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Thomas Jefferson University - Matthias J. Schnell, Ph.D.
Matthias J. Schnell, Ph.D.

Microbiology and Immunology
Director, Jefferson Vaccine Center
Professor, Department of Microbiology and Immunology
Mailing Address
233 South 10th St., 531 BLSB
Philadelphia, Pennsylvania 19107-5541
United States
Contact Information
Phone: 215-503-4634
Fax: 215-503-5393
Matthias.Schnell@jefferson.edu
Qualifications
B.S., M.S., Ph.D., University of Stuttgart-Hohenheim & Federal Research Center for Virus Diseases of Animals; Tuebingen, Germany, 1994
Expertise and Research Interests
Research interests of the laboratory are the development of novel vaccines and viral pathogenesis.

Vaccines: Our laboratory develops Rhabdovirus-based vectors as vaccines against other infectious diseases. We are particularly interested in using molecular adjuvants and other molecules to enhance antigen-specific immunity and manipulate and retarget immune cells.
Using different molecular approaches, we perform detailed studies of highly attenuated RVs expressing HIV-1 or SIV genes and analyze their immunogenicity in mice. Our most promising HIV vaccine candidates are currently being analyzed in a monkey model for AIDS.
Other approaches include using genetically modified RV G proteins or RV capsids to carry antigens of other pathogens as vaccines against Anthrax and Botulism.
We also seek to develop safer and more potent RV vaccines for wildlife and humans.

Pathogenesis: We are interested in understanding the interaction of rabies with the infected host at the molecular level. The molecular mechanism of rabies virus pathogenesis is not well understood, and our research analyzes the different functions of the rhabdoviral proteins (e.g. rabies virus) and their interactions with host proteins and the immune system.
Current projects are directed toward understanding:
- RV virus neurotropism and neuroinvasiveness: The transport of RV within neurons and the interaction of the RV phosphoprotein and glycoprotein with host proteins (receptors and transporter molecules)
- Immune responses of wild-type RV and RV-based vectors in the infected host (innate and adaptive)

Other Expertise
2003-present, different NIH special emphasis Study Sections, 2005-2008 permanent member NIH MID-B study section
2005-present member research committee IDSA
Convenor: American Society of Virology 2003, 2004, 2005, 2008
Editorial Boards: Journal of General Virology (2000-2005), Journal of Virology (2003-present).
Member: ASM, ASV, IDSA
Industrial Relevance
Design of novel vaccines against infectious diseases (HIV-1, Anthrax, Botulinum neurotoxin, and other infectious diseases)
Keywords
microbiology; biochemistry; immunology; molecular virology; vaccines; negative strand RNA viruses; rhabdoviruses; rabies virus; vesicular stomatitis virus; biodefense; HIV; SARS-CoV; anthrax; botulinum neurotoxin; neurovirology; neurotropic viruses; pathogenesis
Languages
English, German
Publications
  • Wirblich, C., Tan, G. S., Papaneri, A., Godlewski, P.J., Orenstein, J.M., Harty, R.N., Schnell, M.J. (2008). PPEY motif within the rabies virus (RV) matrix protein is essential for efficient virion release and RV pathogenicity. J. of Virol., in press

  • Weihe, E., Bette, M., Preuss, M. A., Faber, M., Schafer, M. K., Rehnelt, J., Schnell, M. J., and Dietzschold, B. (2008). Role of virus-induced neuropeptides in the brain in the pathogenesis of rabies. Dev Biol (Basel) 131, 73-81.

  • Snook, A. E., Stafford, B. J., Li, P., Tan, G., Huang, L., Birbe, R., Schulz, S., Schnell, M. J., Thakur, M., Rothstein, J. L., Eisenlohr, L. C., and Waldman, S. A. (2008). Guanylyl cyclase C-induced immunotherapeutic responses opposing tumor metastases without autoimmunity. J Natl Cancer Inst 100(13), 950-61.

  • Pulmanausahakul, R., Li, J., Schnell, M. J., and Dietzschold, B. (2008). The glycoprotein and the matrix protein of rabies virus affect pathogenicity by regulating viral replication and facilitating cell-to-cell spread. J Virol 82(5), 2330-8.

  • Li, J., McGettigan, J. P., Faber, M., Schnell, M. J., and Dietzschold, B. (2008). Infection of monocytes or immature dendritic cells (DCs) with an attenuated rabies virus results in DC maturation and a strong activation of the NFkappaB signaling pathway. Vaccine 26(3), 419-26.

  • Tan, G. S., Preuss, M. A., Williams, J. C., and Schnell, M. J. (2007). The dynein light chain 8 binding motif of rabies virus phosphoprotein promotes efficient viral transcription. Proc Natl Acad Sci U S A.

  • McKenna, P. M., Koser, M. L., Carlson, K. R., Montefiori, D. C., Letvin, N. L., Papaneri, A. B., Pomerantz, R. J., Dietzschold, B., Silvera, P., McGettigan, J. P., and Schnell, M. J. (2007). Highly Attenuated Rabies Virus-Based Vaccine Vectors Expressing Simian-Human Immunodeficiency Virus89.6P Env and Simian Immunodeficiency Virusmac239 Gag Are Safe in Rhesus Macaques and Protect from an AIDS-Like Disease. J Infect Dis 195(7), 980-8.

  • Li, J., McGettigan, J. P., Faber, M., Schnell, M. J., and Dietzschold, B. (2007). Infection of monocytes or immature dendritic cells (DCs) with an attenuated rabies virus results in DC maturation and a strong activation of the NFkappaB signaling pathway. Vaccine.

  • Faber, M., Faber, M. L., Li, J., Preuss, M. A., Schnell, M. J., and Dietzschold, B. (2007). Dominance of a nonpathogenic glycoprotein gene over a pathogenic glycoprotein gene in rabies virus. J Virol 81(13), 7041-7.

  • Dave, R. S., McGettigan, J. P., Qureshi, T., Schnell, M. J., Nunnari, G., and Pomerantz, R. J. (2006). siRNA targeting Vaccinia virus double-stranded RNA binding protein [E3L] exerts potent antiviral effects. Virology.

  • Li, J., Faber, M., Papaneri, A., Faber, M. L., McGettigan, J. P., Schnell, M. J., and Dietzschold, B. (2006). A single immunization with a recombinant canine adenovirus expressing the rabies virus G protein confers protective immunity against rabies in mice. Virology.

  • McGettigan, J. P., Koser, M. L., McKenna, P. M., Smith, M. E., Marvin, J. M., Eisenlohr, L. C., Dietzschold, B., and Schnell, M. J. (2006). Enhanced humoral HIV-1-specific immune responses generated from recombinant rhabdoviral-based vaccine vectors co-expressing HIV-1 proteins and IL-2. Virology 344(2), 363-77.

  • McKenna, P. M., Koser, M. L., Carlson, K. R., Montefiori, D. C., Letvin, N. L., Papaneri, A. B., Pomerantz, R. J., Dietzschold, B., Silvera, P., McGettigan, J. P., and Schnell, M. J. (2006). Highly attenuated rabies virus-based vaccine vectors expressing SHIV89.6P Env and SIVmac239 Gag are safe and immunogenic in rhesus macaques and protect from an AIDS-like disease. Journal of Infectious Diseases, accepted.

  • Plesa, G., McKenna, P. M., Schnell, M. J., and Eisenlohr, L. C. (2006). Immunogenicity of cytopathic and noncytopathic viral vectors. J Virol 80(13), 6259-66.

  • Smith, M. E., Koser, M., Xiao, S., Siler, C., McGettigan, J. P., Calkins, C., Pomerantz, R. J., Dietzschold, B., and Schnell, M. J. (2006). Rabies virus glycoprotein as a carrier for anthrax protective antigen. Virology.

  • Tang, J., Murtadha, M., Schnell, M., Eisenlohr, L. C., Hooper, J., and Flomenberg, P. (2006a). Human T-cell responses to vaccinia virus envelope proteins. J Virol 80(20), 10010-20.

  • Tang, J., Olive, M., Pulmanausahakul, R., Schnell, M., Flomenberg, N., Eisenlohr, L., and Flomenberg, P. (2006b). Human CD8+ cytotoxic T cell responses to adenovirus capsid proteins. Virology 350(2), 312-22.

  • Dietzschold, B., Schnell, M., and Koprowski, H. (2005). Pathogenesis of rabies. Curr Top Microbiol Immunol 292, 45-56.

  • Faber, M., Bette, M., Preuss, M. A., Pulmanausahakul, R., Rehnelt, J., Schnell, M. J., Dietzschold, B., and Weihe, E. (2005a). Overexpression of tumor necrosis factor alpha by a recombinant rabies virus attenuates replication in neurons and prevents lethal infection in mice. J Virol 79(24), 15405-16.

  • Faber, M., Faber, M. L., Papaneri, A., Bette, M., Weihe, E., Dietzschold, B., and Schnell, M. J. (2005b). A single amino acid change in rabies virus glycoprotein increases virus spread and enhances virus pathogenicity. J Virol 79(22), 14141-8.

  • Faber, M., Lamirande, E. W., Roberts, A., Rice, A. B., Koprowski, H., Dietzschold, B., and Schnell, M. J. (2005c). A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies. J Gen Virol 86(Pt 5), 1435-40.

  • Schnell, M. J., Tan, G. S., and Dietzschold, B. (2005). The application of reverse genetics technology in the study of rabies virus (RV) pathogenesis and for the development of novel RV vaccines. J Neurovirol 11(1), 76-81.

  • Tan, G. S., McKenna, P. M., Koser, M. L., McLinden, R., Kim, J. H., McGettigan, J. P., and Schnell, M. J. (2005). Strong cellular and humoral anti-HIV Env immune responses induced by a heterologous rhabdoviral prime-boost approach. Virology 331(1), 82-93.

  • McKenna, P. M., Aye, P. P., Dietzschold, B., Montefiori, D. C., Martin, L. N., Marx, P. A., Pomerantz, R. J., Lackner, A., and Schnell, M. J. (2004). Immunogenicity study of glycoprotein-deficient rabies virus expressing simian/human immunodeficiency virus SHIV89.6P envelope in a rhesus macaque. J Virol 78(24), 13455-9.

  • Koser, M. L., McGettigan, J. P., Tan, G. S., Smith, M. E., Koprowski, H., Dietzschold, B., and Schnell, M. J. (2004). Rabies virus nucleoprotein as a carrier for foreign antigens. Proc Natl Acad Sci U S A 101(25), 9405-10.

  • Irie, T., Licata, J. M., McGettigan, J. P., Schnell, M. J., and Harty, R. N. (2004). Budding of PPxY-containing rhabdoviruses is not dependent on host proteins TGS101 and VPS4A. J Virol 78(6), 2657-65.

  • Goodrich, A., Parveen, Z., Dornburg, R., Schnell, M. J., and Pomerantz, R. J. (2004). Spliced spleen necrosis virus vector RNA is not encapsidated: implications for retroviral replication and vector design. Mol Ther 9(4), 557-65.

  • Faber, M., Pulmanausahakul, R., Nagao, K., Prosniak, M., Rice, A. B., Koprowski, H., Schnell, M. J., and Dietzschold, B. (2004). Identification of viral genomic elements responsible for rabies virus neuroinvasiveness. Proc Natl Acad Sci U S A 101(46), 16328-32.

  • Dietzschold, M. L., Faber, M., Mattis, J. A., Pak, K. Y., Schnell, M. J., and Dietzschold, B. (2004). In vitro growth and stability of recombinant rabies viruses designed for vaccination of wildlife. Vaccine 23(4), 518-24.

  • Parveen, Z., Mukhtar, M., Rafi, M., Wenger, D. A., Siddiqui, K. M., Siler, C. A., Dietzschold, B., Pomerantz, R. J., Schnell, M. J., and Dornburg, R. (2003). Cell-type-specific gene delivery into neuronal cells in vitro and in vivo. Virology 314(1), 74-83.

  • McKenna, P. M., Pomerantz, R. J., Dietzschold, B., McGettigan, J. P., and Schnell, M. J. (2003a). Covalently linked human immunodeficiency virus type 1 gp120/gp41 is stably anchored in rhabdovirus particles and exposes critical neutralizing epitopes. J Virol 77(23), 12782-94.

  • McKenna, P. M., McGettigan, J. P., Pomerantz, R. J., Dietzschold, B., and Schnell, M. J. (2003b). Recombinant rhabdoviruses as potential vaccines for HIV-1 and other diseases. Curr HIV Res 1(2), 229-37.

  • McGettigan, J. P., Pomerantz, R. J., Siler, C. A., McKenna, P. M., Foley, H. D., Dietzschold, B., and Schnell, M. J. (2003a). Second-generation rabies virus-based vaccine vectors expressing human immunodeficiency virus type 1 gag have greatly reduced pathogenicity but are highly immunogenic. J Virol 77(1), 237-44.

  • McGettigan, J. P., Naper, K., Orenstein, J., Koser, M., McKenna, P. M., and Schnell, M. J. (2003b). Functional human immunodeficiency virus type 1 (HIV-1) Gag-Pol or HIV-1 Gag-Pol and env expressed from a single rhabdovirus-based vaccine vector genome. J Virol 77(20), 10889-99.

  • Dietzschold, B., Faber, M., and Schnell, M. J. (2003). New approaches to the prevention and eradication of rabies. Expert Rev Vaccines 2(3), 399-406.

  • Yan, X., Mohankumar, P. S., Dietzschold, B., Schnell, M. J., and Fu, Z. F. (2002). The rabies virus glycoprotein determines the distribution of different rabies virus strains in the brain. J Neurovirol 8(4), 345-52.

  • Wu, X., Gong, X., Foley, H. D., Schnell, M. J., and Fu, Z. F. (2002). Both viral transcription and replication are reduced when the rabies virus nucleoprotein is not phosphorylated. J Virol 76(9), 4153-61.

  • Siler, C. A., McGettigan, J. P., Dietzschold, B., Herrine, S. K., Dubuisson, J., Pomerantz, R. J., and Schnell, M. J. (2002). Live and killed rhabdovirus-based vectors as potential hepatitis C vaccines. Virology 292(1), 24-34.

  • McGettigan, J. P., McKenna, P. M., and Schnell, M. J. (2002). HIV-1 vaccines: the search continues. Clin Lab Med 22(3), 799-820, viii.

  • Foley, H. D., Otero, M., Orenstein, J. M., Pomerantz, R. J., and Schnell, M. J. (2002). Rhabdovirus-based vectors with human immunodeficiency virus type 1 (HIV-1) envelopes display HIV-1-like tropism and target human dendritic cells. J Virol 76(1), 19-31.

  • Faber, M., Pulmanausahakul, R., Hodawadekar, S. S., Spitsin, S., McGettigan, J. P., Schnell, M. J., and Dietzschold, B. (2002). Overexpression of the rabies virus glycoprotein results in enhancement of apoptosis and antiviral immune response. J Virol 76(7), 3374-81.

  • Dietzschold, B., and Schnell, M. J. (2002). New approaches to the development of live attenuated rabies vaccines. Hybrid Hybridomics 21(2), 129-34.

  • Harty, R. N., Brown, M. E., Hayes, F. P., Wright, N. T., and Schnell, M. J. (2001a). Vaccinia virus-free recovery of vesicular stomatitis virus. J Mol Microbiol Biotechnol 3(4), 513-7.

  • Harty, R. N., Brown, M. E., McGettigan, J. P., Wang, G., Jayakar, H. R., Huibregtse, J. M., Whitt, M. A., and Schnell, M. J. (2001b). Rhabdoviruses and the cellular ubiquitin-proteasome system: a budding interaction. J Virol 75(22), 10623-9.

  • Kulkosky, J., Culnan, D. M., Roman, J., Dornadula, G., Schnell, M., Boyd, M. R., and Pomerantz, R. J. (2001). Prostratin: activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART. Blood 98(10), 3006-15.

  • McGettigan, J. P., Foley, H. D., Belyakov, I. M., Berzofsky, J. A., Pomerantz, R. J., and Schnell, M. J. (2001a). Rabies virus-based vectors expressing human immunodeficiency virus type 1 (HIV-1) envelope protein induce a strong, cross-reactive cytotoxic T-lymphocyte response against envelope proteins from different HIV-1 isolates. J Virol 75(9), 4430-4.

  • McGettigan, J. P., Sarma, S., Orenstein, J. M., Pomerantz, R. J., and Schnell, M. J. (2001b). Expression and immunogenicity of human immunodeficiency virus type 1 Gag expressed by a replication-competent rhabdovirus-based vaccine vector. J Virol 75(18), 8724-32.

  • Morimoto, K., McGettigan, J. P., Foley, H. D., Hooper, D. C., Dietzschold, B., and Schnell, M. J. (2001a). Genetic engineering of live rabies vaccines. Vaccine 19(25-26), 3543-51.

  • Morimoto, K., Schnell, M. J., Pulmanausahakul, R., McGettigan, J. P., Foley, H. D., Faber, M., Hooper, D. C., and Dietzschold, B. (2001b). High level expression of a human rabies virus-neutralizing monoclonal antibody by a rhabdovirus-based vector. J Immunol Methods 252(1-2), 199-206.

  • Pulmanausahakul, R., Faber, M., Morimoto, K., Spitsin, S., Weihe, E., Hooper, D. C., Schnell, M. J., and Dietzschold, B. (2001). Overexpression of cytochrome C by a recombinant rabies virus attenuates pathogenicity and enhances antiviral immunity. J Virol 75(22), 10800-7.

  • Quinones-Kochs, M. I., Schnell, M. J., Buonocore, L., and Rose, J. K. (2001). Mechanisms of loss of foreign gene expression in recombinant vesicular stomatitis viruses. Virology 287(2), 427-35.

  • Schnell, M. J. (2001). Viral vectors as potential HIV-1 vaccines. FEMS Microbiol Lett 200(2), 123-9.

  • Foley, H. D., McGettigan, J. P., Siler, C. A., Dietzschold, B., and Schnell, M. J. (2000). A recombinant rabies virus expressing vesicular stomatitis virus glycoprotein fails to protect against rabies virus infection. Proc Natl Acad Sci U S A 97(26), 14680-5.

  • Morimoto, K., Foley, H. D., McGettigan, J. P., Schnell, M. J., and Dietzschold, B. (2000). Reinvestigation of the role of the rabies virus glycoprotein in viral pathogenesis using a reverse genetics approach. J Neurovirol 6(5), 373-81.

  • Schnell, M. J., Foley, H. D., Siler, C. A., McGettigan, J. P., Dietzschold, B., and Pomerantz, R. J. (2000). Recombinant rabies virus as potential live-viral vaccines for HIV-1. Proc Natl Acad Sci U S A 97(7), 3544-9.

  • Kahn, J. S., Schnell, M. J., Buonocore, L., and Rose, J. K. (1999). Recombinant vesicular stomatitis virus expressing respiratory syncytial virus (RSV) glycoproteins: RSV fusion protein can mediate infection and cell fusion. Virology 254(1), 81-91.

  • Schnell, M. J., Buonocore, L., Boritz, E., Ghosh, H. P., Chernish, R., and Rose, J. K. (1998). Requirement for a non-specific glycoprotein cytoplasmic domain sequence to drive efficient budding of vesicular stomatitis virus. Embo J 17(5), 1289-96.

  • Kim, S. K., Reed, D. S., Olson, S., Schnell, M. J., Rose, J. K., Morton, P. A., and Lefrancois, L. (1998). Generation of mucosal cytotoxic T cells against soluble protein by tissue-specific environmental and costimulatory signals. Proc Natl Acad Sci U S A 95(18), 10814-9.

  • Chenik, M., Schnell, M., Conzelmann, K. K., and Blondel, D. (1998). Mapping the interacting domains between the rabies virus polymerase and phosphoprotein. J Virol 72(3), 1925-30.

  • Schnell, M. J., Johnson, J. E., Buonocore, L., and Rose, J. K. (1997). Construction of a novel virus that targets HIV-1-infected cells and controls HIV-1 infection. Cell 90(5), 849-57.

  • Kretzschmar, E., Buonocore, L., Schnell, M. J., and Rose, J. K. (1997). High-efficiency incorporation of functional influenza virus glycoproteins into recombinant vesicular stomatitis viruses. J Virol 71(8), 5982-9.

  • Johnson, J. E., Schnell, M. J., Buonocore, L., and Rose, J. K. (1997). Specific targeting to CD4+ cells of recombinant vesicular stomatitis viruses encoding human immunodeficiency virus envelope proteins. J Virol 71(7), 5060-8.

  • Kretzschmar, E., Peluso, R., Schnell, M. J., Whitt, M. A., and Rose, J. K. (1996). Normal replication of vesicular stomatitis virus without C proteins. Virology 216(2), 309-16.

  • Mebatsion, T., Schnell, M. J., Cox, J. H., Finke, S., and Conzelmann, K. K. (1996). Highly stable expression of a foreign gene from rabies virus vectors. Proc Natl Acad Sci U S A 93(14), 7310-4.

  • Schnell, M. J., Buonocore, L., Kretzschmar, E., Johnson, E., and Rose, J. K. (1996a). Foreign glycoproteins expressed from recombinant vesicular stomatitis viruses are incorporated efficiently into virus particles. Proc Natl Acad Sci U S A 93(21), 11359-65.

  • Schnell, M. J., Buonocore, L., Whitt, M. A., and Rose, J. K. (1996b). The minimal conserved transcription stop-start signal promotes stable expression of a foreign gene in vesicular stomatitis virus. J Virol 70(4), 2318-23.

  • Schnell, M. J., and Conzelmann, K. K. (1995). Polymerase activity of in vitro mutated rabies virus L protein. Virology 214(2), 522-30.

  • Mebatsion, T., Schnell, M. J., and Conzelmann, K. K. (1995). Mokola virus glycoprotein and chimeric proteins can replace rabies virus glycoprotein in the rescue of infectious defective rabies virus particles. J Virol 69(3), 1444-51.

  • Schnell, M. J., Mebatsion, T., and Conzelmann, K. K. (1994). Infectious rabies viruses from cloned cDNA. Embo J 13(18), 4195-203.

  • Conzelmann, K. K., and Schnell, M. (1994). Rescue of synthetic genomic RNA analogs of rabies virus by plasmid-encoded proteins. J Virol 68(2), 713-9.

  • Wagner, J. A., Schnell, M., and Frank, W. (1988). [The occurrence of Trichinella in indigenous wildlife]. Berl Munch Tierarztl Wochenschr 101(12), 413-6.

Individual Expertise profile of Matthias J. Schnell, Ph.D., Copyright © Matthias J. Schnell, Ph.D..
Last Updated by Matthias Schnell, Ph.D. : Thursday, July 24, 2008 1:31:16 PM



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