email: jtidball@physci.ucla.edu
phone: (310) 206-3395
office: 5833 LSB
homepage: http://www.physci.ucla.edu/DMD/
research interests: Cell Biology of Muscle Growth, Adaptation and Disease
Research Interests
A major project in our lab concerns the pathophysiology of muscular dystrophy (dystrophinopathy). Our recent findings have shown that the immune system plays a significant role in promoting dystrophinopathy, and that immune-based interventions can significantly reduce dystrophic muscle pathology. Our continuing efforts are directed toward identifying the key effector cells and molecules involved in promoting the immune contribution to the disease, and examining the interplay between those effectors. Our technical approaches include the generation and analysis of transgenic, dystrophic mice so that the effects of increased or decreased expression of selected effector molecules can be assessed. We also examine the systemic effects of experimental depletions of selected immune cell populations and the efficacy of selected, pharmaceutical interventions on the progress of the disease. In other studies, we are studying the mechanisms through which skeletal muscles transduce mechanical information to chemical signals that result in changes in the structure and function of muscle. Although many processes by which cells can perceive changes in their environment through chemical signals are known, we have little understanding of how information concerning the mechanical world is perceived by cells to regulate their function. Much of our current work in this area focusses on the role of nitric oxide in mechanochemical signal transduction in muscle. Our technical approaches include the systemic evaluation of transgenic mice that we have generated in which the normal expression of nitric oxide is perturbed.
Selected Publications
Tidball, J.G. and M. Wehling-Henricks. 2007. Macrophages promote muscle membrane repair and muscle fiber growth and regeneration during modified muscle loading in mice in vivo Journal of Physiology (Lond.) 578.1 327-336 .
Acharyya, S., S.A. Villata, N. Bakkar, T. Bupha-Intr, P.M.L. Janssen, M. Carathers, M. Karin, Z. Li, A. Beg, S. Ghosh, Z. Sahenk, M. Weinstein, K.L. Gardner, J.A. Rafael-Fortney, J.G. Tidball, A.S. Baldwin and D.C. Guttridge. 2007. IKK/NF-kB signaling interplay in macrophages and myofibers promotes muscle wasting in Duchenne muscular dystrophy J. Clin. Invest 117 889-901 .
Tidball, J.G.. 2005. Mechanical signal transduction in skeletal muscle growth and adaptation Journal of Applied Physiology 98 1900-1908 .
Nguyen, H.X., A.J. Lusis and J.G. Tidball. 2005. Null mutation of myeloperoxidase in mice prevents mechanical activation of neutrophil lysis of muscle cell membranes in vitro and in vivo Journal of Physiology (Lond.) 565.2 403-413 .
Wehling-Henricks, M., M.C. Jordan, K.P. Roos, B. Deng and J.G. Tidball. 2005. Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium Human Molecular Genetics 14 1921-1933 .
Tidball, J.G. and M. Wehling-Henricks. 2005. Damage and inflammation in muscular dystrophy: potential implications and relationships to autoimmune myositis Current Opinion in Rheumatology 17 707-713 .
Shiao, T., A. Fond, B. Deng, M. Wehling-Henricks, M.E. Adams, S.C. Froehner, and J. G. Tidball.. 2004. Defects in neuromuscular junction structure in dystrophic muscle are corrected by expression of a NOS transgene in dystrophin-deficient muscles, but not in muscles lacking alpha- and beta-1-syntrophins Human Molecular Genetics 13 1873-1884 .
Tidball, J.G. and M. Wehling-Henricks. 2004. Expression of a NOS transgene in dystrophin-deficient muscle reduces muscle membrane damage without increasing the expression of membrane-associated cytoskeletal proteins Molecular Genetics and Metabolism 82 312-320 .
Kramerova, I., E. Kudryashova, J.G. Tidball, and M.J. Spencer. 2004. Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro Human Molecular Genetics 13 1373-1388 .
Wehling-Hendricks, M., J.J. Lee and J.G. Tidball. 2004. Prednisolone decreases cellular adhesion molecules required for inflammatory cell infiltration in dystrophia-deficient muscle Neuromuscular Disorders 14 483-490 .