The objective of this application is to establish POP1 as a key regulator for canonical and non-canonical inflammasome responses, and to define the underlying molecular mechanism using disease models, where selectively the canonical- or non-canonical inflammasome or both inflammasome pathways contribute to the disease. Aim 3 is focused on POP1 as a key inhibitor of ASC danger particle-induced propagation of inflammation. We hypothesize that impaired POP1 expression in patients causes susceptibility to systemic inflammation due to inability to block inflammasomes at several key steps: assembly, release of cytokines and pASC, and the pASC response in bystander cells. We further expect that this can be ameliorated with POP1-based drugs. Here we will investigate the impact of POP1 on this pASC responses and conduct a proof-of-principle treatment approach for systemic inflammatory disease in mice utilizing cell permeable recombinant POP1.
|Effective start/end date||12/1/18 → 11/30/19|
- Cedars-Sinai Medical Center (0001561149//7R01AI20625-04)
- National Institute of Allergy and Infectious Diseases (0001561149//7R01AI20625-04)
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