Dong Gun Oh
BME PhD Defense Presentation

Date: 2026-05-29
Time: 11:00 AM - 1:00 PM
Location / Meeting Link: HSRB2 N100 / https://emory.zoom.us/j/92597159515

Committee Members:
Laura Hansen, PhD (advisor); W. Robert Taylor, MD/PhD; Hanjoong Jo, PhD; Hyojung Choo, PhD; Luke Brewster, MD/PhD 


Title: Investigating Changes in Satellite Cell Proliferation and Angiogenic Potential in Response to Exercise Therapy

Abstract:
Supervised exercise therapy (SET) has emerged as a primary, non-invasive strategy to improve functional mobility in patients with Peripheral Artery Disease (PAD). Despite its widespread adoption, the cellular mechanisms driving this functional rehabilitation remain poorly understood. In particular, the role of skeletal muscle satellite cells (SCs) as active biological mediators that translate the mechanical and metabolic stress of exercise into tissue regeneration has been largely overlooked in the context of PAD pathophysiology. The chronically ischemic microenvironment characteristic of PAD imposes persistent stress that disrupts SC function and impairs the intercellular signaling networks required for vascular and structural adaptation. Furthermore, SET is not universally therapeutic; some patients paradoxically develop exacerbated ischemic myopathy with no functional improvement. The mechanisms underlying this variability in therapeutic responsiveness also remain poorly defined. This dissertation investigates the cellular, paracrine, and transcriptomic adaptations of SCs to elucidate the mechanisms governing SET-mediated rehabilitation and the divergent clinical responses to exercise therapy. In Aim 1, the temporal dynamics of SC proliferation and transcriptomic remodeling in response to exercise were characterized using an aged murine model. In Aim 2, the isolated and synergistic effects of exercise-induced stimuli, specifically hypoxia and lactate accumulation, on SC behavior were examined in vitro. In Aim 3, divergent regenerative trajectories and intercellular communication networks associated with heterogenous clinical outcomes in response to SET were analyzed in human PAD skeletal muscle using single-nuclei transcriptomics. Collectively, these studies demonstrate that transient exercise-induced stimuli can promote beneficial SC-mediated angiogenesis and oxidative muscle remodeling, whereas the hostile ischemic microenvironment in PAD drives SC functional exhaustion, maladaptive glycolytic remodeling, and persistent denervation in the patients experienced worsened clinical outcome post-exercise. These findings establish a mechanistic framework linking SC dysfunction to divergent rehabilitation outcomes and provide a critical foundation for the development of precision regenerative therapies targeting ischemic skeletal muscle in PAD.