Sanjay Ram

Summary

Affiliation: University of Massachusetts Medical School
Country: USA

Publications

  1. pmc Meningococcal group W-135 and Y capsular polysaccharides paradoxically enhance activation of the alternative pathway of complement
    Sanjay Ram
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 286:8297-307. 2011
  2. pmc Heptose I glycan substitutions on Neisseria gonorrhoeae lipooligosaccharide influence C4b-binding protein binding and serum resistance
    Sanjay Ram
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Lazare Research Building, Room 322, 364 Plantation Street, Worcester, MA 01605, USA
    Infect Immun 75:4071-81. 2007
  3. pmc Infections of people with complement deficiencies and patients who have undergone splenectomy
    Sanjay Ram
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Lazare Research Building, Room 322, 364 Plantation Street, Worcester, MA 01605, USA
    Clin Microbiol Rev 23:740-80. 2010
  4. pmc Molecular characterization of the interaction between sialylated Neisseria gonorrhoeae and factor H
    Jutamas Shaughnessy
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 286:22235-42. 2011
  5. pmc Immunization against a saccharide epitope accelerates clearance of experimental gonococcal infection
    Sunita Gulati
    Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS Pathog 9:e1003559. 2013
  6. pmc Phosphoethanolamine residues on the lipid A moiety of Neisseria gonorrhoeae lipooligosaccharide modulate binding of complement inhibitors and resistance to complement killing
    Lisa A Lewis
    Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts School of Medicine, Worcester, Massachusetts, USA
    Infect Immun 81:33-42. 2013
  7. ncbi request reprint Human factor H interacts selectively with Neisseria gonorrhoeae and results in species-specific complement evasion
    Jutamas Ngampasutadol
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 180:3426-35. 2008
  8. pmc ArcA-regulated glycosyltransferase lic2B promotes complement evasion and pathogenesis of nontypeable Haemophilus influenzae
    Sandy M S Wong
    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 55 Lake Ave N, S6 242, Worcester, MA 01655, USA
    Infect Immun 79:1971-83. 2011
  9. pmc Defining targets for complement components C4b and C3b on the pathogenic neisseriae
    Lisa A Lewis
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Lazare Research Building, Room 370I, 364 Plantation Street, Worcester, MA 01605, USA
    Infect Immun 76:339-50. 2008
  10. pmc Factor H-dependent alternative pathway inhibition mediated by porin B contributes to virulence of Neisseria meningitidis
    Lisa A Lewis
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    MBio 4:e00339-13. 2013

Research Grants

Collaborators

Detail Information

Publications41

  1. pmc Meningococcal group W-135 and Y capsular polysaccharides paradoxically enhance activation of the alternative pathway of complement
    Sanjay Ram
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 286:8297-307. 2011
    ..These data highlight the heterogeneity of AP activation on the various meningococcal serogroups that may contribute to differences in their pathogenic mechanisms...
  2. pmc Heptose I glycan substitutions on Neisseria gonorrhoeae lipooligosaccharide influence C4b-binding protein binding and serum resistance
    Sanjay Ram
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Lazare Research Building, Room 322, 364 Plantation Street, Worcester, MA 01605, USA
    Infect Immun 75:4071-81. 2007
    ..This study provides mechanistic insights into how HepI LOS substitutions affect the serum resistance of N. gonorrhoeae...
  3. pmc Infections of people with complement deficiencies and patients who have undergone splenectomy
    Sanjay Ram
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Lazare Research Building, Room 322, 364 Plantation Street, Worcester, MA 01605, USA
    Clin Microbiol Rev 23:740-80. 2010
    ..Paramount to the management of patients with complement deficiencies and asplenia is educating patients about their predisposition to infection and the importance of preventive immunizations and seeking prompt medical attention...
  4. pmc Molecular characterization of the interaction between sialylated Neisseria gonorrhoeae and factor H
    Jutamas Shaughnessy
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 286:22235-42. 2011
    ..These findings provide further insights into the species specificity of gonococcal infections and proof-of-concept of a novel therapeutic approach against gonorrhea, a disease rapidly becoming resistant to conventional antibiotics...
  5. pmc Immunization against a saccharide epitope accelerates clearance of experimental gonococcal infection
    Sunita Gulati
    Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS Pathog 9:e1003559. 2013
    ..043). The OS epitope defined by mAb 2C7 may represent an effective vaccine target against gonorrhea, which is rapidly becoming incurable with currently available antibiotics. ..
  6. pmc Phosphoethanolamine residues on the lipid A moiety of Neisseria gonorrhoeae lipooligosaccharide modulate binding of complement inhibitors and resistance to complement killing
    Lisa A Lewis
    Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts School of Medicine, Worcester, Massachusetts, USA
    Infect Immun 81:33-42. 2013
    ..These data indicate that replacement of lipid A with PEA alters binding of C4BP and fH to PorB and contributes to the ability of gonococci to resist complement-mediated killing...
  7. ncbi request reprint Human factor H interacts selectively with Neisseria gonorrhoeae and results in species-specific complement evasion
    Jutamas Ngampasutadol
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 180:3426-35. 2008
    ..Our findings may help to improve animal models for gonorrhea while also having implications in the choice of complement sources to evaluate neisserial vaccine candidates...
  8. pmc ArcA-regulated glycosyltransferase lic2B promotes complement evasion and pathogenesis of nontypeable Haemophilus influenzae
    Sandy M S Wong
    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 55 Lake Ave N, S6 242, Worcester, MA 01655, USA
    Infect Immun 79:1971-83. 2011
    ....
  9. pmc Defining targets for complement components C4b and C3b on the pathogenic neisseriae
    Lisa A Lewis
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Lazare Research Building, Room 370I, 364 Plantation Street, Worcester, MA 01605, USA
    Infect Immun 76:339-50. 2008
    ..The binding of C3b and C4b to Opa provides a rationale for the recovery of predominantly "transparent" (Opa-negative) neisserial isolates from persons with invasive disease, where the bacteria encounter high levels of complement...
  10. pmc Factor H-dependent alternative pathway inhibition mediated by porin B contributes to virulence of Neisseria meningitidis
    Lisa A Lewis
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    MBio 4:e00339-13. 2013
    ..These results associate PorB2 expression with serum resistance and presage the appearance of fHbp-null and hypervirulent ST-11 isolates that may evade killing by fHbp-based vaccines...
  11. pmc Properdin is critical for antibody-dependent bactericidal activity against Neisseria gonorrhoeae that recruit C4b-binding protein
    Sunita Gulati
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 188:3416-25. 2012
    ..Collectively, these data point to an important role for properdin in facilitating immune Ab-mediated complement-dependent killing of gonococcal strains that inhibit the classical pathway by recruiting C4BP...
  12. ncbi request reprint Species-specificity of Neisseria gonorrhoeae infection: do human complement regulators contribute?
    Jutamas Ngampasutadol
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States
    Vaccine 26:I62-6. 2008
    ..Our findings may help to improve animal models for gonorrhea while also having implications in the choice of complement sources to evaluate neisserial vaccine candidates...
  13. pmc The meningococcal vaccine candidate neisserial surface protein A (NspA) binds to factor H and enhances meningococcal resistance to complement
    Lisa A Lewis
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    PLoS Pathog 6:e1001027. 2010
    ..Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components...
  14. pmc Novel blocking human IgG directed against the pentapeptide repeat motifs of Neisseria meningitidis Lip/H.8 and Laz lipoproteins
    Tathagat Dutta Ray
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 186:4881-94. 2011
    ..We also propose that outer membrane vesicle-containing meningococcal vaccines may be more efficacious if purged of subversive immunogens such as H.8...
  15. doi request reprint Outer membrane protein P5 is required for resistance of nontypeable Haemophilus influenzae to both the classical and alternative complement pathways
    Charles V Rosadini
    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Infect Immun 82:640-9. 2014
    ..Collectively, the results obtained in this work highlight the ability of H. influenzae to utilize a single protein to perform multiple protective functions for evading host immunity. ..
  16. pmc The relative roles of factor H binding protein, neisserial surface protein A, and lipooligosaccharide sialylation in regulation of the alternative pathway of complement on meningococci
    Lisa A Lewis
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 188:5063-72. 2012
    ..These data highlight the cooperative roles of meningococcal NspA and fHbp in regulating the human AP and broaden the molecular basis for LOS sialylation in AP regulation on meningococci in more than one animal species...
  17. pmc Factor H facilitates adherence of Neisseria gonorrhoeae to complement receptor 3 on eukaryotic cells
    Sarika Agarwal
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 185:4344-53. 2010
    ..These results indicate adherence between fH-coated gonococci and CR3 and may provide a means for gonococci to gain sanctuary into nonprofessional phagocytes...
  18. pmc Functional comparison of the binding of factor H short consensus repeat 6 (SCR 6) to factor H binding protein from Neisseria meningitidis and the binding of factor H SCR 18 to 20 to Neisseria gonorrhoeae porin
    Jutamas Shaughnessy
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Lazare Research Building, Room 370I, Plantation Street, Worcester, MA 01605, USA
    Infect Immun 77:2094-103. 2009
    ..Differences in fH binding to these two related pathogens may be important for modulating their individual responses to host immune attack...
  19. pmc Enhanced factor H binding to sialylated Gonococci is restricted to the sialylated lacto-N-neotetraose lipooligosaccharide species: implications for serum resistance and evidence for a bifunctional lipooligosaccharide sialyltransferase in Gonococci
    Sunita Gulati
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Infect Immun 73:7390-7. 2005
    ..Thus, serum resistance mediated by sialylation of gonococcal L1 and LNT LOS occurs by different mechanisms, and specificity of factor H binding to sialylated gonococci is restricted to the LNT LOS species...
  20. pmc Phosphoethanolamine substitution of lipid A and resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides and complement-mediated killing by normal human serum
    Lisa A Lewis
    Department of Medicine, University of Massachusetts School of Medicine, Worcester, Massachusetts, USA
    Infect Immun 77:1112-20. 2009
    ..Our results support a role for lipid A phosphoethanolamine substitutions in resistance of this strict human pathogen to innate host defenses...
  21. pmc An evaluation of the role of properdin in alternative pathway activation on Neisseria meningitidis and Neisseria gonorrhoeae
    Sarika Agarwal
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 185:507-16. 2010
    ..meningitidis or N. gonorrhoeae but play a crucial role in augmenting AP-dependent C3 deposition on the bacteria through the "conventional" mechanism of stabilizing AP C3 convertases...
  22. pmc Relative contributions of dectin-1 and complement to immune responses to particulate β-glucans
    Haibin Huang
    Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 189:312-7. 2012
    ..In addition, Th-skewing after GP-based immunization was altered in C3(-/-) mice...
  23. doi request reprint Outer Membrane Protein P5 Is Required for Resistance of Nontypeable Haemophilus influenzae to Both the Classical and Alternative Complement Pathways
    Charles V Rosadini
    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Infect Immun 82:640-9. 2014
    ..Collectively, the results obtained in this work highlight the ability of H. influenzae to utilize a single protein to perform multiple protective functions for evading host immunity. ..
  24. pmc The ArcA regulon and oxidative stress resistance in Haemophilus influenzae
    Sandy M S Wong
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Mol Microbiol 64:1375-90. 2007
    ..influenzae arcA and dps in pre-emptive defence against transitions from growth in low oxygen environments to aerobic exposure to hydrogen peroxide, an antibacterial oxidant produced by phagocytes during infection...
  25. pmc Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection
    Jutamas Ngampasutadol
    Section of Infectious Diseases, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USA
    Proc Natl Acad Sci U S A 102:17142-7. 2005
    ..Our findings may lead to the development of better animal models for gonorrhea and may also have implications in the choice of complement sources to evaluate neisserial vaccine candidates...
  26. ncbi request reprint Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis
    Hanna Jarva
    Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland
    J Immunol 174:6299-307. 2005
    ..PorA-expressing strains were also more resistant to C lysis than PorA-negative strains in a serum bactericidal assay. Binding of C4bp thus helps Neisseria meningitidis to escape CP complement activation...
  27. ncbi request reprint Neisserial lipooligosaccharide is a target for complement component C4b. Inner core phosphoethanolamine residues define C4b linkage specificity
    Sanjay Ram
    Section of Infectious Diseases, Evans Biomedical Research Center, Boston University Medical Center, Boston, Massachusetts 02118, USA
    J Biol Chem 278:50853-62. 2003
    ....
  28. pmc Killing of dsrA mutants of Haemophilus ducreyi by normal human serum occurs via the classical complement pathway and is initiated by immunoglobulin M binding
    Malikah Abdullah
    Department of Medicine, Campus Box 7031, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Infect Immun 73:3431-9. 2005
    ..We speculate that an undefined neo-epitope, possibly carbohydrate, is exposed in the dsrA mutant that is recognized by naturally occurring bactericidal IgM antibodies present in human sera...
  29. ncbi request reprint The role of porins in neisserial pathogenesis and immunity
    Paola Massari
    Department of Medicine, Division of Infectious Diseases, Boston University School of Medicine, Boston, MA 02118, USA
    Trends Microbiol 11:87-93. 2003
    ..Furthermore, neisserial porins co-localize with mitochondria of target cells, where they appear to modulate apoptosis...
  30. ncbi request reprint Regulation of the mannan-binding lectin pathway of complement on Neisseria gonorrhoeae by C1-inhibitor and alpha 2-macroglobulin
    Sunita Gulati
    Section of Infectious Diseases and Hematology Oncology, Evans Biomedical Research Center, Boston University Medical Center, Boston, MA 02118, USA
    J Immunol 168:4078-86. 2002
    ..Our studies indicate that MBL does not participate in complement activation on N. gonorrhoeae in the presence of "complete" serum that contains C1-inhibitor and alpha(2)-macroglobulin...
  31. pmc Phenotypic and genotypic analyses of Neisseria gonorrhoeae isolates that express frequently recovered PorB PIA variable region types suggest that certain P1a porin sequences confer a selective advantage for urogenital tract infection
    Lotisha E Garvin
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20853 4799, USA
    Infect Immun 76:3700-9. 2008
    ..The capacity of some porin types to evade a porin-specific adaptive immune response must also be considered...
  32. pmc The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance
    Guillermo Madico
    Section of Infectious Diseases, Boston University School of Medicine, Boston, MA 02118, USA
    J Immunol 177:501-10. 2006
    ..These data provide further support for inclusion of this molecule in a meningococcal vaccine. To reflect the critical function of this molecule, we suggest calling it fH-binding protein...
  33. ncbi request reprint Molecular characterization of the interaction between porins of Neisseria gonorrhoeae and C4b-binding protein
    Hanna Jarva
    Department of Laboratory Medicine, Division of Medical Protein Chemistry, University of Lund, Malmo, Sweden
    J Immunol 179:540-7. 2007
    ..Only those recombinant mutant C4BPs that bound to bacteria rescued them from 100% killing by rhesus serum, thereby providing a functional correlate for the binding studies and highlighting C4BP function in gonococcal serum resistance...
  34. ncbi request reprint lgtC expression modulates resistance to C4b deposition on an invasive nontypeable Haemophilus influenzae
    Derek K Ho
    Department of Pathobiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA
    J Immunol 178:1002-12. 2007
    ..Alteration of surface glycans of NTHi may be a critical event in determining the ability of a strain to evade host defenses and cause disseminated infection...
  35. ncbi request reprint Factor H binding and function in sialylated pathogenic neisseriae is influenced by gonococcal, but not meningococcal, porin
    Guillermo Madico
    Evans Biomedical Research Center, Boston University Medical Center, Boston, MA 02118, USA
    J Immunol 178:4489-97. 2007
    ..Our data highlight the different mechanisms used by these two related species to evade complement...
  36. doi request reprint Complement-dependent synergistic bactericidal activity of antibodies against factor H-binding protein, a sparsely distributed meningococcal vaccine antigen
    Jo Anne Welsch
    Center for Immunobiology and Vaccine Development, Children s Hospital Oakland Research Institute, Oakland, California, USA
    J Infect Dis 197:1053-61. 2008
    ..Antibodies to factor H (fH)-binding protein (fHBP), a meningococcal vaccine antigen, activate classical complement pathway serum bactericidal activity (SBA) and block binding of the complement inhibitor fH...
  37. pmc Multiple consecutive lavage samplings reveal greater burden of disease and provide direct access to the nontypeable Haemophilus influenzae biofilm in experimental otitis media
    Magali Leroy
    Section of Molecular Genetics, Division of Pediatric Infectious Diseases, The Maxwell Finland Laboratory for Infectious Diseases, Boston University School of Medicine, Boston Medical Center, 774 Albany Street, Boston, MA 02118, USA
    Infect Immun 75:4158-72. 2007
    ..Such findings may have direct implications for antibiotic treatment and vaccine development against NTHi...
  38. ncbi request reprint The Lip lipoprotein from Neisseria gonorrhoeae stimulates cytokine release and NF-kappaB activation in epithelial cells in a Toll-like receptor 2-dependent manner
    Philip L Fisette
    Division of Infectious Diseases, Department of Physiology and Biophysics, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA
    J Biol Chem 278:46252-60. 2003
    ..8/Lip in HEK cells was enhanced upon coexpression of TLR1 but not TLR6. These observations provide evidence that Lip is capable of inducing the release of inflammatory mediators from epithelial cells in a TLR2-dependent manner...
  39. ncbi request reprint Interactions between Neisseria meningitidis and the complement system
    Muriel C Schneider
    Centre for Molecular Microbiology and Infection, Department of Infectious Diseases, Flowers Building, Armstrong Road, Imperial College London, London, SW7 2AZ, UK
    Trends Microbiol 15:233-40. 2007
    ..meningitidis avoids complement-mediated killing, and how polymorphisms in genes encoding human complement proteins affect susceptibility to this important human pathogen...
  40. pmc Role of complement in defense of the middle ear revealed by restoring the virulence of nontypeable Haemophilus influenzae siaB mutants
    Marisol A Figueira
    Section of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Room 508, 774 Albany Street, Boston Medical Center, Boston, MA 02118, USA
    Infect Immun 75:325-33. 2007
    ..influenzae strains, which in turn may impact their virulence. These data demonstrate a central role for complement in innate immune defenses against NT H. influenzae infections and specifically EOM...
  41. pmc Binding of vitronectin by the Moraxella catarrhalis UspA2 protein interferes with late stages of the complement cascade
    Ahmed S Attia
    Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9048, USA
    Infect Immun 74:1597-611. 2006
    ..These results indicate that binding of vitronectin by UspA2 is involved in the serum resistance of M. catarrhalis; this represents the first example of vitronectin-mediated serum resistance on a microbe...

Research Grants7

  1. Complement Activation on Neisseria meningitidis
    Sanjay Ram; Fiscal Year: 2007
    ....
  2. Complement Activation on Neisseria meningitidis
    Sanjay Ram; Fiscal Year: 2010
    ..The studies proposed in this application will help us better understand how this pathogen escapes killing by complement and will ultimately aid in the development of better vaccines against meningococcal meningitis. ..