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The Henry Lab

We aim to understand how dynamic interactions between cells and their extracellular matrix mediate morphogenesis, and how disruption of cell-matrix interactions leads to disease states.

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Research

Aberrant cell-matrix interactions cause or exacerbate many musculoskeletal disorders such as myopathies, tendonitis, traumatic muscle injuries, arthritis, and sarcopenia. My lab primarily focuses on how signaling between muscle cells and their extracellular matrix mediates musculoskeletal development and homeostasis with the goal of discovering new approaches for treatment of myopathies and traumatic muscle injuries.

Our rigorous focus on mechanisms that mediate changes in the extracellular matrix led us to discover a novel cell adhesion pathway required for laminin polymerization at the myotendinous junction in vivo. We found that Nrk2b-mediated NAD+ synthesis potentiates laminin polymerization during development. We then found that activation of the Nrk2b pathway through NAD+ supplementation is sufficient to augment laminin polymerization and improve muscle structure and function in dystrophic embryos (dystroglycan-deficient zebrafish). This work was published in PLoS Biology and recommended to Faculty of 1000.

Current focuses of our lab include identifying mechanisms of the Nrk2b pathway, characterizing neuromusculoskeletal development in zebrafish models of dystroglycanopathies, and elucidating mechanisms underlying extracellular matrix changes in muscle development, aging, and disease.

Latest Publications

Deleterious impacts of inactivity and beneficial impacts of neuromuscular electrical stimulation on muscle structure and function in the zebrafish model of Duchenne Muscular Dystrophy

Although it is known that inactivity is deleterious for healthy individuals, less is known about the consequences of inactivity on muscle disease. Reduced activity is frequently encouraged for individuals with congenital muscular dystrophies such as Duchenne Muscular Dystrophy (DMD). We used the zebrafish dmd mutant and a longitudinal design to elucidate the consequences of inactivity versus activity on muscle health. Inactivity worsened muscle structure and survival. We designed four neuromuscular stimulation paradigms loosely based on weight lifting regimens. Each paradigm differentially affected muscle structure, function, and survival. Only endurance neuromuscular stimulation (eNMES) improved all outcome measures. We found that eNMES (1) returns gene expression to wild-type levels, (2) increases muscle adhesion to the extracellular matrix (ECM), and (3) remodels the ECM and supports regeneration. Our data indicate that inactivity is deleterious but neuromuscular stimulation can be beneficial, suggesting that the right type of activity may benefit patients with muscle disease.

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