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 #
5U54AI081680-02
Application #
7807162
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
2010-03-01
Budget End
2011-02-28
Support Year
2
Fiscal Year
2010
Total Cost
$8,064,974
Indirect Cost
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
Pryke, Kara M; Abraham, Jinu; Sali, Tina M et al. (2017) A Novel Agonist of the TRIF Pathway Induces a Cellular State Refractory to Replication of Zika, Chikungunya, and Dengue Viruses. MBio 8:
Uhrlaub, Jennifer L; Smithey, Megan J; Nikolich-┼Żugich, Janko (2017) Cutting Edge: The Aging Immune System Reveals the Biological Impact of Direct Antigen Presentation on CD8 T Cell Responses. J Immunol 199:403-407
Bottomly, Daniel; Wilmot, Beth; McWeeney, Shannon K (2015) plethy: management of whole body plethysmography data in R. BMC Bioinformatics 16:134
Gralinski, Lisa E; Ferris, Martin T; Aylor, David L et al. (2015) Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross. PLoS Genet 11:e1005504
Okumura, Atsushi; Rasmussen, Angela L; Halfmann, Peter et al. (2015) Suppressor of Cytokine Signaling 3 Is an Inducible Host Factor That Regulates Virus Egress during Ebola Virus Infection. J Virol 89:10399-406
LaBeaud, A Desiree; Banda, Tamara; Brichard, Julie et al. (2015) High rates of o'nyong nyong and Chikungunya virus transmission in coastal Kenya. PLoS Negl Trop Dis 9:e0003436
Mirrashidi, Kathleen M; Elwell, Cherilyn A; Verschueren, Erik et al. (2015) Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection. Cell Host Microbe 18:109-21
Davis, Zoe H; Verschueren, Erik; Jang, Gwendolyn M et al. (2015) Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Mol Cell 57:349-60
Sali, Tina M; Pryke, Kara M; Abraham, Jinu et al. (2015) Characterization of a Novel Human-Specific STING Agonist that Elicits Antiviral Activity Against Emerging Alphaviruses. PLoS Pathog 11:e1005324
Sanchez, Erica L; Lagunoff, Michael (2015) Viral activation of cellular metabolism. Virology 479-480:609-18

Showing the most recent 10 out of 124 publications