Steven S. Welc, PhD

Research in the Welc Lab focuses on understanding the molecular mechanisms that determine muscle homeostasis, regeneration, and remodeling. The focus of our investigations is on the regulatory interactions of myogenic and non-myogenic cells that determine skeletal and cardiac muscle health. We have a specific interest in the central role that the immune system plays in regulating muscle pathophysiology. Although immune cell populations in muscle can be complex, they are dominated by macrophages, which are present in low concentrations in healthy tissue but can rapidly accumulate in response to injury or disease. These are motile cells capable of highly-specific targeting to areas of pathology and can secrete an array of soluble factors that act directly on muscle cells to promote regeneration and growth. Macrophages are required for normal muscle repair, but can be misapplied in disease to orchestrate devastating pathological interactions with fibrogenic cells facilitating muscle fibrosis. Toward this end, our laboratory is also interested in the pathological role of fibroblasts in the progression of muscle disease. A major goal of our lab is to identify the mechanisms that promote or dysregulate the reparative processes of muscle and then build on that knowledge to develop novel therapeutics with translational implications in conditions of aging, acute trauma, modified-use and disease.

We recently reported a novel therapeutic strategy by which immune cells can be exploited as natural vectors to deliver therapeutic transgenes for the treatment of muscular dystrophy. Welc SS… Tidball JG et al. Targeting a therapeutic LIF transgene to muscle via the immune system ameliorates muscular dystrophy. Nat Comm, 10(1): 2788 (2019).

Welc S.S. Wehling-Henricks M. Antoun J. Ha T.T. Tous I. & Tidball J.G. (2020). Differential effects of myeloid cell PPARδ and IL-10 in regulating macrophage recruitment, phenotype, ang regeneration following acute muscle injury. J Immunol, 205(6), 1664-1677.

Welc S.S. Wehling-Henricks M. Kuro-o M. Thomas K.A. & Tidball J.G. (2020). Modulation of Klotho expression in injured muscle perturbs Wnt signaling and influence the rate of muscle growth. Exp Physiol, 105, 132-147.

Welc S.S. Flores I. Wehling-Henricks M. Ramos J. Wang Y. Bertoni C. & Tidball J.G. (2019). Targeting a therapeutic LIF transgene to muscle via the immune system ameliorates muscular dystrophy. Nat Commun, 10(1), 2788.

Wang Y. Welc S.S. Wehling-Henricks M. & Tidball J.G. (2018). Myeloid cell-derived tumor necrosis factor-alpha promotes sarcopenia and regulated muscle cell fusion with aging muscle fibers. Aging Cell, 17(6), e12828.

Wehling-Henricks* M. Welc* S.S. Samengo G. Rinaldi C. Lindsey C. Wang Y. Lee J. Kuro-o M. & Tidball J.G. (2018). Macrophages escape Klotho gene silencing in the mdx model of Duchenne muscular dystrophy and promote muscle growth and increase satellite cell numbers through a Klotho-mediated pathway. Hum Mol Genet, 27(1), 14-29. * Co-First Authors.

Tidball J.G., Welc S.S. & Wehling-Henricks M. (2018). Immunobiology of inherited muscular dystrophies. Compr Physiol, 8(4), 1313-56.