| Description |
Title: "Quantification and Control of Dermal Tissue Signalling During Injury Repair"
Committee:
Allyson Sgro, PhD – BME (Advisor, Chair)
Xue Han, PhD – BME
John Ngo, PhD – BME
Thomas Gilmore, PhD – Biology
Abstract:
Dermal wound healing is a complex process which requires coordinated intracellular signaling across multiple organ systems, ideally culminating in extracellular matrix (ECM) repair and reepithelization of the skin. Disruptions in cellular signaling due to disease or infection can disrupt tissue regeneration, leading to scarring or chronic wounds. Active control of cellular signaling during injury repair could override and correct disrupted cellular signaling, or potentially jump start stalled wound healing. In this work, we propose the first step towards active control of injury repair at the level of intracellular signaling by using optogenetics to modulate calcium, a key signaling molecule, to regulate ECM repair in a dermal tissue microchip model. We will first characterize the biochemical and mechanical signals resulting from injury that trigger calcium signaling in the tissue. Next we will measure two potential outputs of calcium signaling; fibronectin secretion via NF-KB/NFAT mediated signaling, and cellular contractility via calmodulin and myosin light chain kinase activity. Lastly, we will use this understanding of calcium signaling in conjunction with the optogenetic calcium channel OPN4 to recover tissue repair when the native signaling pathway is inhibited and to more broadly characterize the relationship between input calcium signal and tissue repair.
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