phone: (310) 206-3395
office: 1135 TLSB
research interests: Pathophysiological mechanisms in muscular dystrophy
Research in the Tidball lab is directed toward understanding processes that regulate skeletal muscle wasting and regeneration. Exploring the mechanisms through which the immune system can modulate skeletal muscle wasting, injury, regeneration and growth is a particular focus of the lab. Discoveries in the Tidball lab over the past 20 years have shown that immune cells, especially myeloid cells, play a major role in modulating muscle injury and repair that occur in chronic, muscle wasting diseases and following acute injuries. For example, their findings have shown that macrophages and eosinophils are key effector cells in the pathogenesis of Duchenne muscular dystrophy. Ongoing investigations in the lab are revealing the identity of specific molecules released by myeloid cells that promote muscular dystrophy. However, recent findings in the lab have also shown that regulatory interactions between cytotoxic, M1 macrophages in dystrophic muscle and anti-inflammatory, M2a macrophages are important in regulating the balance between the death of dystrophic muscle and regenerative processes. This work shows that the experimental manipulation of the balance between the functions of M1 and M2a macrophages can affect the severity of muscular dystrophy, suggesting that manipulation of macrophage phenotype in vivo may have potential therapeutic value for the treatment of the disease. Other investigations in the Tidball lab concern the proteolytic mechanisms that contribute to sarcopenia, the process through which muscle wasting occurs during the aging process. The Tidball lab uses proteomic approaches to identify specific, key substrates in proteolytic cascades that lead to muscle wasting. Subsequent experimentation relies on genetic manipulations designed to disrupt the cascades, with the goal of reducing sarcopenia. Identification of the mechanisms through which pro-inflammatory, Th1 cytokines can modulate muscle wasting during aging by influencing the state of activation proteases that drive muscle wasting is also major component of the sarcopenia investigations in the Tidball lab.
Wehling-Henricks, M, Welc, S., Samengo, G., Rinaldi, C., Lindsey, C., Wang, Y., Lee, J., Kuro-o, M. and J. G. Tidball., "Macrophages escape Klotho gene silencing in the mdx mouse model of Duchenne muscular dystrophy and promote muscle growth and increase satellite cell numbers through a Klotho-mediated pathway", Human Molecular Genetics, 27 : 14-29 (2018) .
Tidball, J.G., "Regulation of muscle growth and regeneration by the immune system", Nature Reviews Immunology, 17 : 165-178 (2017) .
Wehling-Henricks, M., Li, Z., Lindsey, C., Wang, Y., Welc, S.S., Ramos, J.N., Khanlou, N., Kuro-O, M., Tidball, J.G., "Klotho gene silencing promotes pathology in the mdx mouse model of Duchenne muscular dystrophy", Human Molecular Genetics, 1-18 (2016) .
Wang, Y., Wehling-Henricks, M., Samengo, G. and J.G. Tidball, "Increases of M2a macrophages and fibrosis in aging muscle are influenced by bone marrow aging and negatively regulated by muscle-derived nitric oxide", Aging Cell, 14 : 678-688 (2015) .
Tidball, J.G. and M. Wehling-Henricks, "Shifts in macrophage cytokine production drive muscle fibrosis", Nature Medicine, 21 : 665-666 (2015) .
Tidball, J.G. and S. Welc, "Macrophage-derived IGF-1 is a potent coordinator of myogenesis and inflammation in regenerating muscle", Molec. Therapy, 23 : 1134-1135 (2015) .
Tidball, J.G. and C. Bertoni, "Purloined mechanisms of bacterial immunity can cure muscular dystrophy", Cell Metabolism, 20 : 927-929 (2014) .
Villalta, S.A., W. Rosenthal, L. Martinez, I. Kramerova, T. Sparwasser, J.G. Tidball, M. Margeta, M. Rosenblum, M. Spencer and J.A. Bluestone., "Regulatory T cells suppress muscle inflammation and injury during muscular dystrophy", Science Translational Medicine, 6 (258): 258ra142- (2014) .
Tidball, J.G. and M. Wehling-Henricks., "Nitric oxide synthase deficiency and the pathophysiology of muscular dystrophy", J. Physiol. (Lond.), 592 : 4627-4638 (2014) .
Tidball, J.G., Dorshkind, K. and M. Wehling-Henricks., "Shared signaling systems in myeloid cell-mediated muscle regeneration", Development, 141 : 1184-1196 (2014) .