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Project

Role of EMT-like molecular mechanisms in astrocytes after SCI

Funder: Craig H Neilsen Foundation

Funding period
USD 150 K
Funding amount
Abstract
Astrocytes are key mediators of neuroprotection after spinal cord injury (SCI). Reactive astrocytes bundles generate the astroglial scar. The astrocyte boundary reduces sub-acute damage, but the chronic scar is linked to the inhibition of axonal regeneration. Strategies that augment the beneficial aspects of the astroglial scar formation, while minimizing deleterious aspects, are potentially an important advance to improve functional recovery from SCI. In order to manipulate astrocytes, we must better understand the molecular mechanisms that drive and maintain astrogliosis. The cellular processes underlying astrocytic scar formation resemble wound healing in epithelial tissue. A key process in wound healing is the Epithelial-to-Mesenchymal Transition (EMT), which also occurs in cancer and development. EMT results in changes to cell morphology, adhesion, and the acquisition of a migratory phenotype. Our preliminary analysis at the cellular and molecular levels suggest that SCI-induced astrogliosis is an EMT-like process. The overall objective of this proposal is to establish that the EMT associated mechanisms regulate astrogliosis and scar formation. We will test the overall hypothesis that SCI activates an EMT-like response in astrocytes, and targeting this response can modify astrogliosis, scar formation, and functional recovery. The successful completion of these studies is expected to establish that astrogliosis and scar formation following SCI are EMT-like processes. This expected finding will represent a significant paradigm shift in understanding the molecular mechanisms that drive astrogliosis following SCI. These findings will also provide the foundation to apply the resources generated to manipulate EMT in cancer, development, and wound healing towards novel interventions for SCI. The proposed studies and training plan will lay the groundwork for me to establish an independent, translational research program focused on EMT as a therapeutic target for SCI. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    0601 Biochemistry and Cell Biology

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Regenerative Medicine

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Cancer

  • RCDC

    Neurodegenerative

  • HRCS RAC

    1.1 Normal biological development and functioning

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science