Please enable JavaScript or talk to your local administrator to get JavaScript enabled.


The Role of Myeloid ATF3 in Neuroprotection following SCI

Funder: Craig H Neilsen Foundation

Funding period
USD 600 K
Funding amount
Spinal cord injury (SCI) is a progressive disease. Secondary damage following SCI continues over weeks or months, and is characterized by an incompletely-understood inflammatory response mediated by resident and infiltrating immune cells. Activating Transcription Factor 3 (ATF3) induction has been shown to attenuate pro-inflammatory cytokine in immune cells epigenetically via remodelling chromatin accessibility. Two FDA-approved drugs, tamoxifen (TAM) and dimethyl fumarate (DMF) induce ATF3 in macrophages when activated, and this activation attenuates inflammatory cytokine production (preliminary data). The overall objective is to investigate the regulation and roles of ATF3 in neuroprotection conferred by TAM and DMF. We will use genetic and pharmacological interventions, behavioural and histological analyses, and bioinformatic methods to meet the following specific aims:
Aim 1. To determine the signaling pathways upstream of ATF3 induction by TAM and DMF. We will use activators and inhibitors of TAM and DMF-binding proteins to determine how they initiate ATF3 expression in vitro.
Aim 2. To determine the role of ATF3 in neuroprotection in vivo following SCI. We will use a CX3CR1-Cre mouse line crossed with an ATF3 floxed line to remove ATF3 from resident microglia and circulating macrophages. This will determine the effects of ATF3 deletion on neuroprotection following TAM/DMF treatment in mice with spinal contusions.
Aim 3. To determine the epigenetic and downstream effects of ATF3 induction in myeloid cells by TAM/DMF. We will use ATAC-seq to identify open chromatin (including enhancers) in FACS-purified macrophages and microglia from animals with SCI (ATF3 wild-type or ATF3-null), and SCI plus TAM/DMF. We will also carry out single-cell RNA-seq on macrophages and microglia isolated from the same groups to determine the effect of TAM/DMF-induced ATF3 on the microglial transcriptome. (CHN: SCIRTS chn:wdg)
Similar projects All >
Sorted by: Start Date
Project list item
Toll-like receptor 4 signaling in chronic neuropathic pain after SCI

Craig H Neilsen Foundation to Armin Blesch, Fletcher White, Zhiyong Tan

USD 300,000
2018 - 2021
Project list item
Targeting B cells and Bruton's Tyrosine Kinase for SCI Therapeutics

Craig H Neilsen Foundation to James W Geddes, Chen-Guang Yu, John Carib Gensel

USD 300,000
2016 - 2019
Project list item
MicroRNA-155 is a novel target for ameliorating SCI-induced neuropathic pain and locomotor deficits

Craig H Neilsen Foundation to Steven Maier, Andrew Gaudet

USD 300,000
2016 - 2019
Project list item
Alternative activation of microglia to promote regeneration

Craig H Neilsen Foundation to David P. Stirling, David P. Stirling

USD 300,000
2015 - 2018
Project list item
An immunomodulatory therapy for spinal cord injury

Craig H Neilsen Foundation to John Carib Gensel, David Feola

USD 299,018
2014 - 2016



    1107 Immunology

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC


  • RCDC

    Spinal Cord Injury

  • RCDC


  • RCDC



    Inflammatory and Immune System


    2.1 Biological and endogenous factors

  • Health Research Areas


  • Broad Research Areas

    Basic Science