Sedivy Lab
Principal Investigator: John M Sedivy
Institution: Brown University (Providence, RI)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
PROJECT SUMMARY (PROJECT 1) Retrotransposable elements (RTEs) comprise ~45% of the human genome. Known as ‘mobile DNA’ they can insert into new genomic locations using a 'copy and paste' mechanism. This process, retrotransposition, can be deleterious at multiple levels and host organisms have evolved silencing mechanisms to protect their genomes. Until recently RTEs were thought to be largely silent in somatic cells. In the past 10 years evidence started emerging that somatic RTE activity is more frequent than anticipated, with our group contributing important early evidence. It is now apparent that with aging, multiple host defense mechanisms become compromised, and repetitive sequences in general, not just active RTEs, increase their expression. In the previous funding cycle we discovered that LINE-1 (L1) elements are upregulated in senescent cells and generate cytoplasmically local- ized cDNA reverse transcripts. These cDNAs are perceived as invading virus by the host and trigger a Type-I Interferon (IFN-I) response, which in turn stimulates the innate immune system. We believe this leads to a phe- nomenon known as 'sterile inflammation' or 'inflammaging', a known hallmark of ag…
Active NIH Awards
- 5P01AG051449-10: Project 1: Activation of Alternative L1 Lifecycles in the CNS with age and Alzheimer's Disease (2026)
- 5P01AG051449-10: Core A: Administrative Core (2026)
- 5P01AG051449-10: Role of Retrotransposon Activity in Neurodegeneration and Alzheimer's Disease (2026)
- 5P01AG051449-09: Role of Retrotransposon Activity in Neurodegeneration and Alzheimer's Disease (2025)
- 5P01AG051449-09: Project 1: Activation of Alternative L1 Lifecycles in the CNS with age and Alzheimer's Disease (2025)
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