Faculty Summaries
Luis J Sigal, DVM, PhD
Luis J Sigal, DVM, PhD
Professor
  • Adjunct Assistant Professor of Microbiology, University of Pennsylvania School of Medicine
  • Adjunct Associate Professor, Microbiology & Immunology, Thomas Jefferson University
Luis.Sigal@fccc.edu
Office Phone: 215-728-7061
Lab Phone: 215-728-7065,7067,7020
Fax: 215-728-2412
Office: W260
Viral Immunology

The overall goals of my laboratory are to determine how vaccines induce the immune system; to identify the mechanisms that contribute to vaccine-mediated protection from disease; and to understand how the interplay of viral gene products with the innate and adaptive immune systems of the host determine susceptibility or resistance to viral disease in immune and non-immune hosts. The importance of these goals in general is that we still do not completely understand how anti-viral vaccines and the immune system protect from viral disease. Hence, our work should yield important insights to develop new anti-viral vaccines and treatments. The role of our work within a Cancer Center is that there is a strong interest in developing anti-cancer vaccines. In our mind, the immune system mainly evolved to combat pathogenic microorganisms but could be coerced to combat cancer if we learn how to manipulate it. Thus, learning how the immune system is best stimulated to eliminate viruses should provide essential insights on how to force it to effectively attack cancer cells. Also, viruses can be used as vectors for anti-viral vaccines. Moreover, many cancers are known or thought to be caused by viruses.

Our work currently focuses on two major research programs. 1) We are studying antigen presentation during viral infections. 2) We are studying viral pathogenesis in a natural host using as a model the laboratory mouse specific pathogen Orthopoxvirus (OPV) ectromelia virus (ECTV), the causative agent of mousepox (the murine parallel of human smallpox).

Description of research projects
Selected Publications
  1. Rubio, D., Xu, R.-H., Remakus, S., Krouse, T.E., Truckenmiller, M.E., Thapa, R., Balachandran, S., Alcami, A., Norbury, C.C., Sigal, L.J. Cross-talk between the Type I interferon and Nuclear Factor Kappa B pathways rescues resistance to a viral disease. Cell Host Microbe 2013;13:701-10. PubMed
  2. Remakus S, Rubio D, Lev A, Ma X, Fang M, Xu R-H, Sigal, LJ. Memory CD8 T cells can outsource IFN-γ production but not cytolytic killing for anti-viral protection. Cell Host Microbe 2013;13:546-57. PubMed
  3. Ma X, Xu R-H, Roscoe F, Whitbeck JC, Eisenberg RJ, Cohen GH, Sigal LJ. The mature virion of a pathogenic orthopoxvirus is important for late spread in vivo serving as a target for delayed therapy. J Virol. 2013;87:7046-53. PubMed
  4. Roscoe F, Xu R-H, Sigal LJ. Characterization of Ectromelia virus deficient in EVM036, the homolog of Vaccinia virus F13L, and its application for the rapid generation of recombinant viruses. J Virol. 2012;86:13501-7. PubMed
  5. Remakus S, Rubio D, Ma X, Sette A, Sigal LJ. Memory CD8 T cells specific for a single immmunodominant or subdominant determinant induced by peptide-dendritic cell immunization protect from an acute lethal viral disease. J Virol. 2012;86:9748-59. PubMed
  6. Fang M, Siciliano NA, Hersperger AR, Roscoe F, Hu A, Ma X, Shamsedeen AR, Eisenlohr LC, Sigal LJ. Perforin-dependent CD4+ T-cell cytotoxicity contributes to control a murine poxvirus infection. Proc Natl Acad Sci USA. 2012;109:9983-8. PubMed
  7. Xu R-H, Rubio D, Roscoe F, Krouse TE, Truckenmiller ME, Norbury CC, Hudson PN, Damon IK, Alcami A, Sigal LJ. Antibody inhibition of a viral type 1 interferon decoy receptor cures a viral disease by restoring interferon signaling in the liver. PLoS Pathogens. 2012;8:e1002475. PubMed
  8. Remakus S, Sigal LJ. Interferon gamma and perforin control the strength, but not the hierarchy, of immunodominance of an anti-viral CD8+ T cell response. J Virol. 2011;85:12578-84. PubMed
  9. Fang M, Orr MT, Spee P, Egebjerg T, Lanier LL, Sigal LJ. CD94 is essential for NK cell-mediated resistance to a lethal viral disease. Immunity 2011;34:579-89. PubMed
  10. Orr MT, Wu J, Fang M, Sigal LJ, Spee P, Egebjerg T, Dissen E, Fossum S, Phillips JH, Lanier LL. Development and function of CD94-deficient natural killer cells. PLoS ONE 2010;5:e15184. PubMed
  11. Fang M, Roscoe F, Sigal LJ. Age-dependent susceptibility to a viral disease due to decreased natural killer cell numbers and trafficking. J Exp Med 2010;207:2369-81. PubMed
  12. Fang M, Sigal LJ. Studying NK cell responses to ectromelia virus infections in mice. In: Natural Killer Cell Protocols, Methods in Molecular Biology Series (Campbell KS, ed), 2nd Edition, Chapter 28, vol. 612, pp. 411-428. Humana Press, 2010.
  13. Xu R-H, Remakus S, Ma X, Roscoe F, Sigal LJ. Direct presentation is sufficient for an efficient anti-viral CD8+ T cell response. PLoS Pathog 2010;6:e1000768. PubMed
  14. Ma X, Serna A, Xu R-H, Sigal LJ. The amino acids sequences flanking an antigenic determinant can strongly affect MHC class I cross-presentation without altering direct-presentation. J Immunol 2009;182(8):4601-07. PubMed
  15. Xu R-H, Cohen M, Tang Y, Lazear E, Whitbeck JC, Eisenberg RJ, Cohen GH, Sigal LJ. The Orthopoxvirus type I IFN binding protein is essential for virulence and an effective target for vaccination in a natural host. J Exp Med 2008;205:981-92. PubMed
All publications