Macrophages (green) closely associated with regenerating fibers (purple) in dystrophin-deficient skeletal muscle.

Welc Lab
The research lab of Steven Welc, PhD, focuses on understanding the molecular mechanisms that regulate muscle function and pathophysiology. Muscle repair and remodeling is dependent on the coordinated response of diverse cellular systems that comprise the heterogeneous muscle tissue. Specifically, the goal of our research is to understand the complex and coordinated interaction between non-myogenic and myogenic cells that determines the success or failure of muscle regeneration and remodeling. Additionally, we investigate how these reparative processes are misapplied or dysregulated with various pathological conditions (aging, disease, and muscular dystrophy) to inform new treatment strategies for human disease.
Research Interests
Pathophysiological mechanisms of Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a devastating muscle disease caused by genetic mutations to the dystrophin gene. Without dystrophin the mechanical infrastructure of striated muscle cells is compromised causing destabilization of the muscle cell membrane and cellular necrosis. While membrane fragility contributes to the pathophysiology of DMD, it alone cannot account for many pathological features of the disease. The pathophysiology of dystrophin-deficiency is intertwined with multiple secondary defects, including perturbations in the epigenetic regulation of gene expression, as well as considerable involvement of other tissues such as the immune system and stromal cells. Patients could benefit from effective countermeasures that target events downstream of dystrophin-deficiency. Our findings have shown that ⍺Klotho is epigenetically silenced in dystrophic muscles at the onset of dystrophinopathy and that restoring ⍺Klotho expression systemically or via infiltrating bone marrow-derived cells improves regeneration and function. Ongoing investigations, supported by the Muscular Dystrophy Association, are aimed at investigating the mechanisms through which restoring ⍺Klotho reduces fibrosis in dystrophic muscles.
Pathological remodeling of the dystrophin-deficient myocardium (right).
Myeloid cell-mediated mechanisms of muscle regeneration
Inflammatory lesion in injured muscle featured on the cover of The Journal of Immunology (Vol. 205, Issue 6. DOI: 10.4049/jimmunol.2000247)