239B Veterinary Science 1971 Commonwealth Avenue University of Minnesota
St. Paul, MN 55108
Education
B.S., University of Notre Dame Ph.D., Ohio State University Post-Doctoral, University of Texas Medical School, Houston
Research Interests The Murtaugh laboratory seeks a comprehensive understanding of porcine immune responses to infectious pathogens, particularly at mucosal surfaces. We have established an oral immunization model for the induction of mucosal immune responses in swine and have explored the role of cytokines in mediating mucosal adjuvanticity. Cholera toxin is a potent oral adjuvant for both local and distant mucosal, and for systemic responses, and elicits both antibody and cell-mediated immunity. These effects are associated with induction of IL-1, IL-12 and costimulatory molecule expression on macrophages. Currently, we are using gene discovery approaches and Salmonella as a model pathogen to identify the complete catalog of molecular responses to intestinal infection. The overall goal of this investigation is to elucidate the initiating molecular and cellular responses in the small intestine that are crucial in determining the outcome of enteric infection and the extent to which they are modified by opioid drugs.
A second programmatic interest is to understand the immunological interaction of persistent viruses with pigs. Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-sense, single-stranded RNA virus that infects macrophages without provoking a notable innate response. The infection is prolonged, and the immune response appears to be delayed and ineffective. The resulting immunity is robust against re-infection with the same virus but less effective against other strains. The mechanisms of protective immunity are unknown, and means of enhancing primary responses have been difficult to discern. The virus recombines at a high rate to produce chimeric genomes and novel subgenomic RNAs. Understanding the biochemistry and molecular biology of recombination will provide insights into fundamental mechanisms of viral evolution and radiation that may be related to the appearance of novel diseases in swine and other species. We also are studying the immune response to porcine circovirus type 2 (PCV2), another virus of swine that is characterized by prolonged infection. Its small genome, encoding about 3 proteins, is amenable to global dissection and characterization of the complete immune response to a viral pathogen. The results of our research will help the development of novel approaches for treatment of enteric illness and disease, and also will help to identify new pharmacological and immunologic targets capable of enhancing the efficacy of drugs and vaccines. We also are involved in collaborative studies to study the patterns of cytokine and cytotoxic T cell effector molecule expression associated with engraftment and rejection of islet xenotransplants between pigs and monkeys.
Selected Publications (For a comprehensive list of Dr. Murtaugh's recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Hering, B.J., M. Wijkstrom, M.L. Graham, M. Hardstedt, T.C. Aasheim, T. Jie, J.D. Ansite, M. Nakano, J. Cheng, W. Li, K. Moran, U. Christians, C. Finnegan, D.E. Sutherland, P. Bansal-Pakala, M.P. Murtaugh, N. Kirchhof, and H.J. Schuurman. 2005. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates without anti-Gal antibody manipulation. Nature Med. 12:301-303.
Hyland, K.A., L. Kohrt, L. Vulchanova, and M.P. Murtaugh. 2006. Mucosal innate immune response to intragastric infection by Salmonella enterica serovar Choleraesuis. Mol. Immunol. 43:1890-1899.
Dvorak, C.M.T., G.N. Hirsch, K.A. Hyland, J.A. Hendrickson, B.S. Thompson, M.S. Rutherford, and M.P. Murtaugh. 2006. Genomic dissection of mucosal immunobiology in the porcine small intestine. Physiol. Genom. 28:5-14.
Johnson, C.R., W. Yu, and M.P. Murtaugh. 2007. Cross-reactive antibody responses to nsp1 and nsp2 of Porcine reproductive and respiratory syndrome virus. J. Gen. Virol. 88:1184-1195.
Dvorak, C.M.T., M.A. Hardstedt, H. Xie, M. Wang, K.K. Papas, B.J. Hering M.P. Murtaugh, and S.C. Fahrenkrug. 2007. Transcriptional profiling of stress response in cultured porcine islets. Biochem. Biophys. Res. Commun. 357:118-125.
Mulupuri, P., J.J. Zimmerman, J. Hermann, C.R. Johnson, J.P. Cano, W. Yu, S.A. Dee, and M.P. Murtaugh. 2008. Antigen-specific B-cell responses to Porcine reproductive and respiratory syndrome virus infection. J. Virol. 82:in press.
Current Funding "Molecular Mechanisms of Mucosal Immunity," USDA-NRICGP.
"Integrated control and elimination of PRRSV in the US," USDA-NRICGP.
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