- Ph.D. North Dakota State University
Building Address: 302 Connaway Hall
Phone Number: (573) 882-2597
My research is focused on immunity of the zoonotic, intracellular, bacterial pathogens Brucella and Francisella.
Research Project #1 Immunity and Immunopathology of Brucellosis.
Brucellosis remains one of the most common zoonotic infections world-wide with over 500,000 new human cases each year. In addition, Brucella causes disease and abortion in many of the agriculturally animals in the world resulting in wide-spread economic losses. While not life-threatening in humans, brucellosis can cause disease with relapses of undulating fever and lifelong complications, including arthritis, endocarditis, and possible neurological symptoms, despite antibiotic treatment. Osteoarticular complications are associated with prolonged illness in humans and are the most common localized manifestation of brucellosis occurring in up to 80% of cases. However, until recently the study of the immunology and pathology of focal complications of brucellosis has been hampered by the lack of relevant animal models. Recently we developed the first mouse model of Brucella-induced arthritis and showed that the cytokine IL-1 was critical for development of inflammation. Future work will investigate the role of IL-1-related pathways and other immunologic mediators of Brucella-induced inflammation.
Research Project #2. Immunity and Immunotherapy of Tularemia.
Francisella tularensis is a highly infectious, Gram-negative facultative intracellular bacterium that causes the zoonotic infection tularemia. F. tularensis subspecies tularensis (type A) and holarctica (type B) cause the majority of human cases, with subspecies tularensis being more virulent. Due to the high infectivity (10-50 microorganisms) and lethality (30-60% in untreated patients) of pulmonary type A F. tularensis infections, F. tularensis has been designated as a Category A Priority Pathogen by the CDC. In addition, F. tularensis has been weaponized by several countries, including the introduction of antibiotic resistance. As an alternative strategy to treat Francisella infections, we have investigated innate immune stimulation as a means of enhancing the efficacy of traditional antibiotic regimens. Stimulation of innate immunity can especially useful in situations where the etiologic agent of disease is unknown, since induced innate immune responses are often capable of providing protection against a broad range of organisms. In particular, we have found that immunotherapeutics that potentiate natural killer (NK) cells confer robust protection against pulmonary tularemia and other pulmonary bacterial infections. Current work is aimed at discovering new, and refining current immunotherapy strategies and also investigating pathways of protective immunity against tularemia that can be exploited via immunotherapy.
Rynda-Apple, A., Huarte, E., Maddaloni, M., Gallis, G., Skyberg, J.A., and Pascual, D.W., 2011. Active Immunization Using a Single Dose Immunotherapeutic Abates Established EAE via IL-10 and Regulatory T cells. Eur. J. Immunol. 41(2):313-23
Skyberg, J.A., Trunkle, T., Rollins, M.F., Huarte, E., Jutila, M.A., and Pascual, D.W. 2011. Murine and Bovine γδ T cells Enhance Innate Immunity Against Brucella abortus Infection. PloS One. 6:7e21978
Skyberg, J.A., Robison, A., Golden, S., Rollins, M.F., Huarte, E., Callis, G., Jutila, M.A., and Pascual, D.W. 2011 Apple Polyphenols Require T cells to Ameliorate Dextan Sulfate Sodium-Induced Colitis and Dampen Proinflammatory Cytokine Expression J. Leuk. Bio 90(6):1043-1054. Article highlighted in “Spotlight on Leading Edge Research,” picture featured on journal cover, and featured in a press release (http://www.sciencedaily.com/releases/2011/11/111130100455.htm)
Clapp. B, Skyberg, J.A., Yang, X., Trunkle, T., Walters, N., and Pascual, D.W. 2011. Protective Live Oral Brucellosis Vaccines Stimulate Th1 and Th17 Cell Responses. Infect. Immun. 79: 4165-4174
Huarte, E., Rynda-Apple, A., Riccardi, C., Skyberg, J.A., Golden, S., Rollins, M.F., Ramstead, A., Jackiw, L., Maddaloni, M. and Pascual, D.W. 2011. Tolerogen Stimulates Innate Mouse Interferon Producing Killer Dendritic Cells For Protection Against EAE. J. Autoimmun. 37(4):328-41
Skyberg, J.A.*, Holderness, J.H., Rollins, M.F., Marlenee, N., Schepetkin, I., Goodyear, A., Dow, S.W., Jutila, M.A., and Pascual, D.W. 2012. Nasal Acai Polysaccharides Potentiate Innate Immunity to Confer Protection Against Pulmonary Francisella tularensis and Burkholderia pseudomallei Infections. PloS Pathogens 8(3) e1002587 *Corresponding Author
Skyberg, J.A., Thornburg, T., Kochetkova, I., Layton, W., Callis, G., Riccardi, C., Becker, T., Rollins, M.F., Golden, S., and Pascual, D.W. 2012. IFN-γ-deficient MiceDevelop IL-1-Dependent Cutaneous and Musculoskeletal Inflammation During Experimental Brucellosis. J. Leuk Bio. 92(2):375-87
Yang, X., Skyberg, J.A., Cao, L., Thornburg, T., Clapp, B., and Pascual, D.W. 2012. Progress in Brucella vaccine development. Front. Biol. (In press).
Skyberg, J.A. 2013. Immunotherapeutics for Biodefense: Tularemia and Beyond. Virulence. (Invited Review in Preparation).