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The focus of our group is to elucidate how the complement system (an arm of innate immune defenses) interacts with Neisseria gonorrhoeae (the bacteria that cause gonorrhea) and N. meningitidis (the agent of bacterial meningitis).  This knowledge is now being used to develop novel immunotherapeutics and vaccines against multidrug-resistant gonorrhea.  Gonococci scavenge host complement inhibitors to escape killing by complement.  The first approach being investigated includes fusing the microbial binding region of complement inhibitors with the Fc region of antibody, which enhances complement-dependent lysis of bacteria.  A key aspect of gonococcal pathogenesis is its ability to use a sugar called sialic acid from the host to escape immune defenses.  In the second approach, we are investigating the use of analogs of sialic acid that are taken up by the bacteria, but unlike the ‘physiological’ form of sialic acid, fail to protect the bacteria against host defenses and results in faster clearance of bacteria in the murine model of gonorrhea. In collaboration with Dr. Peter Rice's group at UMass, our group is developing a monoclonal antibody and a vaccine that target a gonococcal glycan epitope. 


 

One or more keywords matched the following items that are connected to Ram, Sanjay
Item TypeName
Academic Article The role of porins in neisserial pathogenesis and immunity.
Academic Article Binding of vitronectin by the Moraxella catarrhalis UspA2 protein interferes with late stages of the complement cascade.
Academic Article The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance.
Academic Article Role of complement in defense of the middle ear revealed by restoring the virulence of nontypeable Haemophilus influenzae siaB mutants.
Academic Article lgtC expression modulates resistance to C4b deposition on an invasive nontypeable Haemophilus influenzae.
Academic Article Factor H binding and function in sialylated pathogenic neisseriae is influenced by gonococcal, but not meningococcal, porin.
Academic Article Molecular characterization of the interaction between porins of Neisseria gonorrhoeae and C4b-binding protein.
Academic Article Complement-dependent synergistic bactericidal activity of antibodies against factor H-binding protein, a sparsely distributed meningococcal vaccine antigen.
Academic Article Binding of complement factor H (fH) to Neisseria meningitidis is specific for human fH and inhibits complement activation by rat and rabbit sera.
Academic Article Role of complement in host defense against pneumococcal otitis media.
Academic Article Factor H and neisserial pathogenesis.
Academic Article Impaired immunogenicity of a meningococcal factor H-binding protein vaccine engineered to eliminate factor h binding.
Academic Article Infections of people with complement deficiencies and patients who have undergone splenectomy.
Academic Article Meningococcal group W-135 and Y capsular polysaccharides paradoxically enhance activation of the alternative pathway of complement.
Academic Article A meningococcal factor H binding protein mutant that eliminates factor H binding enhances protective antibody responses to vaccination.
Academic Article Regulation of the mannan-binding lectin pathway of complement on Neisseria gonorrhoeae by C1-inhibitor and alpha 2-macroglobulin.
Academic Article Linkage specificity and role of properdin in activation of the alternative complement pathway by fungal glycans.
Academic Article Enhanced bacteremia in human factor H transgenic rats infected by Neisseria meningitidis.
Academic Article Properdin is critical for antibody-dependent bactericidal activity against Neisseria gonorrhoeae that recruit C4b-binding protein.
Academic Article 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.
Academic Article The effect of human factor H on immunogenicity of meningococcal native outer membrane vesicle vaccines with over-expressed factor H binding protein.
Academic Article Phosphoethanolamine residues on the lipid A moiety of Neisseria gonorrhoeae lipooligosaccharide modulate binding of complement inhibitors and resistance to complement killing.
Academic Article Neisserial lipooligosaccharide is a target for complement component C4b. Inner core phosphoethanolamine residues define C4b linkage specificity.
Academic Article Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis.
Academic Article Killing of dsrA mutants of Haemophilus ducreyi by normal human serum occurs via the classical complement pathway and is initiated by immunoglobulin M binding.
Academic Article 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.
Academic Article Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection.
Academic Article Interactions between Neisseria meningitidis and the complement system.
Academic Article Heptose I glycan substitutions on Neisseria gonorrhoeae lipooligosaccharide influence C4b-binding protein binding and serum resistance.
Academic Article Defining targets for complement components C4b and C3b on the pathogenic neisseriae.
Academic Article Human factor H interacts selectively with Neisseria gonorrhoeae and results in species-specific complement evasion.
Academic Article 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.
Academic Article Phosphoethanolamine substitution of lipid A and resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides and complement-mediated killing by normal human serum.
Academic Article 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.
Academic Article Contribution of interactions between complement inhibitor C4b-binding protein and pathogens to their ability to establish infection with particular emphasis on Neisseria gonorrhoeae.
Academic Article Species-specificity of Neisseria gonorrhoeae infection: do human complement regulators contribute?
Academic Article An evaluation of the role of properdin in alternative pathway activation on Neisseria meningitidis and Neisseria gonorrhoeae.
Academic Article The meningococcal vaccine candidate neisserial surface protein A (NspA) binds to factor H and enhances meningococcal resistance to complement.
Academic Article Factor H facilitates adherence of Neisseria gonorrhoeae to complement receptor 3 on eukaryotic cells.
Academic Article ArcA-regulated glycosyltransferase lic2B promotes complement evasion and pathogenesis of nontypeable Haemophilus influenzae.
Academic Article Molecular characterization of the interaction between sialylated Neisseria gonorrhoeae and factor H.
Academic Article Relative contributions of dectin-1 and complement to immune responses to particulate ?-glucans.
Academic Article Does binding of complement factor H to the meningococcal vaccine antigen, factor H binding protein, decrease protective serum antibody responses?
Concept Complement C1 Inactivator Proteins
Concept Complement C3b Inactivator Proteins
Concept Complement C4b-Binding Protein
Concept Complement C3-C5 Convertases, Alternative Pathway
Concept Complement Factor I
Concept Complement Pathway, Classical
Concept Complement C3a
Concept Complement Factor H
Concept Complement Inactivator Proteins
Concept Complement System Proteins
Concept Receptors, Complement
Concept Complement C3d
Concept Complement Inactivating Agents
Concept Complement C4
Concept Complement C3 Convertase, Alternative Pathway
Concept Receptors, Complement 3b
Concept Complement C1
Concept Complement C3b
Concept Complement Activation
Concept Complement Pathway, Alternative
Concept Complement C1q
Concept Complement C4b
Concept Complement C5
Concept Complement C3
Academic Article Increased survival in B-cell-deficient mice during experimental cerebral malaria suggests a role for circulating immune complexes.
Academic Article Development of a large scale human complement source for use in bacterial immunoassays.
Academic Article Meningococcal disease and the complement system.
Academic Article Factor H-dependent alternative pathway inhibition mediated by porin B contributes to virulence of Neisseria meningitidis.
Academic Article Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum.
Academic Article Outer membrane protein P5 is required for resistance of nontypeable Haemophilus influenzae to both the classical and alternative complement pathways.
Academic Article Inhibition of the alternative pathway of nonhuman infant complement by porin B2 contributes to virulence of Neisseria meningitidis in the infant rat model.
Academic Article Inhibition of the classical pathway of complement by meningococcal capsular polysaccharides.
Academic Article Fusion protein comprising factor H domains 6 and 7 and human IgG1 Fc as an antibacterial immunotherapeutic.
Academic Article Heterogeneity in rhesus macaque complement factor H binding to meningococcal factor H binding protein (FHbp) informs selection of primates to assess immunogenicity of FHbp-based vaccines.
Academic Article a-2,3-sialyltransferase expression level impacts the kinetics of lipooligosaccharide sialylation, complement resistance, and the ability of Neisseria gonorrhoeae to colonize the murine genital tract.
Academic Article Binding of complement factor H to PorB3 and NspA enhances resistance of Neisseria meningitidis to anti-factor H binding protein bactericidal activity.
Academic Article Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors.
Academic Article Utilizing CMP-Sialic Acid Analogs to Unravel Neisseria gonorrhoeae Lipooligosaccharide-Mediated Complement Resistance and Design Novel Therapeutics.
Academic Article A Novel Factor H-Fc Chimeric Immunotherapeutic Molecule against Neisseria gonorrhoeae.
Academic Article Defining the Binding Region in Factor H to Develop a Therapeutic Factor H-Fc Fusion Protein against Non-Typeable Haemophilus influenzae.
Academic Article Utilizing complement evasion strategies to design complement-based antibacterial immunotherapeutics: Lessons from the pathogenic Neisseriae.
Academic Article Gonococcal lipooligosaccharide sialylation: virulence factor and target for novel immunotherapeutics.
Academic Article Human IgG Increases Virulence of Streptococcus pyogenes through Complement Evasion.
Academic Article Human Factor H Domains 6 and 7 Fused to IgG1 Fc Are Immunotherapeutic against Neisseria gonorrhoeae.
Academic Article Polymorphic factor H-binding activity of CspA protects Lyme borreliae from the host complement in feeding ticks to facilitate tick-to-host transmission.
Academic Article Factor H-IgG Chimeric Proteins as a Therapeutic Approach against the Gram-Positive Bacterial Pathogen Streptococcus pyogenes.
Academic Article No Good Deed Goes Unpunished: Eculizumab and Invasive Neisserial Infections.
Academic Article Species-specific differences in regulation of macrophage inflammation by the C3a-C3a receptor axis.
Academic Article Bacterial complement escape.
Academic Article Role of Gonococcal Neisserial Surface Protein A (NspA) in Serum Resistance and Comparison of Its Factor H Binding Properties with Those of Its Meningococcal Counterpart.
Academic Article Mature neutrophils suppress T cell immunity in ovarian cancer microenvironment.
Academic Article Targeting Lipooligosaccharide (LOS) for a Gonococcal Vaccine.
Academic Article Complement-Dependent Serum Bactericidal Assays for Neisseria gonorrhoeae.
Academic Article The Molecular Basis of Human IgG-Mediated Enhancement of C4b-Binding Protein Recruitment to Group A Streptococcus.
Academic Article Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody.
Academic Article Blood treatment of Lyme borreliae demonstrates the mechanism of CspZ-mediated complement evasion to promote systemic infection in vertebrate hosts.
Academic Article The hijackers guide to escaping complement: Lessons learned from pathogens.
Academic Article C4BP-IgM protein as a therapeutic approach to treat Neisseria gonorrhoeae infections.
Academic Article Effect of a C1s Inhibitor on the Efficacy of Anti-Capsular Antibodies against Neisseria meningitidis and Streptococcus pneumoniae.
Academic Article A soft tick Ornithodoros moubata salivary protein OmCI is a potent inhibitor to prevent avian complement activation.
Academic Article Complement interactions with the pathogenic Neisseriae: clinical features, deficiency states, and evasion mechanisms.
Academic Article Therapeutic CMP-Nonulosonates against Multidrug-Resistant Neisseria gonorrhoeae.
Academic Article Efficacy of Antigonococcal CMP-Nonulosonate Therapeutics Require Cathelicidins.
Academic Article Antibacterial Fusion Proteins Enhance Moraxella catarrhalis Killing.
Academic Article Development of Complement Factor H-Based Immunotherapeutic Molecules in Tobacco Plants Against Multidrug-Resistant Neisseria gonorrhoeae.
Academic Article Exploring the Impact of Ketodeoxynonulosonic Acid in Host-Pathogen Interactions Using Uptake and Surface Display by Nontypeable Haemophilus influenzae.
Academic Article Synthetic DNA Delivery of an Optimized and Engineered Monoclonal Antibody Provides Rapid and Prolonged Protection against Experimental Gonococcal Infection.
Academic Article Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system.
Academic Article Serum Complement Activation by C4BP-IgM Fusion Protein Can Restore Susceptibility to Antibiotics in Neisseria gonorrhoeae.
Academic Article Efficacy of an Experimental Gonococcal Lipooligosaccharide Mimitope Vaccine Requires Terminal Complement.
Academic Article Alternative pathway amplification and infections.
Academic Article An optimized Factor H-Fc fusion protein against multidrug-resistant Neisseria gonorrhoeae.
Academic Article Gardnerella Vaginolysin Potentiates Glycan Molecular Mimicry by Neisseria gonorrhoeae.
Academic Article Low-frequency inherited complement receptor variants are associated with purpura fulminans.
Academic Article Mechanisms by which Factor H protects Trypanosoma cruzi from the alternative pathway of complement.
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  • Complement C6