PhD Proposal by Lauren Hymel

Event Details
  • Date/Time:
    • Thursday April 14, 2022
      12:00 pm - 2:00 pm
  • Location: EBB 3029
  • Phone:
  • URL: BlueJeans
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Summaries

Summary Sentence: Modulation of Sphingosine-1-Phosphate Receptor Signaling as a Regenerative Immunotherapy for Volumetric Muscle Loss Injury

Full Summary: No summary paragraph submitted.

Lauren Hymel
BME PhD Proposal Presentation

Date:2022-04-14
Time: 12 PM EST
Location / Meeting Link: EBB 3029 / https://bluejeans.com/580893647/8089

Committee Members:
Edward A. Botchwey, PhD (Advisor) Andrés J. García, PhD Young C. Jang, PhD Nick J. Willett, PhD Valeria T. Milam, PhD Timothy Hla, PhD


Title: Modulation of Sphingosine-1-Phosphate Receptor Signaling as a Regenerative Immunotherapy for Volumetric Muscle Loss Injury

Abstract: Extremity trauma is a significant clinical challenge among both civilian and military populations, particularly in cases that result in volumetric muscle loss (VML). Current standards of treatment for VML fail to successfully restore muscle function after injury and result in fibrosis rather than newly formed muscle fibers. Many approaches aimed to treat VML fail to pay attention to the local endogenous immune response of the host which underlies the chronic inflammation and fibrotic signaling characteristic of VML pathology. An increasingly recognized regulator of immune function upon disruption of tissue homeostasis is sphingosine-1-phosphate (S1P). S1P is a bioactive sphingolipid produced during inflammation and acts as a potent chemoattractant toward sites of injury. S1P signals through its 5 known G protein- coupled receptors (S1PR1-5) to elicit a range of cellular responses governing complex functions such as cell migration, vascular integrity, and fibrosis. Importantly, S1PR3 has been implicated in propagating TGFβ-mediated tissue fibrosis, and our previous studies reveal a crucial role for S1PR3 in cellular niche occupancy versus egress. The central hypothesis of this work is that critically sized VML injuries will present with prolonged immune cell retention in the muscle due to increased concentrations of S1P; however, modulation of S1PR signaling will attenuate chronic inflammation and reduce pro-fibrotic signaling to enhance muscle regeneration and functional recovery. Using a pre-clinical model of VML injury, the role of S1P signaling on aberrant immune cell retention and macrophage-mediated fibrosis will be assessed in Aim 1. In Aim 2, the contribution of S1PR3 in tethering immune cells within the muscle injury niche will be evaluated. Further, local antagonism of S1PR3 will be achieved via delivery of a pharmacological inhibitor from nanofibrous polyethylene glycol/hyaluronic acid scaffolds to promote muscle regeneration and abrogate fibrotic responses. This work will develop a novel, anti-fibrotic regenerative immunotherapy and demonstrate how S1P receptor modulators can be re-purposed to locally target endogenous repair cells for a wide range of inflammatory conditions.

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In Campus Calendar
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Graduate Studies

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Keywords
Phd proposal
Status
  • Created By: Tatianna Richardson
  • Workflow Status: Published
  • Created On: Apr 1, 2022 - 5:03pm
  • Last Updated: Apr 1, 2022 - 5:03pm