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Mahir Mohiuddin
BME PhD Proposal Presentation
Date: Thursday, October 17th, 2019
Time: 2:00 pm
Location: HSRB E260
Committee Members:
Young C. Jang, PhD (Advisor)
Nick J. Willett, PhD
Luke P. Brewster, MD, PhD
Hee Cheol Cho, PhD
Carlos A. Aguilar, PhD
Title: Investigating the Relationship Between Muscle Stem Cells and the Mitochondrial Network in Ischemic Skeletal Muscle
Abstract:
Peripheral artery disease (PAD) is a progressive vascular disease that manifests abnormal perfusion to the limb muscles and affects up to 12% of American adults. Through ischemic stress, PAD induces skeletal muscle regeneration and exhibits mitochondrial dysfunction of the muscle fiber. Although the muscle stem cell (MuSC) is indispensable for skeletal muscle regeneration and remodeling of the myofiber, it is currently unknown how MuSCs regulate the myofiber’s mitochondrial network. Thus, the overall objective of this thesis is to explore the role of MuSCs in remodeling of the mitochondrial network and function following ischemic injury. Because initial studies have shown that MuSC-driven adult myogenesis parallels mitochondrial biogenesis, the overarching hypothesis is that ischemic stress induces MuSCs and MuSC-derived myonuclei to restore the mitochondrial reticula and bioenergetic function within the myofiber. This will be achieved through three specific aims: (1) to characterize the temporal response of the MuSC and mitochondrial network in ischemic myofibers, (2) to investigate MuSC-mediated mitochondrial transfer in the restoration of the mitochondrial network in ischemic myofibers, and (3) to examine the effect of preconditioning on the ability of MuSCs to restore the mitochondrial network and function of ischemic myofibers. Upon completion, this thesis will fill a gap in knowledge about the relationship between MuSCs and the mitochondrial network in ischemic myofibers and ultimately demonstrate the therapeutic value of a novel approach to enhance skeletal muscle regeneration and repair the mitochondrial network through MuSC-mediated mitochondrial transplantation.