- 2011 - Melville A. Hare Award for Distinction in Research
Kendra began chemistry research as a high school student in the University of Rochester Laboratory for Laser Energetics Summer High School Research Program, and as a result of that project, was a regional semi-finalist in the Siemens-Westinghouse Science Competition in 1999. She graduated from the Massachusetts Institute of Technology in 2005 with a Bachelor of Science degree in chemistry. Her undergraduate research included natural product discovery and green chemistry alternatives to reduce toxic compound use. While at MIT she received the Hypercube Scholar Award and EPA P3 Student Design Competition Team Awards.
Kendra spent several summers during college working as a summer student at the University of Rochester School of Medicine and Dentistry, and in September 2005 began her graduate studies in the Pathways of Human Disease program. She received the Irving Spar Fellowship Award in 2005. She entered the PhD program in Microbiology and Immunology in June 2006 and joined the laboratory of Dr. Toru Takimoto where she began research on the influenza nuclear export and assembly process, as well as studies of the polymerase components and mutations that contribute to adaptation of avian influenza viruses to the mammalian host.
During her studies at the University of Rochester, Kendra was a teaching assistant for the Microbiology Laboratory course, co-President and subsequently President of the Graduate Student Society, and a member of the University Council on Environmental Sustainability. She received travel awards to present her research at the Immunobiology and Pathogenesis of Influenza Infection 2008 Meeting and the 28th Annual Meeting of the American Society for Virology in 2009. She also attended the NIH/NIAID CEIRS Annual Meetings in 2009 and 2010, and presented her work at Options for the Control of Influenza VI and VII in 2007 and 2010.
Influenza A viruses cause seasonal epidemics and occasional pandemics in humans. All 16 hemagglutinin and 9 neuraminidase subtypes have been detected in wild waterfowl, but only limited strains can infect humans. The emergence of new influenza strains in humans can lead to pandemics, and this process may occur through two distinct mechanisms: reassortment of viral genes, or direct mutation. The mutations required for host adaptation are found in multiple viral genes, including the hemagglutinin and the heterotrimeric RNA-dependent RNA polymerase comprised of PA, PB1, and PB2.
Previous studies have revealed a single mutation in PB2, E627K, significantly enhances polymerase activity and pathogenicity in the mammalian host. However, some highly pathogenic H5N1 avian influenza viruses lack PB2 627K, but cause severe disease in mammals. The mechanism of adaptation of these highly pathogenic PB2 627E viruses is unknown. We hypothesized that additional, unidentified changes in the polymerase complex can contribute to enhanced polymerase activity and pathogenicity of avian influenza strains in mammalian species.
Through our studies, which utilized techniques including influenza minigenome polymerase activity assays, influenza virus rescue, and viral characterization, we have identified mutations in the influenza polymerase genes PB2 and PA that enhance mammalian adaptation of avian influenza viruses. The PB2 residue 271A and the PA residues 85I, 186G, and 336M enhance polymerase activity in mammalian cells, as well as viral growth in vitro and/or pathogenicity in vivo, suggesting the contribution of these amino acids to host adaptation and pathogenicity. Knowledge of the adaptive markers required for mammalian and human adaptation of avian polymerase genes will help direct surveillance efforts for isolation of potential threats to human health. Future studies to determine the mechanism of these mutations in polymerase function may help develop new therapeutic agents against influenza virus.
- Bussey, K. A., T. L. Bousse, E. A. Desmet, B. Kim, and T. Takimoto. 2010. PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells. J. Virol. 84: 4395-4406
Bussey, K. A., E. A. Desmet, J. Mattiacio, A. Hamilton, B. Bradel-Tretheway, H. E. Bussey, B. Kim. S. Dewhurst, and T. Takimoto. Submitted. PA residues in the 2009 H1N1 pandemic influenza virus enhance avian virus polymerase activity in mammalian hosts.