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Richard Novick, M.D. Recanati Family Professor of Science, Departments of Microbiology (NYUSOM), Medicine (Pulm & CCM Div), and program in Molecular Pathogenesis (Skirball) Skirball Institute of Biomolecular Medicine, 2nd floor Labs 1 & 2 540 First Avenue, New York NY 10016 Office: (212) 263-6290 Lab: (212) 263-6294 Fax: (212) 263-5711 Email:
[email protected] KEYWORDS: Staphylococcus aureus; superantigens; mobile genes; pathogenicity islands, signal transduction, regulation of virulence, microbial pathogenesis; MRSA; bacterial genetics BIOGRAPHIC DETAILS: Medical Education:
MD with honors in microbiology, NYU School of Medicine, 1959
Postdoctoral Training:
National Institute for Medical Research, London, 1960-2; Rockefeller Institute, 1963-5
Academic Appointments:
1965-1981 Member, Public Health Research Institute; 1981-92 Director, Public Health Research Institute; 1993-present Investigator, Skirball Institute Program in Molecular Pathogenesis; Professor, Departments of Microbiology and Medicine
Major Responsibilities:
Laboratory Head
Major Honors:
Borden Award for Excellence in Undergraduate Research – 1959 Solomon Berson Medical Alumni Achievement Award – 1986 Fellow – American Association for the Advancement of Science – 1988 Fellow – American Academy of Microbiology – 1995 National Academy of Sciences - 2006 Master Researcher Award, NYUSOM 2008 Recanati Family Professor of Science – 2010-
RESEARCH INTERESTS: Our lab is focused on the study of staphylococcal virulence, its genetic and regulation. There are two major areas: 1. Global regulation of virulence genes by agr. Virulence in S. aureus is regulated by a complex network of regulatory determinants, the most important of which is the agr locus, which we have identified and characterized. The agr locus contains a two-component signaling module that is autoinduced by a small semi-cyclic peptide (AIP), that is encoded within the locus, is secreted, and then binds to AgrC, the signal receptor, activating the system. agr operates by autoinduction and is therefore a quorum sensor. Agr has undergone a striking evolutionary differentiation into 4 specificity groups in S. aureus. Heterologous AIPreceptor interactions are generally inhibitory, blocking virulence gene expression (but not growth). This inhibition has been shown to block an experimental abscess in mice. We are currently developing one of the inhibitory peptides for potential therapeutic use. Additionally, we are purifying the receptor in collaboration with the Skirball Structural Biology Group, in order to determine its structure which will reveal the mechanism of signal transduction. 2. Mobile pathogenicity islands encoding superantigens. Our second major area is the study of mobile, phagerelated pathogenicity islands (SaPIs) that encode and are responsible for the dissemination of genes encoding superantigens, such as toxic shock toxin and the enterotoxins. These elements, 15-20 kb in length, reside quiescently at specific chromosomal locations under the control of a repressor and are induced to excise and replicate by certain temperate phages, with which they severely interfere. Following replication, they are packaged in small, SaPI-induced infective phage-like particles that can infect other cells, thus spreading superantigen and other toxins. We have recently found that helper phages, but not non-helpers, produce specific bifunctional “moonlighting” proteins that induce SaPI reproduction by binding and inactivating the SaPI repressor. Current studies involve determination of the mechanism of SaPI interference with phage reproduction and identification of the SaPI genes involved. Additionally, we are very interested in similar elements carried by other bacteria, especially since an experiment to test for SaPI transfer to other species revealed efficient phage-mediated transfer, to Listeria monocytogenes, a serious food-borne pathogen, which is not known to produce superantigens. PUBLICATIONS: The phage-related chromosomal islands of Gram-positive bacteria. Novick RP, Christie GE, Penadés JR. Nat Rev Microbiol. 2010 Aug;8(8):541-51. Review. PMID: 20634809 Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands. Tormo-Más MA, Mir I, Shrestha A, Tallent SM, Campoy S, Lasa I, Barbé J, Novick RP, Christie GE, Penadés JR Nature. 2010 Jun 10;465(7299):779-82. PMID: 20634809 Symmetric signaling within asymmetric dimers of the Staphylococcus aureus receptor histidine kinase AgrC. George Cisar EA, Geisinger E, Muir TW, Novick RP Mol Microbiol.2009 Oct;74(1):44-57 PMID: 19708918 Specificity of staphylococcal phage and SaPI DNA packaging as revealed by integrase and terminase mutations Ubeda C, Olivarez NP, Barry P, Wang H, Kong X, Matthews A, Tallent SM, Christie GE, Novick RP Mol Microbiol. 2009 Apr;72(1):98-108 PMID: 19347993 agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides Geisinger E, Muir TW, Novick RP Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1216-21. Epub 2009 Jan 15 PMID: 19147840 Killing niche competitors by remote-control bacteriophage induction Selva L, Viana D, Regev-Yochay G, Trzcinski K, Corpa JM, Lasa I, Novick RP, Penadés JR Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1234-8. Epub 2009 Jan 13 PMID: 19141630 Phage-mediated intergeneric transfer of toxin genes Chen J, Novick RP Science. 2009 Jan 2;323(5910):139-41 PMID: 19119236 Quorum sensing in staphylococci Novick RP, Geisinger E Annu Rev Genet. 2008;42:541-64. Review PMID: 18713030 Regulatory organization of the staphylococcal sae locus Adhikari RP, Novick RP Microbiology. 2008 Mar;154(Pt 3):949-59 PMID: 18310041 Identification of ligand specificity determinants in AgrC, the Staphylococcus aureus quorum-sensing receptor Geisinger E, George EA, Muir TW, Novick RP J Biol Chem. 2008 Apr 4;283(14):8930-8. Epub 2008 PMID: 18222919 Sequence analysis reveals genetic exchanges and intraspecific spread of SaPI2, a pathogenicity island involved in menstrual toxic shock Subedi A, Ubeda C, Adhikari RP, Penadés JR, Novick RP Microbiology. 2007 Oct;153(Pt 10):3235-45 PMID: 17906123 Rational design of a global inhibitor of the virulence response in Staphylococcus aureus, based in part on localization of the site of inhibition to the receptor-histidine kinase, AgrC. Lyon GJ, Mayville P, Muir TW, Novick RP. Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13330-5. PMID: 11087872 Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. Mayville P, Ji G, Beavis R, Yang H, Goger M, Novick RP, Muir TW. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1218-23. PMID: 9990004 The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in Staphylococcus aureus Lindsay JA, Ruzin A, Ross HF, Kurepina N, Novick RP Mol Microbiol. 1998 Jul;29(2):527-43. PMID: 9720870 Bacterial interference caused by autoinducing peptide variants Ji G, Beavis R, Novick RP Science. 1997 Jun 27;276(5321):2027-30 PMID: 9197262 Cell density control of staphylococcal virulence mediated by an octapeptide pheromone Ji G, Beavis RC, Novick RP Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12055-9 PMID: 8618843 Replication-specific inactivation of the pT181 plasmid initiator protein. Rasooly A, Novick RP Science. 1993 Nov 12;262(5136):1048-50 PMID: 8235621 Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule Novick RP, Ross HF, Projan SJ, Kornblum J, Kreiswirth B, Moghazeh S EMBO J. 1993 Oct;12(10):3967-75 PMID: 7691599 Initiation of rolling-circle replication in pT181 plasmid: initiator protein enhances cruciform extrusion at the origin Noirot P, Bargonetti J, Novick RP Proc Natl Acad Sci U S A. 1990 Nov;87(21):8560-4 PMID: 2236066 pT181 plasmid replication is regulated by a countertranscript-driven transcriptional attenuator Novick RP, Iordanescu S, Projan SJ, Kornblum J, Edelman I. Cell. 1989 Oct 20;59(2):395-404 PMID: 2478296 Plasmid repopulation kinetics in Staphylococcus aureus Highlander SK, Novick RP. Plasmid. 1987 May;17(3):210-21 PMID: 2442785 Nosocomial transmission of a strain of Staphylococcus aureus causing toxic shock syndrome Kreiswirth BN, Kravitz GR, Schlievert PM, Novick RP Ann Intern Med. 1986 Nov;105(5):704-7 PMID: 3021039 On plasmid incompatibility Novick RP, Hoppensteadt FC Plasmid. 1978 Sep;1(4):421-34. Review. No abstract available PMID: 372974 LAB MEMBERS: Bo Shopsin Geeta Ram Krishan Kumar Brijesh Penugonda John Chen Dunrong Jiang Michael Engelbert Ivelisse Rodriguez Pagan Christoph Engl Hope Ross
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