Skeletal muscle comprising ~ 40% of human mass is a contractile tissue that enables all motor movements and respiration. Muscle typically has a remarkable ability to repair upon injury due to the muscles’ resident stem cells, called satellite cells (SC). SCs repair damaged skeletal muscle by exiting quiescence, and actively proliferating in response to signals from the SC niche, and then either differentiating and fusing to damaged myofibers or with each other to form new myofibers, while a small number of SCs then reinstate quiescence to renew the population. However, misregulation of these SC responses is detrimental to the quantity of myogenic progenitors and the regenerative capacity of muscle.
While many extrinsic circulating systemic factors regulate satellite cell behavior, little progress has been made to understand how the mechanical properties of the niche can impact satellite cell function. Recently, it has been found that muscle becomes dramatically stiffer after both injury and exercise. Yet, it is not known how these physical alterations influence the intrinsic signaling pathways of satellite cells. The objective of my thesis is to probe the physical stimulus and mechanosensing pathways on satellite cell behavior through dynamically changing polymer networks and in vivo injury models. These novel platforms will tease apart the complex, multi-dimensional cell-matrix interactions within the injured muscle microenvironment. Understanding how external signals dictate SC behavior will further elucidate potential signaling pathways for future pharmacological targets to enhance muscle regeneration.
Figure 1. On demand stiffening gels through click chemistry to probe mechanotransduction in muscle stem cells. A SPAAC reaction occurs between a strained alkyne such as dibenzocyclooctne (DBCO) and azide to react rapidly at physiological conditions without a catalyst. A SPAAC network with excess DBCO molecules can be further crosslinked together by conjugating the free DBCO moieties with light and photoinitiator. These hydrogel platforms are used to interrogate the mechanotransduction pathways in muscle stem cells.
I am a 6th year MD/PhD Candidate in the Medical Scientist Training Program at the University of Colorado School of Medicine. I am now pursing my PhD in Chemical and Biological Engineering at the University of Colorado, Boulder with Dr. Kristi Anseth as my thesis advisor and I am co-advised by Dr. Bradley Olwin in the Molecular, Cellular, and Developmental Biology Department. I received a bachelor of science in Bioengineering from the University of California, Berkeley in May 2012. After graduation, I worked in Dr. Sheldon Miller and Dr. Kapil Bharti's lab as a Postbac IRTA Fellow at the National Institutes of Health focusing on stem cell differentiation into retinal tissues. I have an emphasis in cellular and tissue engineering and continue to apply these skills as I study muscle stem cells in the Anseth Lab.