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James Tidball, Ph.D.

Email Address:
jtidball@physci.ucla.edu

Work Address:
Laboratory
Life Sciences
Dept of Physiological Science
UCLA
Los Angeles, CA 90095
UNITED STATES

Office
Dept of Pathology and Laboratory Medicine
UCLA
Los Angeles, CA 90095
UNITED STATES

Lab Number:
(310) 206-3395
Office Phone Number:
(310) 206-3395



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Department / Division Affiliations
Distinguished Professor, Integrative Biology and Physiology
Chair, Molecular, Cellular, and Integrative Physiology IDP
Professor, Pathology and Laboratory Medicine
Member, ACCESS Program: Dept. of Molecular, Cell & Integrative Physiology, Access Immunity, Microbes, and Molecular Pathogenesis Home Area, Access Molecular, Cellular and Integrative Physiology Home Area, Access Neuroscience Home Area, Brain Research Institute
Faculty, Biomedical Engineering IDP, Cellular and Molecular Pathology PhD Program

Bio:

Interactions between skeletal muscle and the immune system. 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 the immune system influences the wasting of skeletal muscle that occurs during aging, a process called sarcopenia. We are particularly interested in identifying the mechanisms through which pro-inflammatory cytokines affect muscle wasting and regeneration, and identifying strategies to slow the wasting process.

Publications:

Wehling-Henricks, M., M. C. Jordan, T. Gotoh, W. W. Grody, K. P. Roos and J. G. Tidball Arginine metabolism by macrophages promotes cardiac and muscle fibrosis in mdx muscular dystrophy. PLoS One 2010; 5(5): e10763. doi:10.1371/journal.pone.0010763.
Tidball, J.G. and S.A. Villalta Interactions between muscle and the immune system regulate muscle growth and regeneration. Amer. J. Physiol 2010; 298: R1173-1187.
Tidball, J.G. and M. Wehling-Henricks Inflammatory mechanisms in genetic neuromuscular disorders. Inflammatory and autoimmune disorders of the nervous system in children 2009; 455-479.
Wehling-Henricks, M., M. Oltmann, C. Rinaldi, K. H. Myung, and J. G. Tidball Loss of positive allosteric interactions between neuronal nitric oxide synthase and phosphofructokinase contributes to defects in glycolysis and increased fatigability in muscular dystrophy. Human Molecular Genetics 2009; 18: 3439-3451.
Deng, B., D. Glanzman and J.G. Tidball Nitric oxide generated by muscle corrects defects in hippocampal neurogenesis and neural differentiation caused by muscular dystrophy. Journal of Physiology 2009; 587: 1769-1778.
Tidball, J.G. and S.A. Villalta Nitric oxide may prompt calcium leakage in dystrophic muscle. Nature Medicine 2009; 15: 243-244.
Villalta, S.A., H.X. Nguyen, B. Deng, T. Gotoh and J.G. Tidball Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy. Human Molecular Genetics 2009; 18: 482-496.
Tidball, J.G. Inflammation in skeletal muscle regeneration. Skeletal muscle repair and regeneration 2008; 243-268.
Wehling-Henricks, M., Sokolow, S., Lee, J.J., Myung, K.H., Villalta, A., and J.G. Tidball Major basic protein-1 promotes fibrosis of dystrophic muscle and attenuates the cellular immune response in muscular dystrophy. Human Molecular Genetics 2008; 17:2280-2292: .
Hao, M., K. Akrami, K. Wei, C. De Diego, N. Che, J.H. Ku, J.G. Tidball, M.C. Graves, P.B. Shieh and F. Chen Muscleblind-like 2 (Mbnl2) -deficient mice as a model for myotonic dystrophy. Developmental Dynamics 2008; 237: 403-410.
Acharyya, S., S.A. Villalta, 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 IKK/NF-kB signaling interplay in macrophages and myofibers promotes muscle wasting in Duchenne muscular dystrophy. Journal of Clinical Investigation 2007; 117: 889-901.
Tidball, J.G. and M. Wehling-Henricks Macrophages promote muscle membrane repair and muscle fiber growth and regeneration during modified muscle loading in mice in vivo. Journal of Physiology 2007; 578.1: 327-336.
Pfister, K., J. Radons, J.G. Tidball, M. Pfeifer, L. Freitag, H-J. Feldmann, V. Milani, R. Issels and G. Multhoff Patient survival by Hsp70 membrane-phenotype: association with different routes of metastasis. Cancer 2007; 110: 926-35.
Tidball, J.G. and M.J. Spencer Skipping along to new gene therapeutics for muscular dystrophy. Nature Medicine 2003; 9: 997-998.
Chang, W., S. Iannaccone, K. Lau, B. Masters, T. McCabe K. McMillan, R. Padre, M.J. Spencer, J.G. Tidball and J.T. Stull Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. Proc. Natl. Acad. Sci. USA 1996; 93: 9142-47.
Tidball, JG Wehling-Henricks, M Damage and inflammation in muscular dystrophy: potential implications and relationships with autoimmune myositis. Current Opinion in Rheumatology. 2005; 17(6): 707-13.
Wehling-Henricks, M Jordan, MC Roos, KP Deng, B Tidball, JG Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium. Human Molecular Genetics. 2005; 14(14): 1921-33.
Nguyen, HX Lusis, AJ Tidball, JG Null mutation of myeloperoxidase in mice prevents mechanical activation of neutrophil lysis of muscle cell membranes in vitro and in vivo. Journal of Physiology. 2005; 565(Pt 2): 403-13.
Tidball, JG Inflammatory processes in muscle injury and repair. American Journal of Physiology. 2005; 288(2): R345-53.
Tidball, JG Wehling-Henricks, M Evolving therapeutic strategies for Duchenne muscular dystrophy: targeting downstream events. Pediatric Research. 2004; 56(6): 831-41.
Shiao, T Fond, A Deng, B Wehling-Henricks, M Adams, ME Froehner, SC Tidball, JG 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 beta1-syntrophins. Human Molecular Genetics. 2004; 13(17): 1873-84.
Wehling-Henricks, M Lee, JJ Tidball, JG Prednisolone decreases cellular adhesion molecules required for inflammatory cell infiltration in dystrophin-deficient skeletal muscle. Neuromuscular Disorders. 2004; 14(8-9): 483-90.
Tidball, JG Wehling-Henricks, M 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. 2004; 82(4): 312-20.
Kramerova, I Kudryashova, E Tidball, JG Spencer, MJ Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro. Human Molecular Genetics. 2004; 13(13): 1373-88.
Nguyen, HX Tidball, JG Null mutation of gp91phox reduces muscle membrane lysis during muscle inflammation in mice. Journal of Physiology. 2003; 553(Pt 3): 833-41.
Nguyen, HX Tidball, JG Expression of a muscle-specific, nitric oxide synthase transgene prevents muscle membrane injury and reduces muscle inflammation during modified muscle use in mice. Journal of Physiology. 2003; 550(Pt 2): 347-56.
Nguyen, HX Tidball, JG Interactions between neutrophils and macrophages promote macrophage killing of rat muscle cells in vitro. Journal of Physiology. 2003; 547(Pt 1): 125-32.
Tidball, J.G. and Spencer, M. Expression of a calpastatin transgene slows muscle wasting and obviates changes in myosin isoform expression during murine muscle disuse. Journal of Physiology. 2002; 545(Pt 3): 819-28.
Tidball, JG Interactions between muscle and the immune system during modified musculoskeletal loading. Clinical Orthopaedics and Related Research. 2002; 403S(403 Suppl): S100-9.
Wehling, M., Spencer, M. and J.G. Tidball A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice. Journal of Cell Biology. 2001; 155(1): 123-31.
Spencer, MJ Tidball, JG Do immune cells promote the pathology of dystrophin-deficient myopathies?. Neuromuscular Disorders. 2001; 11(6-7): 556-64.
Spencer, MJ Montecino-Rodriguez, E Dorshkind, K Tidball, JG Helper (CD4(+)) and cytotoxic (CD8(+)) T cells promote the pathology of dystrophin-deficient muscle. Clinical Immunology . 2001; 98(2): 235-43.
Koh, TJ Tidball, JG Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle cells. American Journal of Physiology. 2000; 279(3): C806-12.
Frenette, J Cai, B Tidball, JG Complement activation promotes muscle inflammation during modified muscle use. American Journal of Pathology. 2000; 156(6): 2103-10.
Zhu, X Hadhazy, M Wehling, M Tidball, JG McNally, EM Dominant negative myostatin produces hypertrophy without hyperplasia in muscle. FEBS Letters. 2000; 474(1): 71-5.
Cai, B Spencer, MJ Nakamura, G Tseng-Ong, L Tidball, JG Eosinophilia of dystrophin-deficient muscle is promoted by perforin-mediated cytotoxicity by T cell effectors. American Journal of Pathology. 2000; 156(5): 1789-96.
Tidball, JG Spencer, MJ Calpains and muscular dystrophies. International Journal of Biochemistry & Cell Biology. 2000; 32(1): 1-5.
Wehling, M Cai, B Tidball, JG Modulation of myostatin expression during modified muscle use. FASEB Journal. 2000; 14(1): 103-10.
Tidball, JG Spencer, MJ Wehling, M Lavergne, E Nitric-oxide synthase is a mechanical signal transducer that modulates talin and vinculin expression. Journal of Biological Chemistry . 1999; 274(46): 33155-60.
Koh, TJ Tidball, JG Nitric oxide synthase inhibitors reduce sarcomere addition in rat skeletal muscle. Journal of Physiology. 1999; 519 Pt 1: 189-96.
Tidball, JG Lavergne, E Lau, KS Spencer, MJ Stull, JT Wehling, M Mechanical loading regulates NOS expression and activity in developing and adult skeletal muscle. American Journal of Physiology. 1998; 275(1 Pt 1): C260-6.
Spencer, MJ Walsh, CM Dorshkind, KA Rodriguez, EM Tidball, JG Myonuclear apoptosis in dystrophic mdx muscle occurs by perforin-mediated cytotoxicity. Journal of Clinical Investigation. 1997; 99(11): 2745-51.
Albrecht, DE Tidball, JG Platelet-derived growth factor-stimulated secretion of basement membrane proteins by skeletal muscle occurs by tyrosine kinase-dependent and -independent pathways. Journal of Biological Chemistry. 1997; 272(4): 2236-44.
Wehling-Henricks, M. and J.G. Tidball Neuronal nitric oxide synthase-rescue of dystrophin/utrophin double knockout mice does not require nNOS localization to the cell membrane. PLoS One 2011; 6: e25071.
Sakellariou, G.K., Pye, D., Vasilaki, A., Zibrik, L., Palomero, J., Kabayo, T., McArdle, F., Van Remmen, H., Richardson, A., Tidball, J.G., McArdle, A. and M. J. Jackson Role of superoxide-nitric oxide interactions in the accelerated age-related loss of muscle mass in mice lacking Cu,Zn superoxide dismutase. Aging Cell 2011; 10: 749-760.
Villalta, S.A., Deng, B., Rinaldi, C., Wehling-Henricks, M. and J. G. Tidball IFNγ promotes muscle damage in the mdx mouse model of Duchenne muscular dystrophy by suppressing M2 macrophage activation and inhibiting muscle cell proliferation. J. Immunol 2011; 187: 5419-5428 .