Comparing the Regulatory Networks Underlying Inflammation in Arthritis & Aging

Project: Research project

Project Details


As the body ages, it becomes more susceptible to chronic inflammatory diseases, such as arthritis. Moreover, rheumatoid arthritis (RA) may be considered a form of premature aging since RA patients exhibit shortened lifespan and increased incidence of cardiovascular disease. Both RA and aging are associated with excess inflammatory cells and heightened TNF signaling. We are interested in whether these similarities hold at the molecular level. We have previously shown that myeloid cells are regulated by epigenomic reprogramming in response to signals in the local environment. These shifts in the regulatory networks can be linked to the action key transcription factors driving condition-specific gene modules, but the epigenomic landscape of aged and arthritis mice have yet to be modeled. We hypothesize that inflammatory monocytes will share regulatory circuits between aging and arthritis. To test this hypothesis, we will compare the regulatory networks of monocyte progenitors in bone marrow and monocyte-derived macrophages in the synovial lining of the joint from mouse models of aging and spontaneous RA. We perform RNA-seq for expression, ATAC-seq for chromatin accessibility, and ChIP-seq for histone modification and integrate these genomic data through computational analysis. We expect to uncover a shared inflammatory signature and evidence of myeloid skewing, a process leading to the overproduction of monocytes, in both aging and arthritis. In the long term, we aim to extend these studies to additional tissues and validate in human cohorts. These results will inform on parallels observed in aging and arthritis and will highlight future targets for therapeutic interventions.
Effective start/end date6/1/175/31/19


  • Arthritis National Research Foundation (AGREEMENT 5/25/18)


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