Faculty Research Interests
Jennifer F Moffat, PhD
- Associate Professor of Microbiology and Immunology
Research Programs and Affiliations
- Biomedical Sciences Program
- Microbiology and Immunology
Education & Fellowships
- Postdoctoral Fellow: Stanford University, 1999
- PhD: Stanford University, 1994
Varicella zoster pathogenesis.
Diseases & Conditions Treated
- American Society for Microbiology (ASM)
Link to PubMed (Opens new window. Close the PubMed window to return to this page.)
Most people in the U.S. have had chicken pox, caused by the varicella zoster virus (VZV), or have received the vaccine. This virus remains latent in the body for life, and can reactivate as the disease called shingles. Learning how VZV interacts with human cells is the major goal of our research, and we hope to use this knowledge to develop new drug treatments and to improve the vaccine.
Current work in my lab is focused on the cell functions that are required for VZV replication. Specifically, we are looking at how VZV dysregulates cell cycle proteins, what effects VZV has on cellular DNA synthesis, and how VZV impacts cell-signaling kinase cascades. To study these aspects of virology and cell biology, we have used chemical inhibitors of cellular kinases to understand what enzymes are needed for VZV to grow. We found that a cell cycle kinase inhibitor, roscovitine, is highly potent against VZV replication, viral gene transcription, and protein expression. Other compounds that target the cell are being studied for their antiviral properties.
Other tools that we use to study VZV are virus mutants, a mouse model of virus replication, and skin organ culture. Using human skin, either grown in culture or implanted into SCID mice, we have identified genes that are necessary for this virus to replicate in skin. Since chicken pox and shingles are infamous for itchy, painful skin lesions, this is a very important system for studying VZV. Creating mutant viruses to study in the skin model has been slow, but molecular techniques exist, and new ones are being developed, to analyze the contribution of individual VZV genes to pathogenesis.
Moffat, Jennifer F., Leigh Zerboni, Paul R. Kinchington, Charles Grose, Hideto Kaneshima, and Ann M. Arvin. 1998. Attenuation of the vaccine Oka strain of varicella-zoster virus and the role of glycoprotein C in alphaherpesvirus virulence demonstrated in the SCID-hu mouse. Journal of Virology, 72:965-974.
Moffat, Jennifer F., Leigh Zerboni, Marvin H. Sommer, Thomas C. Heineman, Jeffrey, I. Cohen, Hideto Kaneshima, and Ann M. Arvin. 1998. The ORF47 and ORF66 putative protein kinases of varicella-zoster virus determine tropism for human T cells and skin in the SCID-hu mouse. Proceedings of the National Academy of Sciences, USA, 95:11969-11974.
Moffat, Jennifer F. and Ann M. Arvin. 1999. Varicella-zoster virus infection of T cells and skin in the SCID-hu mouse model. In Handbook of Animal Models of Infection, pp. 973-979. Academic Press, London.
Santos, Richard A., Christopher C. Hatfield, Benjamin P. Faga, Jorge A. Padilla, Nancy L. Cole, Jennifer F. Moffat, Ann M. Arvin, William T. Ruyechan, John Hay, and Charles Grose. 2000. Varicella-zoster virus gE escape mutant VZV-MSP: a novel genotype with an accelerated cell-to-cell spread phenotype in both infected cell cultures and SCID-hu mice. Virology, 275:306-317.
Moffat, Jennifer F., Hideki Ito, Marvin Sommer, Shannon Taylor and Ann M. Arvin. 2002. Glycoprotein I of varicella zoster virus is required for viral replication in skin and T cells. Journal of Virology, 76:8468-8471.
Besser J. Sommer MH. Zerboni L. Bagowski CP. Ito H. Moffat J. Ku CC. Arvin AM. 2003. Differentiation of varicella-zoster virus ORF47 protein kinase and IE62 protein binding domains and their contributions to replication in human skin xenografts in the SCID-hu mouse. Journal of Virology, 77:5964-74.
Taylor, Shannon L, Paul R. Kinchington, Andrew Brooks, and Jennifer F. Moffat. 2003. The cyclin-dependent kinase inhibitor roscovitine prevents varicella zoster virus replication and DNA synthesis. Journal of Virology, 78:2853-2862.
Moffat, Jennifer F., Stacey A. Leisenfelder, Michelle A. McMichael, and Shannon L. Taylor. 2004. Viral and cellular kinases are potential antiviral targets and have a central role in varicella zoster virus pathogenesis. Biochimica et Biophysica Acta, in press.