pmc Live-cell visualization of pre-mRNA splicing with single-molecule sensitivity
    Robert M Martin
    Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649 028 Lisboa, Portugal
    Cell Rep 4:1144-55. 2013
    ..These results have important implications for a mechanistic understanding of cotranscriptional splicing regulation in the live-cell context...
  95. pmc Interferon-induced transmembrane protein 3 is a type II transmembrane protein
    Charles C Bailey
    From the Department of Infectious Diseases, The Scripps Research Institute, Jupiter, Florida 33458 and
    J Biol Chem 288:32184-93. 2013
    ..Collectively, our results demonstrate a type II transmembrane topology for Ifitm3 and will provide insight into its interaction with potential targets and cofactors. ..
  96. pmc Crystal structures of ricin toxin's enzymatic subunit (RTA) in complex with neutralizing and non-neutralizing single-chain antibodies
    Michael J Rudolph
    New York Structural Biology Center, New York, NY 10027, USA Electronic address
    J Mol Biol 426:3057-68. 2014
    ..These structures provide unique insights into the mechanisms underlying toxin neutralization and provide critically important information required for the rational design of ricin toxin subunit vaccines. ..
  97. pmc Evaluation of impermeant, DNA-binding dye fluorescence as a real-time readout of eukaryotic cell toxicity in a high throughput screening format
    Lucius Chiaraviglio
    Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
    Assay Drug Dev Technol 12:219-28. 2014
    ....
  98. pmc Key interactions for clathrin coat stability
    Till Böcking
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA Centre for Vascular Research, University of New South Wales, Sydney NSW 2052 Australia Electronic address
    Structure 22:819-29. 2014
    ..Coats destabilized by these mutations require fewer Hsc70 molecules to initiate disassembly, as predicted by a model in which Hsc70 traps conformational distortions during the auxilin- and Hsc70:ATP-mediated uncoating reaction. ..
  99. ncbi Small molecule inhibitor discovery for dengue virus protease using high-throughput screening
    Mark Manzano
    Department of Microbiology Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
    Methods Mol Biol 1138:331-44. 2014
    ..In this chapter, we describe an in vitro assay for the viral serine protease that has been successfully adapted to HTS format and has been used to screen several thousand compounds to identify inhibitors of the viral protease...

Research Grants30

  1. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..