Karen Mossman, PhD

Associate Professor
Pathology and Molecular Medicine

Division: Molecular Medicine

Associate Member, Biochemistry and Biomedical Sciences

McMaster University
5026 Michael DeGroote Centre for Learning & Discovery
905-525-9140 ext. 23542
mossk@mcmaster.ca

Assistant: Debra Vanderaar

Faculty Biography

Education and Professional Standing

PhD Biochemistry, University of Alberta 1997
HBSc Molecular Biology and Genetics, University of Guelph 1992

Interests

Research Focus

The focus of our research is to understand how viruses evade host immune defenses. When a virus infects a host, the host mounts an impressive immune response aimed at preventing the virus from multiplying and spreading. Viruses have evolved strategies to block this response in order to ensure their survival. Probably the most important aspect of the host immune response to virus infection is the production of an immune modulator called interferon. Interferon has a great impact on host defense mechanisms and as a result viruses have evolved multiple strategies to overcome its activities. We are currently studying the mechanisms of interferon inhibition and the countermeasures taken by different viruses.

These studies have led us to developing viruses for use in gene therapy and cancer therapy. The virus that we focus on is herpes simplex virus type 1 (HSV-1) which is a human pathogen that causes cold sores. We have found that by disabling the virus through removal of particular genes, the virus can grow in cancer cells and kill these cells while having no effect on healthy cells. Such viruses, called "oncolytic viruses" are currently being tested as a novel approach to cancer therapy in the hopes of eliminating tumors without the toxic side effects associated with many current treatments. HSV-1 is also being studied as a tool for gene therapy, since it is easy to manipulate, it can be targeted to specific tissues and it can house several therapeutic genes in a single vector. Thus, overall, our goal is to understand how viruses and their hosts interact with each other so that we can use viruses as tools for the treatment of multiple diseases.

Academic Interests

Dr. Mossman is involved in teaching within the Faculty of Health Sciences within the following programs:

Bachelor of Health Sciences Undergraduate Program, HTH SCI 3K03: Introductory Virology
Medical Sciences Graduate Program, MS763: Medical Virology

Team Members

Technicians: Susan Collins, Derek Cummings

Research Assistant: Rebecca Rodrigues

PhD Students: Carla Bauer (Co-Supervisor), Tracy Chew, Patrick Paladino, Paul Sobol, Katie Taylor

MSc Students: Breanne Cuddington, Amanda Dyer

Post-Doctoral Fellows: Stephanie Dewitte-Orr, Jeffrey Hummel, Raheleh Masoudi

Selected Publications

Paladino, P., & Mossman, K.L. Mechanisms employed by HSV-1 to inhibit the interferon response. Journal of Interferon and Cytokine Research (In press).

Sobol, P.T., Hummel, J., Rodrigues, R., and Mossman, K.L. (2009). PML plays a predictive role in tumor killing by interferon-sensitive viruses. Gene Therapy May 28 [Epub ahead of print].

Noyce, R., Collins, S., and Mossman, K.L. (2009). Characterization of the interferon regulatory factor 3 following virus particle entry. Journal of Virology, 83(9), 4013-22.

Chew, T., Noyce, R., Collins, S.E., Hancock, M.H. and K. L. Mossman. (2009) Characterization of the interferon regulatory factor 3-mediated antiviral response in a cell line deficient for IFN production. Molecular Immunology 46(3), 393-9.

Ashkar, A. A., Mossman, K. L., Coombes, B. K., Gyles, C. L., and Randy Mackenzie. (2008) FimH adhesin of type 1 fimbriae is a potent inducer of innate antimicrobial responses which requires TLR4 and type 1 interferon signaling. PLoS Pathogens 4(12), e1000233.

Mossman, K.L, Lauzon, N.M., Gyles, C.L., Lichty, B., Mackenzie, R., Mian, F., Gill, N., and A. A. Ashkar. (2008) Cutting Edge: FimH adhesin of type 1 fimbriae is a novel TLR4 ligand. Journal of Immunology 181(10), 6702-6706.

Bauer, C.M., DeWitte-Orr, S.J., Hornby, K.R., Zavitz, C.C., Lichty, B.D., Stämpfli, M.R., and K. L. Mossman(2008) Cigarette smoke suppresses innate antiviral immunity in human lung fibroblast and epithelial cells. Journal of Interferon and Cytokine Research, 28(3), 167-79.

Paladino, P., Cummings, D., Noyce, R. and K. L. Mossman. (2006) The interferon-independent response to virus particle entry provides a first line of antiviral defense that is independent of TLRs and RIG-I. Journal of Immunology, 177(11), 8008-16.

Paul T. Sobol and K. L. Mossman. (2006) ICP0 prevents RNase L-Independent rRNA cleavage in herpes simplex virus type 1-infected cells. Journal of Virology 80(1), 218-225.

Ryan S. Noyce, Susan E. Collins and K. L. Mossman. (2006) Identification of a novel pathway essential for the immediate-early, interferon-independent antiviral response to enveloped virions. Journal of Virology 80(1), 226-235.

Hummel, J. L., Safroneeva, E. and K. L. Mossman. (2005) The role of ICP0-null HSV-1 and interferon signaling defects in the effective treatment of breast adenocarcinoma. Molecular Therapy 12(6), 1101-10.

K. L. Mossman and A. A. Ashkar. (2005) Herpesviruses and the innate immune response. Viral Immunology 18, 267-81.

Lin, R., Noyce, R., Collins, S., Everett, R. and K. L. Mossman. (2004) The herpes simplex virus ICP0 RING finger domain inhibits IRF3- and IRF7-mediated activation of interferon-stimulated genes. Journal of Virology 78, 1675-1684.

Collins, S., R. Noyce and K. L. Mossman. (2004) The innate cellular response to virus particle entry requires IRF3 but not virus replication. Journal of Virology 78(4), 1706-1717.