Dr. Earl Brown
B.Sc. (Guelph), Ph.D. (McMaster)
Roger Guindon Hall, Rm. 4109
Phone: 562-5800 ext. 8310
Focus: Molecular-genetic analysis of RNA viruses with segmented genomes.
Long range goals
- Determination of the genetic basis for disease production
- Prediction of viral biology from genetic sequence
- Develop therapeutically active viruses for the treatment of cancer and chronic disease.
Pathogenesis is being studied with molecular and genetic approaches using the influenza virus, mumps virus, vesicular stomatitis virus (VSV), hepatitis C virus, SARS coronvirus and reovirus systems. Studies are aimed at understanding viral replication and pathogenesis so that antiviral therapies can be developed. A major focus is the analysis of viral evolution with particular reference to virulence and virus-host interaction. Evolution of hepatitis C virus and influenza virus is providing insights into the characterization of biologically meaningful genetic changes. Mutations have been identified in individual genes that control virulence in mice. Current work is aimed at identifying the mechanism of action of these mutations using genetic reassortants and molecular techniques.
- Influenza evolution and genetic basis for virulence and host switching are being analyzed in multiple animal models
- Genetic variants of VSV and reovirus are being derived for cancer treatment.
- Patterns of evolution are being mapped for Torque Teno virus (TTV) and hepatitis C viruses
Using the reovirus system, genome replication and assembly are studied as well as the biology of the mu2 protein. The mu2 protein controls the rate of formation of viral inclusion bodies and controls the resistance of virus to inhibition by specific host defenses such as interferon. A current focus is the characterization of the modification of the host cell by reovirus during infection.
- John P. Cortens, Darwyn Kobasa, John Wilkins, and Earl G. Brown. 2010. Quantitative Proteomic Analyses of Influenza virus-Infected Cultured Human Lung Cells (1.74 MB). Journal of Virology.
- Jihui Ping, Samar K. Dankar, Nicole E. Forbes, Liya Keleta, Yan Zhou, Shaun Tyler, and Earl G. Brown. 2010. PB2 and HA Mutations are Major Determinants of Host Range and Virulence in Mouse-Adapted Influenza A Virus (1007 KB). Journal of Virology.
- Bauer CM, Zavitz CC, Lambert KN, Brown EG, Mossman KL, Stampfli MR. 2010. Treating viral exacerbations of copd with steroids: Lessons learned from animal models of cigarette smoke exposure and influenza a virus infection. Am J Respir Crit Care Med;181:A1016-.
- Bauer CM, Zavitz CC, Lambert KN, Brown EG, Mossman KL, Stampfli MR. 2010. Targeting peroxisome proliferator activated receptor-gamma may be important for attenuating exacerbated inflammatory responses to influenza a virus in smoke-exposed mice. Am J Respir Crit Care Med;181:A3824-.
- Cherrie-Lee Small, Christopher R. Shaler, Sarah McCormick, Mangalakumari Jeyanathan, Daniela Damjanovic, Earl G. Brown, Petra Arck, Manel Jordana, Charu Kaushic, Ali Ashkar & Zhou Xing. 2010. Influenza infection leads to increased susceptibility to subsequent bacterial superinfection by impairing NK cell responses in the lung (963 KB). Journal of Immunology, 2010 Feb 15;184(4):2048-56.
- Anwar M. Hashem, Anathea S. Flaman, Aaron Farnsworth, Earl G. Brown, Gary Van Domselaar, Runtao He, Xuguang Li (2009) Aurintricarboxylic Acid is a Potent Inhibitor of Influenza A and B Virus Neuraminidases (1.37 MB). PLoS ONE.
- Yan L. Cong, Juan Pu, Qin F. Liu, Guo Z. Zhang, Wei X. Fan, Earl G. Brown 3, Jin H. Liu. J. Gen. Virology 2007. Antigenic and genetic characterization of H9N2 Swine Influenza Viruses in China (172 KB).
- Maziar Divangahi, Tony Yang, Kapilan Kugathasan, Sarah McCormick, Shunsuke Takenaka, Gordon Gaschler, 1 Ali Ashkar, Martin Stampfli, Jack Gauldie, Jonathan Bramson, Toshiyuki Takai, Earl Brown, Wayne M. Yokoyama, Naoko Aoki and Zhou Xing. Critical Negative Regulation of Type 1 T Cell Immunity and Immunopathology by Signaling Adaptor DAP12 during Intracellular Infection (1.03 KB). 2007. Journal of Immunology
- Nielson K, Yu WL, Mackenzie R, Tanha J, Li S, Dubuc G, Brown EG, Keleta L, Pasick J, Lin M, Nadin Davis SA, Elmgren C (2007) Prototype Single Step Lateral Flow Technology for Detection of Avian Influenza Virus and Chicken Antibody to Avian Influenza Virus (129 KB). Journal of Immunoassay and Immunochemistry.
- Clinton S. Robbins, Carla M.T. Bauer, Neda Vujicic, Gordon J. Gaschler, Brian D. Lichty, Earl G. Brown and Martin R. Stämpfli. (2006) Cigarette Smoke Impacts Immune Inflammatory Responses to Influenza in Mice (1002 KB). American Journal of Respiratory and Critical Care Medicine 174(12):1342-51
- Aida Ibricevic, Andrew Pekosz, Michael J. Walter, Celeste Newby, John T. Battaile, Earl G. Brown, Michael J. Holtzman, and Steven L. Brody. 2006 Influenza virus receptor specificity and cell tropism in mouse and human airway epithelial cells (1.30 MB). J Virology 2006 80:7469-80.
- Yu-Wen Hu, Moslih I. Al-Moslih, Mahmoud Talib Al Ali, Shabnam Rahimi Khameneh, Heather Perkins, Francisco Diaz-Mitoma, Jean Nicholas Roy, Samra Uzicanin, Earl G. Brown (2005). Molecular detection method for all known genotypes of TT virus (TTV) and TTV like viruses (TTLVs) in thalassemia patients and healthy individuals (248 KB). Journal Clinical Microbiology 43, 3747-3754.
- Hu YW, Rocheleau L, Larke B, Chui L, Lee B, Ma M, Liu S, Omlin T, Pelchat M, Brown EG. Immunoglobulin mimicry by Hepatitis C Virus envelope protein E2 (922 KB). Virology. 2005 Feb 20; 332(2):538-49.
- David F. Stojdl, Brian D. Lichty, Benjamin R. tenOever, Jennifer M. Paterson, Anthony T. Power, Shane Knowles, Ricardo Marius, Jennifer Reynard, Laurent Poliquin, Harold Atkins, Earl G. Brown , Russell K. Durbin, Joan E. Durbin, John Hiscott, and John C. Bell (2003) VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents (579 KB). Cancer Cell, Vol. 4, 263-275.
- Brown, E.G. and J. Tetro. (2003). Comparative analysis of the SARS coronavirus genome: a good start to a long journey. (Commentary). The Lancet 361, 1756-7.
- Brown, E.G. , H. Liu, L. Chang Kit, S. Baird and M. Nesrallah. (2001). Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: identification of functional themes (260 KB). Proceedings of the National Academy of Sciences 98, 6883-6888.
- Stojdl, D.F., N. Abraham, S. Knowles, R. Marius, A. Brasye, E.G. Brown, N. Sonenberg and J.C. Bell. (2000). The murine double stranded RNA dependent protein kinase, PKR is required for resistance to VSV. J. Virology 74, 9580-5.
- Brown, E.G. and Bailly, J.E. (1999). Genetic analysis of mouse-adapted influenza A virus identifies roles for the NA, PB1 and PB2 genes in virulence (371 KB). Virus Research 61, 63-76.
- Brown, E.G. , K. Dimock and K.E. Wright. (1996). The Urabe AM9 mumps vaccine is a mixture of viruses differing at amino acid 335 of the HN gene with one form associated with disease. J. Infectious Diseases 174, 619-22.
- Zou, S. and E.G. Brown. 1996. Stable expression of the reovirus mu2 protein in mouse L cells complements the growth of a reovirus ts mutant with a defect in its M1 gene. Virology 217, 42-48.