Bioengineering Seminar Series
“Telomere Length Regulation of Muscle Stem Cells in Chronic Injuries”
Foteini Mourkioti, Ph.D.
Department of Orthopaedic Surgery
Perelman School of Medicine
University of Pennsylvania
In chronic injuries such as Duchenne Muscular Dystrophy (DMD), the repeated cycles of muscle damage and repair lead to stem cell dysfunction. We and others previously showed that the muscle stem cell (MuSC) pool becomes less efficient at repairing damage in dystrophic mouse models. While progress has been made over the last decade with respect to potential treatments for DMD, current strategies are focused on treatment of skeletal muscle and do not take muscle stem cells into consideration. We recently demonstrated that telomere shortening is a district feature of dystrophic MuSCs in both mice and DMD patients already at a very young age. We have generated unique mouse tools that allow us to study stem cells within their native tissue environment of live mice and have determined the cellular consequence of telomere shortening in MuSCs. Furthermore, we discovered a previously unknown crosstalk between NF-kappaB and telomeres and determined the function of a telomeric protein in the progression of muscular dystrophy. These findings expand the fundamental knowledge of stem cell biology in diseased muscles. Understanding the molecular link between stem cell functional exhaustion and telomere shortening in DMD will significantly impact the conceptual view of DMD skeletal muscle pathology, providing fresh therapeutic perspectives on disease progression and will likely inform similar mechanisms in musculoskeletal applications with stem cell dysfunction, such as chronic or repeated muscle injuries in aging.
The Mourkioti lab has a long-term interest in understanding the fundamental aspects of skeletal muscle and cardiac function in normal or diseased conditions and in the practical aspects of manipulating these functions by using animal models and tissue engineering approaches for treatment intervention.
The Bioengineering Seminar Series is co-hosted by the Parker H. Petit Institute for Bioengineering and Bioscience, and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.