The goal of this application is to establish the Pacific Northwest Regional Center of Excellence (PNWRCE) in NIAID Region X. The two inter-related but distinct PNWRCE themes that we have selected reflect not only the scientific strengths at our institutions but also the unmet needs that we perceive are absent in the NIAID biodefense and emerging disease program. The first theme "Identification of Age-Related Defects in the Immune System to Develop Vaccines and Supplemental Therapies" will include two projects. The overall goal of these projects is to develop new vaccines and immune supplemental therapies for immune vulnerable populations such as aged individuals. The first project a P01 will investigate the hypothesis that certain unifying manipulations can be performed to increase T cell immunity in immune vulnerable populations to a broad group of pathogens. The second project will develop a novel and effective vaccine platform for safely immunizing both healthy and vulnerable populations against YFV. The second theme will center on "The use of systems biology, functional genomics and genetics to characterize pathogen-host response for biodefense and emerging disease organisms." This theme will include four projects with the overall goal of using systems approaches to identify new targets and therapeutics for Category A-C agents. The goal of the first project a P01 is to use systems approaches to identify common host susceptibility alleles and signaling circuitry that enhance highly pathogenic pneumonic viruses and Ebola virus replication and pathogenesis and to identify key cellular targets and immune correlates that influence severe disease outcomes. The goal of the second project a P01 is focused on defining innate immune mechanisms, therapeutic targets, and antiviral compounds that limit flavivirus infection and pathogenesis. The third project an R01 will use systems approaches to characterize Francisella mutants that exhibit either altered intracellular growth rates or induce cellular apoptosis. The last project an RO1 will use a combination of genetic, biochemical, and computational approaches to elucidate B. pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease.

Public Health Relevance

One focus of this application is to identify age-related immune system defects to develop new vaccines and supplemental therapies to enhance protection of individuals to NIAID Category A-C pathogens. A second goal of this center is to use systems genetic, chemical, and proteomics approaches to identify therapeutic targets for biodefense and emerging diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI081680-04
Application #
8234070
Study Section
Special Emphasis Panel (ZAI1-DDS-M (J2))
Program Officer
Schaefer, Michael R
Project Start
2009-04-20
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
4
Fiscal Year
2012
Total Cost
$7,798,614
Indirect Cost
$1,389,540
Name
Oregon Health and Science University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Smith, Jessica L; Stein, David A; Shum, David et al. (2014) Inhibition of dengue virus replication by a class of small-molecule compounds that antagonize dopamine receptor d4 and downstream mitogen-activated protein kinase signaling. J Virol 88:5533-42
Trobaugh, Derek W; Gardner, Christina L; Sun, Chengqun et al. (2014) RNA viruses can hijack vertebrate microRNAs to suppress innate immunity. Nature 506:245-8
Haick, Anoria K; Rzepka, Joanna P; Brandon, Elizabeth et al. (2014) Neutrophils are needed for an effective immune response against pulmonary rat coronavirus infection, but also contribute to pathology. J Gen Virol 95:578-90
Gibbs, David L; Gralinski, Lisa; Baric, Ralph S et al. (2014) Multi-omic network signatures of disease. Front Genet 4:309
Gardner, Christina L; Hritz, Jozef; Sun, Chengqun et al. (2014) Deliberate attenuation of chikungunya virus by adaptation to heparan sulfate-dependent infectivity: a model for rational arboviral vaccine design. PLoS Negl Trop Dis 8:e2719
Josset, Laurence; Tchitchek, Nicolas; Gralinski, Lisa E et al. (2014) Annotation of long non-coding RNAs expressed in collaborative cross founder mice in response to respiratory virus infection reveals a new class of interferon-stimulated transcripts. RNA Biol 11:875-90
Nikolich-┼Żugich, Janko (2014) Aging of the T cell compartment in mice and humans: from no naive expectations to foggy memories. J Immunol 193:2622-9
Engelmann, Flora; Josset, Laurence; Girke, Thomas et al. (2014) Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model. PLoS Negl Trop Dis 8:e3295
Pal, Pankaj; Fox, Julie M; Hawman, David W et al. (2014) Chikungunya viruses that escape monoclonal antibody therapy are clinically attenuated, stable, and not purified in mosquitoes. J Virol 88:8213-26
Fontaine, Krystal A; Camarda, Roman; Lagunoff, Michael (2014) Vaccinia virus requires glutamine but not glucose for efficient replication. J Virol 88:4366-74

Showing the most recent 10 out of 75 publications