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Principal Investigator: Jacobs, Bertram L.
Institute Receiving Award Arizona State University-Tempe Campus
Location Tempe, AZ
Grant Number R21ES030838
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 23 Sep 2021 to 31 Aug 2023
DESCRIPTION (provided by applicant): Necroptosis is a recently identified caspase-independent cell death pathway that has been shown to act downstream of death receptor signaling or virus infection. Virus infection can be sensed by the host pattern recognition receptor, DAI, which leads to a cascade of events leading to rapid explosive cell death, as a way to prevent virus replication. We have recently shown that DAI not only senses virus infection, but also senses arsenite-induced stress, leading to necroptotic cell death. This broadens the potential importance of DAI mediated necroptosis, well beyond sensing of virus infection, to sensing of virus infection as only one example of stress that can be sensed by DAI. This proposal will better characterize the role of DAI in sensing stress and leading to necroptotic death, and will ask if this pathway is active in primary cells, that have been linked to potential stress-induced necroptosis in vivo. As a developmental proposal this work will justify a larger investment of resources in asking if stress-induced necroptotic death is involved in neurodegenerative, and skin diseases, and in tissue damage associated with ischemia and reperfusion.
Science Code(s)/Area of Science(s) Primary: 01 - Basic Cellular or Molecular processes
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications See publications associated with this Grant.
Program Officer Daniel Shaughnessy
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