S J Projan

Summary

Affiliation: Wyeth Research
Country: USA

Publications

  1. ncbi Why is big Pharma getting out of antibacterial drug discovery?
    Steven J Projan
    Wyeth Research, Pearl River NY 10965, USA
    Curr Opin Microbiol 6:427-30. 2003
  2. ncbi Small molecules for small minds? The case for biologic pharmaceuticals
    Steven J Projan
    Department of Protein Technologies, Wyeth Research, Cambridge, MA 02140, USA
    Expert Opin Biol Ther 4:1345-50. 2004
  3. ncbi Staphylococcal vaccines and immunotherapy: to dream the impossible dream?
    Steven J Projan
    Wyeth Research, 87 CambridgePark Drive, Cambridge MA 02140, USA
    Curr Opin Pharmacol 6:473-9. 2006
  4. ncbi Late stage antibacterial drugs in the clinical pipeline
    Steven J Projan
    Wyeth Research, 87 CambridgePark Drive, Cambridge, MA 02140, USA
    Curr Opin Microbiol 10:441-6. 2007
  5. pmc Increased retention of functional fusions to toxic genes in new two-hybrid libraries of the E. coli strain MG1655 and B. subtilis strain 168 genomes, prepared without passaging through E. coli
    Steven A Haney
    Department of Infectious Disease, Wyeth Research, 401 N, Middletown Rd, Pearl River, NY 10965, USA
    BMC Genomics 4:36. 2003
  6. ncbi New (and not so new) antibacterial targets - from where and when will the novel drugs come?
    Steven J Projan
    Wyeth Research, Pearl River, NY 10965, USA
    Curr Opin Pharmacol 2:513-22. 2002
  7. ncbi Antibacterial drug discovery: is it all downhill from here?
    S J Projan
    Wyeth Research, Cambridge, MA 02140, USA
    Clin Microbiol Infect 10:18-22. 2004
  8. pmc (Genome) size matters
    Steven J Projan
    Department of Biological Technologies, Wyeth Research, Biological Technologies, 87 Cambridge Park Dr, Cambridge, MA 02140, USA
    Antimicrob Agents Chemother 51:1133-4. 2007
  9. pmc Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC beta-lactamase, and the foss of an outer membrane protein
    P A Bradford
    Wyeth Ayerst Research, Pearl River, New York 10965, USA
    Antimicrob Agents Chemother 41:563-9. 1997
  10. pmc Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci
    P M Dunman
    Infectious Diseases, Wyeth Ayerst Research, Pearl River, New York 10965, USA
    J Bacteriol 183:7341-53. 2001

Collaborators

Detail Information

Publications38

  1. ncbi Why is big Pharma getting out of antibacterial drug discovery?
    Steven J Projan
    Wyeth Research, Pearl River NY 10965, USA
    Curr Opin Microbiol 6:427-30. 2003
    ..Coupled with the failure of large investments into target-based approaches to produce novel antibacterial agents, companies large and small have exited from this field despite a growing clinical need...
  2. ncbi Small molecules for small minds? The case for biologic pharmaceuticals
    Steven J Projan
    Department of Protein Technologies, Wyeth Research, Cambridge, MA 02140, USA
    Expert Opin Biol Ther 4:1345-50. 2004
    ..g., in oncology). As each aspect of protein pharmaceutical technology advances, it is clear that this will be the major area for growth in the industry over the next decade...
  3. ncbi Staphylococcal vaccines and immunotherapy: to dream the impossible dream?
    Steven J Projan
    Wyeth Research, 87 CambridgePark Drive, Cambridge MA 02140, USA
    Curr Opin Pharmacol 6:473-9. 2006
    ..In this case, Staphylococcus aureus possesses "weapons of mass destruction" and appears to be using them effectively as part of anti-immunization insurgency...
  4. ncbi Late stage antibacterial drugs in the clinical pipeline
    Steven J Projan
    Wyeth Research, 87 CambridgePark Drive, Cambridge, MA 02140, USA
    Curr Opin Microbiol 10:441-6. 2007
    ..Whereas many of these may successfully deal with resistant strains of Gram-positive pathogens, there is very little in development to address the gorwing unmet medical need of multi-drug resistant Gram-negative infections...
  5. pmc Increased retention of functional fusions to toxic genes in new two-hybrid libraries of the E. coli strain MG1655 and B. subtilis strain 168 genomes, prepared without passaging through E. coli
    Steven A Haney
    Department of Infectious Disease, Wyeth Research, 401 N, Middletown Rd, Pearl River, NY 10965, USA
    BMC Genomics 4:36. 2003
    ..coli or yeast gene products in these systems has been shown to be growth inhibitory, and therefore these clones are underrepresented (or completely lost) in the amplified library...
  6. ncbi New (and not so new) antibacterial targets - from where and when will the novel drugs come?
    Steven J Projan
    Wyeth Research, Pearl River, NY 10965, USA
    Curr Opin Pharmacol 2:513-22. 2002
    ..Targeting multidrug efflux pumps may be more edifying in the long run...
  7. ncbi Antibacterial drug discovery: is it all downhill from here?
    S J Projan
    Wyeth Research, Cambridge, MA 02140, USA
    Clin Microbiol Infect 10:18-22. 2004
    ..Therefore, a clear and urgent need for finding ways to improve the level and quality of industrial research in this area is apparent...
  8. pmc (Genome) size matters
    Steven J Projan
    Department of Biological Technologies, Wyeth Research, Biological Technologies, 87 Cambridge Park Dr, Cambridge, MA 02140, USA
    Antimicrob Agents Chemother 51:1133-4. 2007
  9. pmc Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC beta-lactamase, and the foss of an outer membrane protein
    P A Bradford
    Wyeth Ayerst Research, Pearl River, New York 10965, USA
    Antimicrob Agents Chemother 41:563-9. 1997
    ..pneumoniae when a high level of the ACT-1 beta-lactamase is produced in combination with the loss of a major outer membrane protein...
  10. pmc Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci
    P M Dunman
    Infectious Diseases, Wyeth Ayerst Research, Pearl River, New York 10965, USA
    J Bacteriol 183:7341-53. 2001
    ....
  11. doi Francis Tally and the discovery and development of tigecycline: a personal reminiscence
    Steven J Projan
    Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA
    Clin Infect Dis 50:S24-5. 2010
    ..These included piperacillin-tazobactam (which is currently the injectable antibiotic with the largest volume of sales worldwide) and daptomycin. This article focuses on the discovery and development of tigecycline...
  12. pmc In vitro and in vivo activities of tigecycline (GAR-936), daptomycin, and comparative antimicrobial agents against glycopeptide-intermediate Staphylococcus aureus and other resistant gram-positive pathogens
    Peter J Petersen
    Infectious Disease Research Section, Wyeth Research, Bldg 200 Rm 3301, 401 N Middletown Road, Pearl River, NY 10965, USA
    Antimicrob Agents Chemother 46:2595-601. 2002
    ..These data suggest that tigecycline and daptomycin may offer therapeutic options against clinically relevant resistant pathogens for which current alternatives for treatment are limited...
  13. ncbi Inactivation of mprF affects vancomycin susceptibility in Staphylococcus aureus
    Alexey Ruzin
    Wyeth Research, Pearl River, NY 10965, USA
    Biochim Biophys Acta 1621:117-21. 2003
    ..This observation serves as a likely mechanism of the increased vancomycin susceptibility associated with mprF inactivation...
  14. pmc Establishment of in vitro susceptibility testing methodologies and comparative activities of piperacillin in combination with the penem {beta}-lactamase inhibitor BLI-489
    Peter J Petersen
    Infectious Disease Research, Wyeth Research, Pearl River, NY 10965, USA
    Antimicrob Agents Chemother 53:370-84. 2009
    ..The combination of piperacillin-BLI-489 also demonstrated improved activity compared to that of piperacillin-tazobactam against the problematic extended-spectrum beta-lactamase- and AmpC-expressing strains...
  15. pmc Further evidence that a cell wall precursor [C(55)-MurNAc-(peptide)-GlcNAc] serves as an acceptor in a sorting reaction
    Alexey Ruzin
    Department of Infectious Disease, Wyeth Ayerst Research, Pearl River, New York 10965, USA
    J Bacteriol 184:2141-7. 2002
    ..These results and those of additional experiments presented in this study further suggest that lipid II indeed serves as a natural substrate in a sorting reaction...
  16. ncbi Genomics in anti-infective drug discovery--getting to endgame
    Steven A Haney
    Wyeth Ayerst Research, 401 N Middletown Road, Pearl River, NY 10965, USA
    Curr Pharm Des 8:1099-118. 2002
    ....
  17. pmc A novel MATE family efflux pump contributes to the reduced susceptibility of laboratory-derived Staphylococcus aureus mutants to tigecycline
    Fionnuala McAleese
    Wyeth Research, 401 N Middletown Rd, Pearl River, NY 10965, USA
    Antimicrob Agents Chemother 49:1865-71. 2005
    ..These results suggest that the overexpression of mepA but not tet(M) may contribute to decreased susceptibility of tigecycline in S. aureus...
  18. ncbi Hydrophobic acetal and ketal derivatives of mannopeptimycin-alpha and desmethylhexahydromannopeptimycin-alpha: semisynthetic glycopeptides with potent activity against Gram-positive bacteria
    Russell G Dushin
    Wyeth Research, Chemical and Screening Sciences, Medicinal Chemistry, Pearl River, NY 10965, USA
    J Med Chem 47:3487-90. 2004
    ..The preferentially formed monofunctionalized 4,6-acetals and -ketals display potent antibacterial activities against Gram-positive microorganisms, including MRSA, PRSP, and VRE pathogens...
  19. pmc AcrAB multidrug efflux pump is associated with reduced levels of susceptibility to tigecycline (GAR-936) in Proteus mirabilis
    Melissa A Visalli
    Wyeth Research, Pearl River, New York, USA
    Antimicrob Agents Chemother 47:665-9. 2003
    ..The AcrAB transport system appears to be associated with the intrinsic reduced susceptibility to tigecycline in P. mirabilis...
  20. pmc Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1
    Charles R Dean
    Wyeth Research, Pearl River, New York 10965, USA
    Antimicrob Agents Chemother 47:972-8. 2003
    ..This suggests that glycylcyclines, although they are subject to efflux from P. aeruginosa, are generally inferior substrates for P. aeruginosa efflux pumps than are narrower-spectrum tetracyclines...
  21. ncbi Effect of srtA and srtB gene expression on the virulence of Staphylococcus aureus in animal models of infection
    William J Weiss
    Wyeth Research, 401 N Middletown Rd, Pearl River, NY 10965, USA
    J Antimicrob Chemother 53:480-6. 2004
    ..The role that the surface proteins anchored by the srtA and srtB gene products play in the ability of Staphylococcus aureus bacteria to establish infection was investigated in several animal models...
  22. pmc Uses of Staphylococcus aureus GeneChips in genotyping and genetic composition analysis
    P M Dunman
    Wyeth Research, 401 N Middletown Rd, Pearl River, NY 10965, USA
    J Clin Microbiol 42:4275-83. 2004
    ..aureus strains and may play a major role in epidemiological studies in the future where correlating genes with particular disease phenotypes is critical...
  23. pmc Identification and analysis of bacterial protein secretion inhibitors utilizing a SecA-LacZ reporter fusion system
    L E Alksne
    Wyeth Ayerst Research, Pearl River, New York 10965, USA
    Antimicrob Agents Chemother 44:1418-27. 2000
    ....
  24. pmc Use of ribotyping to retrospectively identify methicillin-resistant Staphylococcus aureus isolates from phase 3 clinical trials for tigecycline that are genotypically related to community-associated isolates
    Fionnuala McAleese
    Wyeth Research, Room 3301, Bldg 200, 401 N Middletown Rd, Pearl River, New York 10965, USA
    Antimicrob Agents Chemother 49:4521-9. 2005
    ....
  25. pmc SHV-7, a novel cefotaxime-hydrolyzing beta-lactamase, identified in Escherichia coli isolates from hospitalized nursing home patients
    P A Bradford
    Lederle Laboratories, Pearl River, New York, USA
    Antimicrob Agents Chemother 39:899-905. 1995
    ..This novel SHV-type extended-spectrum beta-lactamase is designated SHV-7...
  26. pmc Characterization of the Staphylococcus aureus heat shock, cold shock, stringent, and SOS responses and their effects on log-phase mRNA turnover
    Kelsi L Anderson
    Department of Pathology and Microbiology, University of Nebraska Medical Center, Nebraska 68198, USA
    J Bacteriol 188:6739-56. 2006
    ..aureus stress response-dependent alterations in transcript abundances can, in part, be attributed to alterations in RNA stability. This phenomenon was not observed within SOS-responsive cells...
  27. ncbi Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390
    James Cassat
    Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Microbiology 152:3075-90. 2006
    ....
  28. ncbi Whither antibacterial drug discovery?
    Steven J Projan
    Drug Discov Today 13:279-80. 2008
  29. ncbi Characterization of the Staphylococcus aureus CidR regulon: elucidation of a novel role for acetoin metabolism in cell death and lysis
    Soo Jin Yang
    Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, ID 83844 3052, USA
    Mol Microbiol 60:458-68. 2006
    ..The results of this study define the CidR regulon and demonstrate that the generation of acetoin is linked to the control of cell death and lysis in S. aureus...
  30. pmc Characterizing the effect of the Staphylococcus aureus virulence factor regulator, SarA, on log-phase mRNA half-lives
    Corbette Roberts
    Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198 6495, USA
    J Bacteriol 188:2593-603. 2006
    ..Based on the importance of the S. aureus agr RNA molecule, RNAIII, and small stable RNA molecules within other pathogens, it is possible that these RNA molecules influence biological processes within the organism...
  31. pmc Transcription Profiling of the mgrA Regulon in Staphylococcus aureus
    Thanh T Luong
    Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 W Markham St, Slot 511, Little Rock, AR 72205, USA
    J Bacteriol 188:1899-910. 2006
    ..The fact that a large number of genes are regulated by mgrA implies that MgrA is a major global regulator in S. aureus...
  32. pmc Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States
    Fred C Tenover
    Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
    J Clin Microbiol 44:108-18. 2006
    ..Comparative genomics between USA300-0114 and three other S. aureus lineages (USA100, USA400, and USA500) defined a set of USA300-0114-specific genes, which may facilitate the strain's pathogenesis within diverse environments...
  33. pmc Comparative genomics of Staphylococcus aureus musculoskeletal isolates
    James E Cassat
    Department of Microbiology and Immunology, Mail Slot 511, University of Arkansas for Medical Sciences, 4301 W Markham, Little Rock, AR 72205, USA
    J Bacteriol 187:576-92. 2005
    ..In contrast, RN6390, NCTC 8325, and COL formed a distinct cluster that, by comparison to the other four sequenced strains (Mu50, N315, MW2, and SANGER-476), was the most distantly related to the UAMS isolates and EMRSA-16...
  34. pmc Effect of mild acid on gene expression in Staphylococcus aureus
    Brian Weinrick
    Program in Molecular Pathogenesis, Skirball Institute, and Department of Microbiology, New York University School of Medicine, 540 First Ave, New York, NY 10016, USA
    J Bacteriol 186:8407-23. 2004
    ..Key results are verified by gene fusion and Northern blot hybridization analyses. The results point to, but do not define, possible regulatory pathways by which the organism senses and responds to a pH stimulus...
  35. pmc Global gene expression in Staphylococcus aureus biofilms
    Karen E Beenken
    Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 W Markham, Little Rock, AR 72205, USA
    J Bacteriol 186:4665-84. 2004
    ..A primary theme that emerged from the analysis of these genes is that persistence within a biofilm requires an adaptive response that limits the deleterious effects of the reduced pH associated with anaerobic growth conditions...
  36. ncbi Comparison of tetracycline and tigecycline binding to ribosomes mapped by dimethylsulphate and drug-directed Fe2+ cleavage of 16S rRNA
    Gesine Bauer
    Institut fur Mikrobiologie, Biochemie und Genetik, Universitat Erlangen, Erlangen, Germany
    J Antimicrob Chemother 53:592-9. 2004
    ..Here we analyse its mode of antibiotic action by probing 70S ribosomes of Escherichia coli with dimethylsulphate (DMS) and Fe(2+)-mediated cleavage to identify binding sites of tetracycline and tigecycline...
  37. ncbi Antimicrobials: new solutions badly needed
    Steven J Projan
    Curr Opin Microbiol 5:463-5. 2002
  38. ncbi Recurrent episodes of shock-like syndrome caused by the same strain of vancomycin-resistant Enterococcus faecium in a pediatric patient
    Laszlo Papp
    Department of Pediatrics, Weill Medical College of Cornell University, New York, NY 10021, USA
    Microb Drug Resist 9:307-12. 2003
    ..Recurrent VRE infections occur as a consequence of prolonged gastrointestinal colonization. Morbidity is associated with host factors, the presence of co-pathogens, and possibly intrinsically more virulent VRE strain...