Fry, Christopher

Lab Research Activities

Our research focuses on elucidating the mechanisms that regulate skeletal muscle plasticity to establish interventions to maintain skeletal muscle strength and mass during conditions of muscle wasting. Much of our current work involves studying the contribution of various progenitor cells to myofiber adaptation and extracellular matrix remodeling in the context of pathology and injury. Our lab utilizes human, transgenic mouse, and cell culture approaches to develop novel and translational therapeutic interventions in the etiology of skeletal muscle pathology. Specific projects in our lab seek to elucidate molecular adaptations (RNA, chromatin association, methylation) that occur in lower limb skeletal muscle following knee injury. After a knee ligament injury, a cascade of muscle deficits occur, culminating in atrophy and weakness. Not only are these deficits problematic for recovery, but they predispose to the development of knee osteoarthritis.

Additionally, we explore muscle adaptation in older adults and older pre-clinical mouse studies. Specifically, we study regulation of extracellular matrix remodeling in aged skeletal muscle as a determinant of muscle plasticity. With age, we observe a less dynamic extracellular matrix, which we posit is a driver of poorer muscle adaptation in general. We seek to identify novel targets that restore more dynamic extracellular matrix remodeling in aged skeletal muscle.

Single myonuclear sequencing from human vastus lateralis after anterior cruciate ligament (ACL) injury

Anterior cruciate ligament (ACL) tear leads to protracted and persistent quadriceps muscle atrophy and weakness. The ambiguity surrounding the cellular and molecular determinants of muscle atrophy and weakness following ACL injury has limited rehabilitation success, leading to prolonged deficits and poor functional recovery. This is an exploratory project that aims to characterize nuclear changes in humans with an ACL injury before and after reconstruction surgery to identify potential therapeutic targets. Unbiased interrogation of dysregulated genes at a single nuclei resolution will allow for the identification of novel targets and pathways that underlie muscle deficits following knee injury.

Participants

PI – Christopher Fry

Junior Faculty – Allison M Owen

Students

Alexander R Keeble, graduate in Physiology, Added on MCC 02/06/2023 

Nicholas T Thomas, graduate in Physical Therapy, Added on MCC 02/06/2023 

Computational Methods

Rstudio, Matlab, CellRanger (run in linux), sequence aligners (ie. Seurat package in R), DESEQ2, Monocle 2 – all software is commercially available. 

Collaborators

John McCarthy (UK)

Yuan Wen (UK)

Grants

Publications