Shannon Anderson

PhD Proposal Presentation

Date: Monday, January 28th

Time: 2 pm

Location: EBB CHOA room

Advisors:

Professor Young C. Jang, Ph.D. (Georgia Tech, Biosciences)

Professor Nick J. Willett, Ph.D. (Emory, Orthopedics)

Thesis Committee Members:

Professor Edward A. Botchwey, Ph.D. (Georgia Tech, BME)

Professor Johnna S. Temenoff, Ph.D. (Georgia Tech, BME)

Professor Khalid Salaita, Ph.D. (Emory, Chemistry)

Professor Jarrod A. Call, Ph.D. (UGA, Kinesiology)

Title: Re-engineering the muscle stem cell niche following volumetric muscle loss

Abstract: Skeletal muscle possesses a remarkable regenerative capacity due to the presence of an adult muscle stem cell (MuSC) population, called satellite cells. However, this regenerative response is significantly diminished after volumetric muscle loss (VML), which results from large, traumatic injuries in which the muscle defect size exceeds the regenerative threshold. Clinically, the current standard of care for VML remains focused on limb salvage, which often leads to permanent disability. Therefore, there is a clinical need for interventions which promote functional muscle recovery following VML. While tissue engineered strategies and cell transplantation show promise as alternative therapeutic strategies, there is a lack of understanding in the dysregulated cellular dynamics which result in pathological healing following these traumatic VML injuries. The overall objective of this thesis is to re-engineer the MuSC niche as a therapeutic for functional recovery after VML. The overarching hypothesis is that loss of function following VML is the result of a critically damaged and temporally dysregulated MuSC niche environment; by re-engineering this environment we will be able to substantially improve functional muscle regeneration. This will be achieved through three specific aims: (1) to define a critically sized VML injury in the mouse quadriceps, (2) modulate the inflammatory and regenerative cell dynamics following VML, and (3) to engineer a VML therapeutic strategy which recapitulates a pro-regenerative MuSC niche. Upon completion, this thesis will fill a gap in knowledge about critically sized skeletal muscle defects, the effect of these injuries on local regenerative dynamics, and ultimately inform a therapeutic strategy to enhance muscle regeneration after VML injuries.