 | Dr. Scott NapperEmerging Diseases & Microbial Virulence
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Biography
Dr. Scott Napper holds a joint position at the University of Saskatchewan as an Associate Professor of Biochemistry as well as Senior Scientist and Program Manager of Emerging Diseases at the Vaccine and Infectious Disease Organization (VIDO). A protein biochemist by training, his research interests are based in the application of structure activity investigations within the context of infection and immunity. Specifically, his currently active research programs include structural modifications of host defense peptides for immunotherapeutic applications (vaccine adjuvants and antimicrobials), vaccine development for Johne's Disease and development of a PrPSc specific vaccine for prion diseases. Dr. Napper's work in development of a prion vaccine is centralized in the optimization of epitopes to maximize immunogenicity, while maintaining PrPSc specificity, as well as the application and optimization of various parameters of vaccine formulation and delivery. Outside of the lab Scott has a strong interest in Science Education and works actively with the Secondary Education System to help translate higher level science and mentorship to undergraduate and high school students. In the past five years, Scott has twice been awarded the University of Saskatchewan Teaching Excellence Award.
Responsibilities
♦ Program Manager: Emerging Diseases and Microbial Virulence
♦ Project Leader: Prion Vaccine Development; Johne's Disease; Kinome analysis
♦ Associate Professor: Department of Biochemistry, University of Saskatchewan
♦ Associate Member: School of Public Health
Education:
♦ University of Saskatchewan, Department of Biochemistry, Ph.D. 1999
Major Accomplishments:
♦ Establishment of a novel system to screen interactions of Toll-like Receptor 9 with nucleic acids
♦ Establishment of a system for optimization of host-defense peptides to minimize activation of bacterial defensive responses
Current Research Interests:
1) Prion diseases in a variety of mammalian species are characterized by the conversion of the normal host protein (PrPC) to an abnormal infectious form (PrPSc). A research team led by Dr. Neil Cashman has identified and characterized a surface-exposed antibody-binding site which is present on PrPSc but not PrPC. This site is conserved among PrPSc of a wide variety of mammalian species, thus making it an excellent universal vaccine target for prevention and therapy of diseases such as BSE and CWD. The primary objective of this proposal is to develop vaccine formulations and vaccination protocols f which generate sustained levels of antibodies that react specifically with PrPSc but not PrPC.
2) Johne's Disease: Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, a chronic inflammatory disorder of the gastrointestinal tract of ruminants . Johne's disease is of considerable economic importance in dairy cattle as it is responsible for the highest average production losses among five production-limiting diseases. There is additional growing concern that MAP may be a causative, or contributing, factor to Crohn's Disease in humans. The potential zoonotic threat, and realized economic impact, of Johne's Disease has energized efforts for development of an effective disease management strategies. However, the limited success of traditional approaches to vaccine design for Johne's disease indicates that greater understanding of the biology and virulence mechanisms of MAP is required to adopt a more strategic approach to vaccine design. Specifically, an understanding of the mechanisms by which MAP subverts host immune responses could form the basis for development of vaccine formulations and strategies.VIDO recently instigated a Johne's Disease Program focused on development of an effective vaccine and/or therapeutic. Since its inception our group has developed three key platforms to be applied to the current proposal: 1) Development of a novel technology for characterization of global kinase activity (the kinome) in bovine cells, 2) Identification of immunotherapy treatments that clear MAP from infected monocytes and 3) Creation of a stable bovine gut loops for characterization of acute and chronic host responses to MAP infection. These tools will collectively enable us to achieve a greater understanding of the virulence mechanisms of MAP. We believe that understanding the mechanisms by which the bacterium subverts host immune responses will form the basis for development of an effective vaccine and/or therapeutic.
3) Kinome Analysis Phosphorylation represents the pivotal mechanism for regulation of cellular processes, and kinases are one of the most biologically important classes of enzymes . The regulatory roles of kinases in cellular pathways and disease, as well as their conserved catalytic cleft, make them attractive targets for drug therapy. The therapeutic and biological importance of kinases has prompted the development of novel strategies for quantification of their activity. Sites of protein phosphorylation and their subsequent biological consequences are often conserved; therefore, it should be possible to predict the sequence contexts of phosphorylation events in proteins of other species on the basis of genomic information. To demonstrate the feasibility of this approach, we selected a set of phosphorylation events that represent the major signal transduction pathways, with an emphasis on pathways and processes relating to innate immunity. We then created a bovine peptide array for kinome analysis and have successfully applied this technology to several diseases. Species-specific arrays for other non-traditional laboratory species are being pursued.
