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Clifford M. Snapper, M.D.

Director, Professor
E-mail: csnapper@usuhs.mil
Phone: 301-295-3490

Education:

1975		Brooklyn College, City University of New York, Brooklyn, NY – B.S. - Physics
1981		Albany Medical College of Union University, Albany, NY – MD - Medicine
1982		Certification, National Board of Medical Examiners
1985		Board Certification in Anatomic Pathology

Professional Positions:

1981-82		Intern, Internal Medicine, Albany Medical Center, Albany, NY
1982-85		Resident, Dept. of Pathology, The New York Hospital-Cornell Medical Center, New York, NY
1985-88		Medical Staff Fellow, Lab. of Immunology, NIAID, NIH, Bethesda, MD (Lab: William E. Paul)
1988-92		Assistant Professor, Dept of Pathology, USUHS, Bethesda, MD
1992-94		Associate Professor, Dept. of Pathology, USUHS, Bethesda, MD
1994-Pres		Professor, Dept. of Pathology, USUHS, Bethesda, MD
1994-Pres		Professor, Cell and Molecular Biology Program, USUHS, Bethesda, MD
1997-Pres		Professor, Dept. of Medicine, USUHS, Bethesda, MD
2000-Pres		Professor, Emerging Infectious Diseases Program, USUHS, Bethesda, MD
2000-Pres		Director, Institute for Vaccine Research, USUHS, Bethesda, MD

Honors/Awards/Appointments: B.S. Magna Cum Laude (1975), American Assoc. of Immunologists (1988), Burroughs Wellcome Fund Developing Investigator Award, Immunopharmacology of Allergic Diseases (1989), Associate Editor Journal of Immunology (1991-1993), The Jeffrey Modell Foundation Lifetime Achievement Award (1992), American Association of University Pathologists (1993), Editorial Board, Infection and Immunity (2004- ), Outstanding Biomedical Graduate Educator Award (USUHS, 2006), Section Editor, The Journal of Immunology (2009- ).

Research Projects Ongoing or Completed During the Last 3 Years:

• "Dendritic and T cells in anti-bacterial Ig responses", Principal Investigator: Clifford M. Snapper, M.D., Agency: NIH; Type: 2R01 AI049192-06; Period: 4/15/06-3/31/11; The role of this project is to elucidate the ability by which murine dendritic and T cells are able to process and present protein and polysaccharide antigens to the immune system for induction of antigen-specific Ig isotype production.
• "Novel Carrier for Polysaccharide Conjugates and an EBV Vaccine", Principal Investigator: Clifford M. Snapper, M.D., Agency NIH; Type R21 AI073627-01; Period: 12/15/2007-11/30/2009; The role of this project is to create an EBV vaccine and a potential carrier protein for anti-polysaccharide responses.
• "Developing of Novel Adjuvants for Augmenting Humoral Immunity", Principal Investigator: Clifford M. Snapper, M.D., Agency: USUHS; Period: 9/1/05-8/31/08; The role of this project is to develop novel approaches to augmenting protective antibody responses to protein and/or polysaccharide antigens, expressed by pathogens, for development of improved vaccines.
• "Toll-like Receptors and Anti-bacterial lg Responses "; Principal Investigator: Clifford M. Snapper, M.D., Agency: USUHS; Period: 10/1/06-9/30/09. The purpose of this grant is to determine the role of Toll-like receptors in mediating innate and adaptive immunity to Streptococcus pneumoniae.
• "Dengue virus vaccines and diagnostics"; Principal Investigator: Kanakatte Raviprakash, Ph.D., Agency: Office of Naval Research; Period: 10/1/05-9/30/08. The purpose of this project is to develop a protective, antibody-based tetravalent vaccine against dengue virus.

Selected Bibliography (48 out of 108 publications):

• Snapper, C.M., and Paul W.E. 1987. Interferon gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype expression. Science. 236:944.
• Snapper, C. M., Finkelman, F. D., and Paul, W.E. 1988. Differential regulation of IgG1 and IgE synthesis by interleukin 4. J. Exp. Med. 167:183.
• Snapper, C. M., Hornbeck, P. V., Atasoy, U., Pereira, G. M. B., Paul, W. E. 1988. Interleukin 4 induces membrane Thy-1 expression on normal murine B cells. Proc. Natl. Acad. Sci. USA. 85:6107.
• Snapper, C. M., Hooley, J. J., Urban, J. F., Jr., and Finkelman, F. D. 1991. Lack of FceRII expression by murine B cells after in vivo immunization is directly associated with Ig secretion and not Ig isotype switching. J. Immunol. 146:2161.
• Snapper, C. M., McIntyre, T. M., Mandler, R., Peçanha, L. M. T., Finkelman, F. D., Lees, A., and Mond, J. J. 1992. Induction of IgG3 secretion by IFN-g: A model for T cell-independent class switching in response to T cell-independent type-2 antigens. J. Exp. Med. 175:1367.
• Snapper, C. M., Yamada, H., Smoot, D., Sneed, R., and Mond, J. J. 1993. Comparative in vitro analysis of proliferation, Ig secretion, and Ig class switching by murine marginal zone and follicular B cells. J. Immunol. 150:2737.
• McIntyre, T. M., Klinman, D. R., Rothman, P., Lugo, M., Dasch, J. R., Mond, J. J., and Snapper, C. M. 1993. Transforming growth factor b1 selectively stimulates immunoglobulin G2b secretion by lipopolysaccharide-activated murine B cells. J. Exp. Med. 177:1031.
• Mandler, R., Chu, C., Paul, W. E., Max, E., and Snapper, C. M. 1993. Interleukin 5 induces Su-Sg1 DNA rearrangement by B cells activated with dextran-anti-IgD antibodies and interleukin-4: A 3 component model for Ig class switching. J. Exp. Med. 178:1577.
• Snapper, C. M., Yamaguchi, H., Sneed, R., Smoot, D., and Mond, J. J. 1993. Natural killer cells induce activated murine B cells to secrete Ig. J. Immunol. 151:5251.
• Snapper, C. M., Yamaguchi, H., Moorman, M. A., and Mond, J. J.. 1994. An in vitro model for T cell-independent induction of humoral immunity: A key role for natural killer cells. J. Immunol. 152:4884.
• Snapper, C. M., Kehry, M. R., Castle, B. E., and Mond, J. J. 1995. Multivalent, but not bivalent, antigen receptor crosslinkers synergize with CD40 ligand for induction of Ig synthesis and class switching in normal murine B cells. A redefinition of the TI-2 versus TD antigen dichotomy. J. Immunol. 154:1177.
• McIntyre, T. M., Kehry, and Snapper, C. M. 1995. Novel in vitro model for high-rate IgA class switching. J. Immunol. 154:3156.
• Snapper, C. M., Moorman, M. A. Kehry, M. R, Maliszewski, C. R., and Mond, J. J. 1995. IL-3 and GM-CSF strongly induce Ig secretion by sort-purified murine B cells activated through the membrane Ig, but not the CD40, signaling pathway. J. Immunol. 154:5842.
• Snapper, C. M., Rosas, F. R., Kehry, M. R., and Mond, J. J. 1995. Bacterial lipoproteins may substitute for cytokines in the humoral immune response to T cell-independent type II antigens. J. Immunol. 155:5582.
• Shparago, N., Zelazowski, P., Jin, L., McIntyre, T. M., Eckhard, S., Peçanha, L. M. T., Kehry, M. R., Mond, J. J., Max, E. E., and Snapper, C. M. 1996. Interleukin-10 selectively regulates murine Ig isotype switching. Int. Immunol. 8:781.
• Snapper, C. M., Moorman, M. A., Kehry, M. R., Mond, J. J., Maliszewski, C. R. 1996. IFN-g is a potent inducer of Ig secretion by B murine cells activated through the mIg-, but not CD40 signaling pathway. Int. Immunol. 8:877.
• Snapper, C. M. and Mond, J. J. 1996. A model for induction of T cell-independent humoral immunity in response to polysaccharide antigens. J. Immunol. 157: 2229.
• Snapper, C. M., Rosas, F. R., Zelazowski, P., Moorman, M. A., Kehry, M. R., Bravo, R., and Weih, F. 1996. B cells lacking relB are defective in proliferative responses, but undergo normal B cell maturation to Ig secretion and Ig class switching. J. Exp. Med. 184:1537.
• Snapper, C. M., Zelazowski, P., Rosas, F. R., Kehry, M. R, Baltimore, D., and Sha, B . 1996. B cells from p50/NF-kB knockout mice have selective defects in proliferation, differentiation, germline CH transcription and Ig class switching. J. Immunol. 156:183.
• Snapper, C. M., Marcu, K. B., and Zelazowski, P. 1997. Ig class switching: Beyond accessibility. Immunity. 6:217.
• Snapper, C. M., Rosas, F. R., Moorman, M. A., Kehry, M. R., and Mond, J. J. 1997. Restoration of T cell-independent type 2 induction of Ig secretion by murine neonatal B cells in vitro J. Immunol. 158:2731.
• Snapper, C. M., Rosas, F. R., Kehry, M. R., Mond, J. J., and Wetzler, L. M. 1997. Neisserial porins may provide critical second signals to polysaccharide-activated murine B cells for induction of Ig. Infect. Immun. 65:3203.
• Horwitz, B. H., Zelazowski, P., Shen, Y., Scott, M. L., Baltimore, D., and Snapper, C. M. 1999. The p65 subunit of NF-kB is redundant with p50 during B cell proliferative responses, and is required for germline CH transcription and class switching to IgG3. J. Immunol. 162:1941.
• Wu, Z-Q., Vos, Q., Shen, Y., Lees, A., Wilson, S. R., Briles, D. E., Gause, W. C., Mond, J. J., and Snapper, C. M. 1999. In vivo polysaccharide-specific IgG responses to intact Streptococcus pneumoniae are T cell-dependent and require CD40- and B7-ligand interactions. J. Immunol. 163:659.
• Wu, Z-Q, Khan, A. Q., Shen, Y., Schartmann, J., Peach, R., Lees, A., Mond, J. J., Gause, W. C., and Snapper, C. M. 2000. B7 requirements for primary and secondary protein- and polysaccharide-specific Ig isotype responses to Streptococcus pneumoniae. J. Immunol. 165:6840.
• Snapper, C. M., Shen, Y., Khan, A. Q., Colino, J., Zelazowski, P., Mond, J. J., Gause, W. C., and Wu, Z-Q. 2001. Distinct types of T-cell help for the induction of a humoral immune response to Streptococcus pneumoniae. Trends in Immunology. 22:308.
• Khan, A. Q., Shen, Y., Wu, Z-Q., Wynn, T. A., and Snapper, C. M. 2002. Endogenous pro-inflammatory and anti-inflammatory cytokines differentially regulate an in vivo humoral response to Streptococcus pneumoniae. Infect. Immun. 70:749.
• Colino, J., Shen, Y., and Snapper, C. M. 2002. Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein- and polysaccharide-specific immunoglobulin isotype responses in vivo through distinct mechanisms. J. Exp. Med. 195: 1.
• Wu, Z.-Q., Shen, Y., Chu, C-L., Riese, R., Chapman, H.A., Kanagawa, O., and Snapper, C. M. 2002. The mechanism underlying T cell help for induction of an antigen-specific in vivo humoral immune response to Streptococcus pneumoniae is dependent on the type of antigen. J. Immunol. 168: 5551.
• Wu, Z.-Q., Khan, A. Q., Shen, Y., Dawicki, W., Watts, T. H., Mittler, R. S., and Snapper, C. M. 2003. 4-1BB (CD137) differentially regulates murine in vivo protein- and polysaccharide-specific immunoglobulin isotype responses to Streptococcus pneumoniae. Infect. Immun. 71: 196.
• Colino, J. and Snapper, C. M. 2003.Opposing signals from Pathogen-Associated Molecular Patterns and IL-10 are critical for optimal dendritic cell induction of in vivo humoral immunity to Streptococcus pneumoniae. J. Immunol. 171: 3508.
• Colino, J. and Snapper, C. M. 2003. Two distinct mechanisms for induction of dendritic cell apoptosis in response to intact Streptococcus pneumoniae. J. Immunol. 171: 2354.
• Colino, J. and Snapper. C. M. 2003. Dendritic cells, new tools for vaccination. Microbes and Infection 5:311.
• Khan, A. Q., Lees, A., and Snapper, C. M. 2004. Differential regulation of IgG anti-capsular polysaccharide and anti-protein responses to intact Streptococcus pneumoniae in the presence of cognate CD4+ T cell help. J. Immunol. 172:532.
• Sen, G., Flora, M., Chattopadhyay, G., Klinman, D. M., Lees, A., Mond, J. J., and Snapper, C. M. 2004. The critical DNA flanking sequences of a CpG oligodeoxynucleotides, but not the 6 base CpG motif, can be replaced with RNA without quantitative or qualitative changes in Toll-like receptor 9-mediated activity. Cell. Immunol. 232: 64.
• Khan, A. Q., Chen, Q., Wu, Z-Q., Paton, J. C., and Snapper, C. M. 2005. Innate and type 1 humoral immunity to Streptococcus pneumoniae are both mediated by MyD88, but differ in their relative dependence on Toll-like receptor 2. Infect. Immun. 73:298.
• Lee, K. S., Sen, G., and Snapper, C. M. 2005. Endogenous CD4+CD25+ regulatory T cells (Tregs) play no apparent role in the acute humoral response to Streptococcus pneumoniae. Infect. Immun. In press.
• Sen, G, Khan, A. Q., Chen, Q., and Snapper, C. M. 2005. In vivo IgG responses to isolated pneumococcal polysaccharides are critically dependent on the presence of associated Toll-like receptor ligands. J. Immunol. 13:7084.
• Khan, A.Q., Sen, G., Guo, S., Witte, O.N., Snapper,C.M. 2006. Induction of CD4+ T cell-dependent IgG anti-polysaccharide (PS) responses to intact Streptococcus pneumoniae or to a soluble pneumococcal PS-protein conjugate is more heavily dependent on Btk-mediated BCR signaling than anti-protein responses. Infect. Immun. 74:1419.
• Sen, G., Chen, Q., and Snapper, C.M. 2006. Immunization of aged mice with a pneumococcal conjugate vaccine when combined with an unmethylated CpG-containing oligodeoxynucleotide restores defective IgG anti-PPS14 responses and PspA-specific CD4+ T cell priming to young adult levels. Infect. Immun. 74:2177.
• Colino, J, and Snapper, C. M. 2006. Exosomes from bone marrow dendritic cells pulsed with Diphtheria toxoid preferentially induce type 1 antigen-specific IgG responses in naïve recipients in the absence of free antigen. J. Immunol. 177: 3757
• Chen, Q., Sen, G., and Snapper, C. M. 2006. IL-1R1 is critical for cognate, but not non-cognate, CD4+ T cell help for induction of both type 1 and type 2 humoral immunity in response to intact Streptococcus pneumoniae. J. Immunol. 177: 6044.
• Colino, J., and Snapper, C. M. 2007. Dendritic cell derived exosomes express a Streptococcus pneumoniae capsular polysaccharide type 14 cross-reactive antigen that induces protective immunoglobulin responses against pneumococcal infection in mice. Infect. Immun. 75: 220.
• Goldblatt, D. and Snapper, C. M. 2007. Immunobiology of pneumococcal polysaccharides and conjugate vaccines. In. Pneumococcal Vaccines: The Impact of Conjugate Vaccine. Eds. G. Siber, K. Klugman, and H. Makela, ASM Press.
• Chattopadhyay, G., Khan, A. Q., Dubois, W., Potter, M., Snapper, C. M. 2007. Transgenic expressionof bcl-xL or bcl2 by murine B cells enhances the in vivo anti-polysacchardie, but not anti-protein response to intact Streptococcus pneumoniae. J. Immunol. 179: 7523.
• Vasilevsky, S., Colino, J., Puliaev, R., Canaday, D. H., and Snapper. C. M. 2008. Macrophages pulsed with Streptococcus pneumoniae elicit a T cell-dependent antibody response upon transfer into naïve mice. J. Immunol. 181:1787.
• Vasilevsky, S., Sen, G., Chattopadhyay, G., and Snapper, C. M. 2008. B and CD4+ T cell expression of TLR2 are critical for optimal induction of a T cell-dependent humoral immune response to intact Streptococcus pneumoniae.. Eur. J. Immunol. 38: 3316.
• Chattopadhyay, G., Chen, Q., Colino, J., Lees, A., and Snapper, C. M. 2009. Intact bacteria inhibit the induction of humoral immune responses to bacterial-derived and heterologous soluble T cell-dependent antigens. J. Immunol. 182: 2011.