Leib Lab / CV & Publications

Curriculum Vitae - David Anthony Leib

Address:
  • Washington University School of Medicine
  • Department of Ophthalmology and Visual Sciences
  • 660 S. Euclid Ave. Campus Box 8096
  • St. Louis, MO 63110
  • (314) 362-2689 office
  • (314) 362-3638 FAX
  • leib@vision.wustl.edu
Present Positions:
  • Professor, Department of Ophthalmology and Visual Sciences
  • Professor, Department of Molecular Microbiology

Education:
1983

BSc 2(i) Hons: School of Biological Sciences
The University of Birmingham, Birmingham, UK
1986

Ph.D.: Postgraduate student in the laboratory of Prof. Kevin McCarthy
Department of Medical Microbiology,
The University of Liverpool, Liverpool, UK

Postdoctoral Training:
1987 - 1990

Research Fellow in the laboratory of Dr. Priscilla Schaffer,
Department of Microbiology and Molecular Genetics,
Harvard Medical School, Boston, MA, USA

Academic Appointments:
1990 - 1998

Assistant Professor, Depts. of Ophthalmology and Visual Sciences, Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
1998 - 2004

Associate Professor, Department of Ophthalmology and Visual Sciences
2000 - 2004

Associate Professor, Department of Molecular Microbiology
2004 -

Professor, Depts. of Ophthalmology and Visual Sciences, & Molecular Microbiology

Awards, Fellowships and Honors:
1983 - 86

DH Mills Postgraduate Studentship in Medicine
1987 - 90

National Multiple Sclerosis Society Postdoctoral Fellowship
1988

1998 Research to Prevent Blindness Robert E. McCormick Scholarship
1999, 2002

Washington University Distinguished Service Teaching Awards
2001

Glaxo Smith-Kline Invited Professorship, University of Utah
2003

Research to Prevent Blindness Lew R. Wasserman Merit Award

Current Research Support:
1992 - 2008

NEI RO1, Principal Investigator, Continuous funding from 1992-2008 "Viral and host factors in herpetic reactivation"
1994 - 2006

NEI RO1, Principal Investigator, Continuous funding from 1994-2006 "HSV-induced RNA degradation in pathogenesis"

2002 - 2006

NEI RO3 2002-2006, Principal Investigator "Bacterial Artificial Chromosomes for HSV Genomics"

Current Committee and Teaching Responsibilities:

  • Member: Molecular Microbiology & Microbial Pathogenesis Program Steering Committee, 1993-Present.
  • Member: Washington University Department of Ophthalmology, Research Executive Committee, 2002-present.
  • Member: Vision Sciences Training Grant Steering Committee 2002-present.
  • Co-coursemaster: Molecular Virology Journal Club (L41 5393 Biol).
  • Co-coursemaster: "Molecular Basis of Microbial Pathogenesis" (Bio 5217)
  • Lecturer: "Molecular Microbiology & Pathogenesis" (Bio 5392), "Molecular Basis of Microbial Pathogenesis" (Bio 5217).

Past PhD Thesis Advisees:

  • Dr. Lisa Strelow, Research Assistant Professor, UC Davis, Center for Comparative Medicine
  • Dr. David Davido, Assistant Professor, University of Kansas, Dept. of Molecular Biosciences
  • Dr. Bretton Summers, postdoctoral associate, ChemoCentryx Inc., San Carlos, CA
  • Dr. Stephanie Strand, postdoctoral fellow with Dr William Goldman, Washington University
  • Dr. Stephen Ward, postdoctoral fellow with Dr. Barbara Burleigh, Harvard University

Peer Review Service:
2003 - 2008

Editorial Board Member, Journal of Virology.
2003 - 2006

Permanent Study Section Member, NIAID,Virology B.
2005 -

Editorial Advisory Panel, Future Virology.
2006

Member of Faculty of 1000 Biology.
 

Ad hoc Study Section Member: NIH NINDS (Neurological Sciences and Disorders), NIH NIAID (Virology), American Cancer Society (Molecular & Cell Biology of Cancer), The US-Israel Science Foundation.
 

Ad hoc reviewer for American Journal of Ophthalmology, Archives of Virology, BioEssays, BioTechniques, Cellular Microbiology, Cornea, Experimental Eye Research, Investigative Ophthalmology and Visual Science, Journal of Biotechnology, Journal of Clinical Investigation, Journal of Experimental Medicine, Journal of General Virology, Journal of Infectious Diseases, Molecular Genetics & Metabolism, Virology.

Peer Reviewed Publications:

  1. Leib, D.A., Bradbury, J.M., Gaskell, R.M., Hughes, C.J. and Jones, R.C. (1986). Restriction endonuclease patterns of some European and American isolates of avian infectious laryngotracheitis virus. Avian Diseases 30, 835-837.
  2. Leib, D.A., Hart, C.A. and McCarthy, K. (1987). Characterization of four herpesviruses isolated from owl monkeys and their comparison with Herpesvirus saimiri type 1 (Herpesvirus tamarinus) and herpes simplex virus type 1. Journal of Comparative Pathology 97, 159-169.
  3. Leib, D.A., Bradbury, J.M., Hart, C.A. and McCarthy, K. (1987). Genome isomerism in two alphaherpesviruses: Herpesvirus saimiri-1 (Herpesvirus tamarinus) and avian infectious laryngotracheitis virus. Archives of Virology 93, 287-294.
  4. Leib, D.A., Hart, C.A. and McCarthy, K. (1988). Alphaherpesvirus saimiri in rabbits: A model for human encephalitis? Journal of General Virology 69, 1609-1615.
  5. Mossman, S.P., Leib, D.A., McCarthy, K. and Hart, C.A. (1989). The effects of 5-azacytidine, 12-0-tetradecanoylphorbol-13-acetate and sodium-butyrate on reactivation of a Herpesvirus saimiri from explant cultures of latently infected dorsal root ganglia. Journal of General Virology, 70, 2507-2512.
  6. Leib, D.A., Coen, D.M., Bogard, C.L., Hicks, K.A., Yager, D.R., Knipe, D.M., Tyler, K.L. and Schaffer, P.A. (1989). Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency. Journal of Virology 63, 759-768.
  7. Leib, D.A., Bogard, C.L., Kosz-Vnenchak, M., Hicks, K.A., Coen, D.M., Knipe, D.M. and Schaffer, P.A. (1989). A deletion mutant of the latency associated transcript (LAT) of herpes simplex virus reactivates from the latent state with reduced frequency. Journal of Virology, 63, 2893-2900.
  8. Coen, D.M., Kosz-Vnenchak, M., Jacobson, J.G., Leib, D.A., Bogard, C.L., Schaffer, P.A., Tyler, K.L. and Knipe, D.M. (1989). Thymidine kinase negative herpesvirus mutants establish latency in mouse trigeminal ganglia, but do not reactivate. Proceedings of the National Academy of Sciences, 86, 4736-4740.
  9. Jacobson, J.G., Leib, D.A., Goldstein, D.J., Bogard, C.L., Schaffer, P.A., Weller, S.K. and Coen, D.M. (1989). A herpes simplex virus ribonucleotide reductase deletion mutant is defective for productive, acute and reactivatable latent infections of mice and for replication in mouse cells. Virology, 173, 276-283.
  10. Leib, D.A., Ruffner, K., Hildebrand, C., Schaffer, P.A., Wright, G. and Coen, D.M. (1990). Specific inhibitors of herpes simplex virus thymidine kinase diminish reactivation of latent virus from explanted ganglia. Antimicrobial Agents and Chemotherapy, 34, 1285-1286.
  11. Leib, D.A., Nadeau, K.C., Rundle, S.A. and Schaffer, P.A. (1991). The promoter of the latency-associated transcripts of herpes simplex virus type 1 contains a functional cAMP response element: The role of the latency-associated transcripts and cAMP in the reactivation of viral latency. Proceedings of the National Academy of Sciences, 88, 48-52.
  12. Rader, K. A., Ackland-Berglund, C., Miller, J., Pepose, J., and Leib, D.A. (1993). In vivo characterization of site-directed mutants in the promoter of the latency-associated transcripts. Journal of General Virology, 74, 1859-1869.
  13. Strelow, L.I., Laycock, K.A., Jun, P.J., Rader, K.A., Brady, R.H., Miller, J.K., Pepose, J. S., and Leib, D.A. (1994). A structural and functional comparison of the LAT promoters of herpes simplex virus type 1 (HSV-1) strains KOS and McKrae. Journal of General Virology, 75, 2475-2480.
  14. Kaplitt, M.G., Tjuvajev, J.G., Leib, D.A., Berk, J., Pettigrew, K.D., Posner, J.B., Pfaff, D.W., Rabkin, S.D., Blasberg, R.G. (1994). Mutant herpes simplex virus induced regression of tumors growing in immunocompetent rats. Journal of Neuro-Oncology. 19:137-47.
  15. Ackland-Berglund, C. and Leib, D.A. (1995) The efficacy of tetracycline-controlled gene expression is influenced by cell type. BioTechniques, 18: 196-200. (Also commentary in BioTechniques 19: 216-217).
  16. Ackland-Berglund, C., Davido, D. J., and Leib, D.A. (1995). The roles of the cAMP-response element and TATA box in expression of the herpes simplex virus type 1 latency associated transcripts. Virology, 210: 141-151.
  17. Strelow, L.I. and Leib, D.A. (1995). Role of the virion host shutoff (vhs) of herpes simplex virus type 1 in latency and pathogenesis. Journal of Virology, 69: 6779-6786.
  18. Strelow, L.I. and Leib, D.A. (1996). Analysis of conserved domains of UL41 of herpes simplex virus type 1 in virion host shutoff and pathogenesis. Journal of Virology, 70: 5665-5667.
  19. Davido, D.J. and Leib, D.A. (1996). Role of cis-acting sequences of the ICP0 promoter of herpes simplex virus type 1 in viral pathogenesis, latency and reactivation. Journal of General Virology, 77:1853-1863.
  20. Strelow, L.I., Smith, T., and Leib, D.A. (1997). The virion host shutoff function of herpes simplex virus type 1 plays a role in corneal invasion and functions independently of the cell cycle. Virology, 231:28-34.
  21. Walker J. and Leib, D.A. (1998). Protection from primary infection and establishment of latency by vaccination with herpes simplex virus type 1 recombinants deficient in the virion host shutoff (vhs) function. Vaccine, 16: 1-5.
  22. Walker, J. Laycock, K.A., Pepose, J.S., and Leib, D.A. (1998). Postexposure vaccination with a virion host shutoff defective mutant reduces UV-B radiation-induced ocular herpes simplex virus shedding in mice. Vaccine, 16: 6-8.
  23. Jun, P.Y., Strelow, L.I., Herman, R.C., Marsden, H.S., Eide, T., Haar, L., and Leib, D.A. (1998). The UL4 gene of herpes simplex virus type 1 is dispensible for latency, reactivation and pathogenesis in mice. Journal of General Virology, 79: 1603-1611.
  24. Davido, D.J. and Leib, D.A. (1998). Analysis of the basal and inducible activites of the ICP0 promoter of herpes simplex virus type 1. Journal of General Virology, 79:2093-2098.
  25. Eide, T., Marsden, H., Leib, D.A., Cunninghan, C., Davidson, A.J., Langeland, N., and Haar, L. (1998). Identification of the UL4 protein product of herpes simplex virus type 1. Journal of General Virology, 79: 3033-3038.
  26. Leib, D.A., Harrison, T.E., Laslo, K.M., Machalek, M.A., Moorman, M.J., and Virgin. H.W. (1999). Interferons regulate the phenotype of wild-type and mutant herpes simplex viruses in vivo. The Journal of Experimental Medicine, 189:663-672.
  27. Smith, T.J., Ackland-Berglund, C.E., and Leib, D.A. (2000). Herpes simplex virus virion host shutoff activity alters periocular disease in mice. Journal of Virology, 74:3598-3604.
  28. D.A. Leib., M.A. Machalek, B.R. Williams, R.H. Silverman, and H.W. Virgin. (2000) Specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene. Proceedings of the National Academy of Sciences, 67:6097-6101.
  29. Geiss, B.M., Smith, T.J., Leib, D.A. and Morrison, L.A. (2000). Disruption of virion host shutoff activity improves the immunogenicity and protective capacity of a replication-incompetent herpes simplex virus 1 vaccine strain. Journal of Virology, 74:11137-11144.
  30. Summers, B.C., Margolis, T.P., and Leib, D.A. (2001). Herpes simplex virus results in periocular disease by zosteriform spread. Journal of Virology, 75: 5069-5075.
  31. Mohr, I., Sternberg, D., Ward, S., Leib, D., Mulvey, M., and Gluzman, Y. (2001). An HSV-1 ?34.5 second-site supressor mutant that inhibits enhanced growth in cultured glioblastoma cells is severely attenuated in animals. Journal of Virology, 75: 5189-5196.
  32. Geiss, B.J., Tavis, J.E., Lisa M. Metzger, L.M., Leib, D.A., and Morrison, L.A. (2001) Temporal regulation of HSV-2 VP22 expression and phosphorylation. Journal of Virology, 75: 10721-10729.
  33. Davido, D.J., Leib, D.A., and Schaffer, P.A. (2002). The cyclin-dependent kinase inhibitor, roscovitine, regulates the transactivating activity and post-translational modification of herpes simplex virus type 1 ICP0. Journal of Virology, 76:1077-1088.
  34. Talloczy, Z, Jiang, W., Virgin, H.W., Leib, D.A., Scheuner, D, Kaufman, R.J., Eskelinen, E., Levine, B. (2002). Regulation of autophagy by the yeast and mammalian eIF-2? kinase pathway. Proceedings of the National Academy of Sciences, 99: 190-195.
  35. Smith, T.J., Morrison, L.M., and Leib, D.A. (2002). Pathogenesis of an HSV-2 recombinant deleted in the virion host shutoff protein. Journal of Virology, 76: 2054-2061.
  36. Summers, B.C. and Leib, D.A. (2002). Herpes simplex virus type 1 origins of DNA replication play no role in the regulation of flanking promoters. Journal of Virology, 76: 7020-7029.
  37. Keadle, T.L., Laycock, K.A., Walker, J.L., Leib, D.A., Morrison, L.A., Pepose, J.S., and Stuart, P.M. (2002). Therapeutic vaccination with vhs- herpes simplex virus (HSV) reduces the severity of recurrent herpetic stromal keratitis in mice. Journal of General Virology 83: 2361-2365.
  38. Luker, G.D., Bardill, J.P., Prior, J.L., Pica, C.M., Piwnica-Worms, D., and Leib, D.A. (2002). Non-invasive bioluminescence imaging of herpes simplex virus type 1 (HSV-1) infection and therapy in living mice. Journal of Virology, 76: 12149-12161.
  39. Smith, T.J., Silverman, R.H., and Leib, D.A. (2003). RNase L activity does not contribute to host RNA degradation induced by herpes simplex virus infection. Journal of General Virology, 84: 925-928.
  40. Ward, S.L., Scheuner, D., Kaufman, R.J., Mohr, I, and Leib, D.A. (2003). In vivo replication of an ICP34.5 second-site suppressor mutant following corneal infection correlates with in vitro regulation of eIF2? phosphorylation. Journal of Virology, 77: 4626-4634.
  41. Luker, G.D., Prior, J.L., Song, J., Pica, C.M., and Leib, D.A. (2003). Bioluminescence imaging reveals systemic dissemination of HSV-1 in the absence of interferon receptors. Journal of Virology 77:11082-11093.
  42. Krug, A., Luker, G.D., Barchet, W., Leib, D.A., Akira, S., and Colonna, M. (2004) Herpes Simplex Virus type 1 (HSV-1) activates Natural Interferon-Producing cells (IPC) through Toll-Like Receptor 9. Blood, 15:1433-1437.
  43. Stuart, P.M., Summers, B.C., Morris, J.E., Morrison, L.M., and Leib, D.A. (2004) CD8 T cells control corneal disease following ocular infection with HSV-1. Journal of General Virology, 85: 2055-2063.
  44. Strand, S.S., VanHeyningen, T.K., and Leib, D.A. (2004) The virion host shutoff protein of HSV-1 shows RNA degradation activity in primary neurons. Journal of Virology 78: 8400-8403.
  45. Strand, S.S. and Leib, D.A. (2004) Studies of the role of the VP16-binding domain of vhs in viral growth, host shutoff, activity and pathogenesis. Journal of Virology, 78:13562-13572.
  46. Luker, G.D., and Leib, D.A. (2005). Luciferase real time bioluminescence imaging for the study of viral pathogenesis. Methods in Molecular Biology 292: 285-296.
  47. Luker, K.E., Schultz, T.,Romine, J., Leib, D.A., Luker, G.D. (2006). Transgenic reporter mouse for bioluminescence imaging of herpes simplex virus-1 infection in living mice. Virology. 2006 347:286-295.
  48. Pasieka TJ, Baas T, Carter VS, Proll SC, Katze MG, Leib DA.Functional genomic analysis of herpes simplex virus type 1 counteraction of the host innate response. J Virol. 2006 Aug;80(15):7600-7612.
  49. Gierasch WW, Zimmerman DL, Ward SL, Vanheyningen TK, Romine JD, Leib DA. Construction and characterization of bacterial artificial chromosomes containing HSV-1 strains 17 and KOS.J Virol Methods. 2006 Aug;135(2):197-206.
  50. Lenschow , D.J., Lai, C., Frias-Staheli, N., Giannakopoulos , N.V., Lutz, A., Wolff, T., Osiak, A., Levine, B., Schmidt, R.E., Garcia-Sastre,A., Leib, D.A., Pekosz,A.S., Knobeloch, K., Horak, I., and Virgin, H.W. (2007). ISG15 functions as a critical antiviral molecule against influenza, herpes and sindbis viruses. Proceedings of the National Academy of Sciences, 104: 1371-1376.
  51. Orvedahl, A., Alexander, D., Tallóczy, Z., Sun, Q., Zhang, W., Wei, Y., Burns, D., Leib, D.A.,Levine, B. (2007). The HSV-1-encoded protein, ICP34.5, confers neurovirulence by targeting the mammalian autophagy protein, beclin 1. Cell Host and Microbe, 1:23-35.
  52. Margolis, T.P., Elfman, F.L., Leib, D.A., Pakpour, N., Apakupakul, K., and Voytek, C. (2007). Spontaneous reactivation of HSV-1 in latently infected murine sensory ganglia. Journal of Virology, 81: 11069-11074.
  53. Alexander, D.A., Ward, S.L., Mizushima, N., Levine, B, and Leib, D.A. (2007). Analysis of the role of autophagy in control of herpes simplex virus replication in cell culture. Journal of Virology, 81: 12128-12134.
  54. Pasieka TJ, Lu B, Crosby SD, Wylie KM, Morrison LA, Alexander DE, Menachery VD, Leib DA. Herpes simplex virus virion host shutoff attenuates establishment of the antiviral state. J Virol. 2008 Mar 26; [Epub ahead of print]
  55. Pasieka T, Lu B, Leib DA Enhanced Pathogenesis of an Attenuated Herpes Simplex Virus in Mice Lacking Stat1. J Virol. 2008 Apr 9; [Epub ahead of print]

Invited Review Articles and Book Chapters

  1. Olivo, P.D. and Leib, D.A. (1993). Gene delivery to neurons: Is herpes simplex virus the right tool for the job? BioEssays, 15, 547-554.
  2. Leib, D.A. (1994). Experimental strategies for the prevention of herpes simplex virus reactivation. International Antiviral News, 2, 39-40.
  3. Pepose, J.S. and Leib, D.A. (1994). Herpes simplex viral vectors for therapeutic gene delivery to ocular tissues. Investigative Ophthalmology and Visual Science 34, 2662-2665.
  4. Pepose, J.S., Leib, D.A., Stuart, P.M., and Easty, D.L. (1996). Herpes simplex virus diseases: Anterior segment of the eye. In: Ocular Infection and Immunity, Eds. J.S. Pepose, G. N. Holland, and K.R. Wilhelmus. Mosby-Year Book Inc., St. Louis MO, pp 905-932.
  5. Leib, D.A. (2000). Genetic engineering of animal DNA viruses in order to study and modify pathogenesis. In: Genetically Engineered Viruses: Development and Applications. Eds. C.J. Ring and E.D. Blair. BIOS Scientific Publishers, Oxford, UK, pp 159-186.
  6. Leib, D.A. (2002). Herpes simplex virus interference with interferon responses. In: Viral Proteins Counteracting Host Defenses. Ed. U.H. Koszinowski, Current Topics in Microbiology and Immunology, Springer Verlag, Heidelberg, Germany pp 171-185.
  7. Alexander, D.E. and Leib, D.A. (2008). Xenophagy in herpes simplex virus replication and pathogenesis. Autophagy, 4: 101-103.

Patent

Herpes simplex virus mutants" US Patent number 5698431 issued 12/16/97. Patent covers use of vhs-deficient HSV mutants as live attenuated vaccines and establishes vhs as a target for antiviral chemotherapy. Patent filed through the Washington University/Monsanto/GD Searle Biomedical Agreement.


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