Mark Slifka, Ph.D.

Mark K. Slifka
In their search for new and more effective vaccines, scientists are still unraveling the intricacies of those operations of the immune system that protect us from microbial infection. By understanding the mechanisms involved with improving T cell and B cell responses to foreign antigens, we will be able to develop more effective vaccines against viruses and other microbial pathogens.
Mark Slifka and his colleagues are investigating the underlying mechanisms of humoral and cell-mediated immunity against acute viral infections. This work has included developing several models of acute viral infection and/or vaccination in order to address basic immunological questions related to the development and maintenance of long-term protective immunity. We have also developed a series of clinical studies in which we study immunological memory directly in human subjects. During the course of this work, we study a number of viruses including arenaviruses (lymphocytic choriomeningitis virus, LCMV), flaviviruses (yellow fever virus and West Nile virus), and orthopoxviruses (vaccinia, cowpox, and monkeypox). The combination of basic research in animal models and applied research in clinical studies involving both healthy and immunocompromised populations has provided the opportunity to better define the requirements for immunological memory and to learn how to develop more effective diagnostics and vaccine candidates.

These experiments lay the foundation for future studies in which Slifka and team members will develop new antiviral vaccines and determine the mechanisms involved with building strong vaccine-induced immunity. For instance, these scientists have recently discovered a new approach to vaccine production that results in a safer, more effective vaccine preparation that can be used to create better human and animal vaccines that will require fewer booster vaccinations in order to maintain protective immunity for a prolonged period of time.

Biography

After graduating from Washington State University with a B.S. degree in microbiology and molecular biology in 1992 and from the UCLA School of Medicine with a Ph.D. in microbiology and immunology in 1996, Mark Slifka became a postdoctoral fellow in the department of neuropharmacology at the Scripps Research Institute in La Jolla. He came to the OHSU Vaccine and Gene Therapy Institute as an assistant professor and to ONPRC as an affiliate assistant scientist in 2001 and was promoted to associate professor in 2006.

Selected publications (of 59 publications, total)

    1. Slifka, M.K., J. Whitmire, R. Antia, and R. Ahmed (1998). Humoral immunity due to long-lived plasma cells. Immunity  8:363-372.
    2. Slifka, M.K., Rodriguez, F., and J.L. Whitton (1999). Rapid on/off cycling of cytokine production by virus-specific CD8+ T cells. Nature 401:76-79.
    3. Slifka, M.K. and J. L. Whitton (2000). Antigen-specific regulation of T cell-mediated cytokine production. Immunity 12:451-457.
    4. Slifka, M.K. and J. L. Whitton (2001). Functional avidity maturation of CD8+ T cells results in greatly enhanced biological responsiveness without selection of higher affinity TcR. Nature Immunol. 2:711-717.
    5. Slifka, M.K., D. Homann, A. Tishon, R. Pagarigan, and M.B.A. Oldstone (2003). Measles virus infection results in suppression of both innate and adaptive immune responses to secondary bacterial infection.

      J. Clin. Invest.  11:805-810.

    1. Hammarlund, E., M.W. Lewis, S.G. Hansen, L.I. Strelow, J.A. Nelson, G.J. Sexton, J.M. Hanifin, M.K. Slifka (2003).  Duration of antiviral immunity following smallpox vaccination.  Nature Med. 9(9):1131-1137.
    2. Nikolich-Zugich, J., M.K. Slifka, and I. Messaoudi (2004). The many important facets of T-cell repertoire diversity. Nature Rev. Immunol.4:123-132.
    3. Raué, H.-P., J. Brien, E. Hammarlund, and M.K. Slifka (2004).  Activation of virus-specific memory T cells by LPS-induced IL-12 and IL-18. J. Immunol. 173(11):6873-6881.
    4. Beadling, C. and M.K. Slifka (2005).  Differential regulation of virus-specific CD8+ T cell effector functions elicited by peptide or innate cytokines. Blood. 105:1179-1186.
    5. Hammarlund, E., Lewis, M.W., Carter, S., Yoshihara, P., Hanifin, J., Hansen, S.G., Wong, S., Strelow, L.I., Amanna, I., and M.K. Slifka (2005).  Multiple diagnostic techniques identify previously immunized individuals with protective immunity against monkeypox. Nature Medicine 11(9):1005-1011.
    6. Amanna, I., M.K. Slifka, and S. Crotty (2006).  Immunity and immunological memory following smallpox vaccination. Immunol. Rev. 211:320-337.
    7. Beadling, C., and M.K. Slifka (2006). Quantitation of viable virus-specific T cells without a priori knowledge of fine epitope specificity.  Nature Medicine 12(10):1208-1212.
    8. Amanna, I., and M.K. Slifka  (2006).  Quantitation of rare memory B cell populations by two independent and complementary approaches. J Immunol Methods 317(1-2):175-185.
    9. Raué, H.-P. and M.K. Slifka (2007).  Pivotal Advance: CTLA-4 (CD152) expression does not inhibit T cell effector function during acute viral infection. J. Leuk. Biol. May;81(5):1176-8.
    10. Dasgupta, A. Hammarlund, E., Slifka, M.K., and K. Früh  (2007). Cowpoxvirus evades CTL killing and inhibits the intracellular transport of MHC class I molecules. J. Immunol. 178(3):1654-1661.
    11. Lewis, M.W., Hammarlund, E., Hanifin, J., M.K. Slifka (2007). Monkeypox without exanthem.                New England Journal of Medicine, 356;20:2112-2114.
    12. Koguchi, Y., Thauland, T.J., Slifka, M.K., and D.C. Parker (2007).  Preformed CD40 ligand exists in secretory lysosomes in effector and memory CD4+ T cells and is quickly expressed on the cell surface in an antigen specific manner.  Blood 110(7):2520-2527.
    13. Simpson, E., Hercher, M., Hammarlund, E., Slifka, M.K. and J.M. Hanifin (2007).  Cutaneous responses to vaccinia in individuals with previous smallpox vaccination.  Journal of the American Academy of Dermatology 57(3):442-444.
    14. Amanna, I.J., Carlson, N.E., and M.K. Slifka (2007). Duration of humoral immunity to common virus and vaccine antigens.  New England Journal of Medicine 357;19:1903-1915.
    15. Hammarlund, E., M.W. Lewis, J.M. Hanifin, E.L. Simpson, N.E. Carlson, and M.K. Slifka (2008).Traditional smallpox vaccination with reduced risk of inadvertent contact spread by administration of povidone iodine ointment. Vaccine, Jan 17;26(3):430-9.
    16. Dubois, M. and M.K. Slifka  (2008).  Retrospective analysis of monkeypox infection.                            Emerg Inf Dis, Apr;14(4):592-9.
    17.  Goldberg, T.L. Chapman, C.A., Cameron, K., Saj, T., Karesh, W., Wolfe, N., Wong, S.W., Dubois, M.D., and M.K. Slifka  (2008).  Serologic evidence for a novel poxvirus in endangered red colobus monkeys, Western Uganda. Emerg Inf Dis, May;14(5):801-3.
    18. Amanna, I.J., I. Messaoudi, and M.K. Slifka (2008). Protective immunity following vaccination: How is it defined? Hum Vaccin. 2008 Jul-Aug;4(4):316-9
    19. Walker, J.M., and M.K. Slifka (2008). The immunostimulatory power of acute viral infection.            Immunity, May;28(5):604-6.
    20. Hammarlund, E., Dasgupta, A., K. Pinilla, C. Norori, P., Früh, K., and M.k. Slifka (2008).  Monkeypox virus evades antiviral CD4+ and CD8+ T cell responses by blocking cognate T cell activation. PNAS Sep 23;105(38):14567-72.

 

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