email: jtidball@physci.ucla.eduResearch 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.
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
Kyckelhahn, B.A., P.B. Nason, J.G. Tidball J.G, and A.M. Boriek. (2003). Kinematic modeling of single muscle fiber during diaphragm shortening J. Biomech 36: 457-461
Nguyen, H.X. and J.G. Tidball. (2003). Expression of a muscle-specific, nitric oxide synthase transgene prevents muscle membrane injury and reduces muscle inflammation during modified muscle use J. Physiol. (Lond) 550: 347-356
Nguyen, H.X. and J.G. Tidball. (2003). Interactions between neutrophils and macrophages promote macrophage killing of muscle cells in vitro J. Physiol. (Lond) 547: 125-132
Cheung, E.V. and J.G. Tidball. (2003). Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use Inflam. Res 52: 170-176
Tidball, J.G. and M.J. Spencer. (2003). Skipping to new gene therapies for muscular dystrophy Nature Medicine 9: 997-998
Tidball, J.G. and M.J.Spencer. (2002). Expression of a calpastatin transgene slows muscle wasting and obviates changes in myosin isoform expression during mouse muscle disuse J. Physiol. (Lond) 545: 819-828
Tidball, J.G. (2002). Interactions between muscle and the immune system during modified musculoskeletal loading Clinical Orthop 400S: 100-109
Spencer, M.J., E. Montecino-Rodriguez, K. Dorshkind and J.G. Tidball. (2001). Helper (CD4+) and cytotoxic (CD8+) T cells promote the pathology of dystrophin-deficient muscle Clinical Immunology 98: 235-243
Wehling, M., M.J. Spencer, and J.G. Tidball. (2001). A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice J. Cell Biol 155: 123-132
Spencer, M.J. and J.G. Tidball. (2001). Do immune cells promote the pathology of dystrophin-deficient myopathies? Neuromuscular Disorders 11: 556-564
Tidball, J.G. and M.J. Spencer. (2000). Calpains and muscular dystrophies Int. J. Biochem. Cell Biol 32: 1-5
Cai, B., M. J. Spencer, G. Nakamura, L. Tseng-Ong and J.G. Tidball. (2000). Eosinophilia of dystrophin-deficient muscle is promoted by perforin-mediated cytotoxicity by T-cell effectors Amer. J. Pathol 156: 1789-1796
Wehling, M., B. Cai and J.G. Tidball. (2000). Modulation of myostatin expression during modified muscle use FASEB J 14: 103-110
Frenette, J., B. Cai and J.G. Tidball. (2000). Complement activation promotes muscle inflammation during modified muscle use Amer. J. Pathol 156: 2103-2110
Zhu, X., M. Hadhazy, M. Wehling, J.G. Tidball and E.M McNally. (2000). Dominant negative myostatin produces hypertrophy without hyperplasia in muscle FEBS Lttrs 474: 71-75
Koh, T.J. and J.G. Tidball. (2000). Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle cells Amer. J. Physiol. (Cell Physiol.) 279: 806-812
Boriek, A.M., Y. Capetanaki, W. Hwang, T. Officer, M. Badshah, J. Rodarte and J. G. Tidball. (2000). Desmin integrates the three-dimensional mechanical properties of skeletal muscle Amer. J. Physiol. (Cell Physiol.) 280: C46-52
Tidball, J. G. M. J. Spencer, M. Wehling and E. Lavergne. (1999). Nitric oxide synthase is a mechanical signal transducer that modulates talin and vinculin expression J. Biol. Chem 27: 33155-33160
Koh, T.J. and J.G. Tidball. (1999). Nitric oxide synthase inhibitors reduce sarcomere addition in rat skeletal muscle J. Physiol. (Lond) 519: 189-196
Tidball, J.G., E. Berchenko and J. Frenette. (1999). Macrophage invasion does not contribute to muscle membrane injury during inflammation J. Leukocyte Biol 65: 492-498
Tidball, J.G., E. Lavergne, K. S. Lau, M. J. Spencer, J. T. Stull and M. Wehling. (1998). Mechanical loading regulates nitric oxide synthase expression and activity in developing and adult skeletal muscle Amer. J. Physiol. (Cell Physiol.) 275: 260-266
Frenette, J. and J.G. Tidball. (1998). Mechanical loading regulates the expression of talin and its mRNA which are concentrated at myotendinous junctions Amer. J. Physiol. (Cell Physiol.) 275: 818-825
Pizza, F. X., I. Hernandez and J.G. Tidball. (1998). Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use J. Leukocyte Biol 64: 427-433
Wehling, M., J.T. Stull, T.J. McCabe and J.G. Tidball. (1998). Sparing of mdx extraocular muscles from dystrophic pathology is not attributable to normalized concentration or distribution of neuronal nitric oxide synthase Neuromuscular Disorders 8: 22-29
Tidball, J.G. and D.A. Albrecht (1998). Regulation of apoptosis by cellular interactions with the extracellular matrix In: When Cells Die: A Comprehesive Evaluation of Apoptosis and Programmed Cell Death 411-427
Spencer, M.J., C.M. Walsh, K.A. Dorshkind, E. Montecino-Rodriguez and J.G. Tidball. (1997). Myonuclear apoptosis in dystrophic mdx muscle occurs by perforin-mediated cytotoxicity J. Clin. Invest 99: 2745-2751
Albrecht, D.A. and J.G. Tidball (1997). PDGF stimulated secretion of basement membrane proteins by skeletal muscle occurs by tyrosine kinase dependent and independent pathways J. Biol. Chem 272: 2236-2244
Tidball, J.G. and T.L. Daniel. (1996). Myotendinous junctions of tonic muscle cells: Structure and loading Cell. Tissue Res 245: 315-322
Tidball, J.G. and B.A. St. Pierre (1996). Apoptosis of macrophages during the resolution of muscle inflammation J. Leukocyte Biol 59: 380-388
Spencer, M.J. and J.G. Tidball. (1996). Calpain translocation during muscle fiber necrosis and regeneration in dystrophin-deficient mice Exper. Cell Res 226: 264-272
Chang, W-J., S.T. Iannaccone, K.S. Lau, B.S.S. Masters, T.J. McCabe, K. McMillan, R.C. Padre, M.J. Spencer, J.G. Tidball and J.T. Stull (1996). Neuronal nitric oxide synthase and systrophin-deficient muscular dystrophy Proc. Natl. Acad. Sci., USA 93: 9142-9147
Spencer, M.J., J.G. Tidball, L.V.B. Anderson, K.M.D. Bushby, J.B. Harris, M.R. Passos-Bueno, H. Somer, H. Vainzof and M. Zatz (1996). Absence of calpain 3 in a form of limb-girdle muscular dystrophy (LGMD2A) J. Neurol. Sci 146: 173-178
Spencer, M.J., B. Lu and J. G. Tidball (1996). Calpain II expression is increased by changes in mechanical loading of muscle in vivo J. Cell Biochem 64: 55-56
Murray, E.J.B., K. K-T. Tram, M.J. Spencer, J.G. Tidball, S.S Murray and D.B.N. Lee (1995). PTH-mediated osteoblast retraction: possible participation of the calpain pathway Miner. Electrolyte Metab 21: 184-188
Tidball, J.G. (1995). Inflammatory cell response to acute muscle injury Med. Sci. Sports Exer 27: 1022-1032
Tidball, J.G., D.E. Albrecht, B.E. (1995). Lokensgard and M.J. Spencer. 1995. Apoptosis precedes necrosis of dystrophin-deficient muscle J. Cell Sci 108: 2197-2204
Spencer, M.J., D.E. Croall and J.G. Tidball. (1995). Calpains are activated in necrotic fibers from mdx dystrophic mice J. Biol. Chem 270: 10909-10914
Law, D.J., A. Caputo and J.G. Tidball (1995). Site and mechanics of failure in normal and dystrophin-deficient Skeletal muscle Muscle & Nerve 18: 216-223
Tidball, J.G. (1994). Assembly of myotendinous junctions in the chick embryo: Deposition of P68 is an early event in myotendinous junction formation Devel. Biol 163: 447-456
Law, D.J., D.L. Allen and J.G. Tidball. (1994). Talin, vinculin, and DRP (utrophin) concentrations are increased at mdx myotendinous junctions following onset of necrosis J. Cell Sci 107: 1477-1483
St. Pierre, B.A. and J.G. Tidball. (1994). Differential response of macrophage subpopulations to soleus muscle reloading after rat hindlimb suspension J. Appl. Physiol 77: 290-297
St. Pierre, B.A. and J.G. Tidball. (1994). Macrophage activation and muscle remodeling at myotendinous junctions following modifications in muscle loading Amer. J. Pathol 145: 1463-1471
Ridge, J.C., J.G. Tidball, K. Ahl, D.J. Law and W.L. Rickoll. (1994). Modifications in myotendinous junction surface morphology in dystrophin-deficient mouse muscle Exp. Molec. Pathol 61: 58-68
Tidball, J.G. and M.J. Spencer. (1993). PDGF stimulation induces phosphorylation of talin and cytoskeletal reorganization in skeletal muscle J. Cell Biol 123: 627-636
Tram, K., M. Spencer, S.S. Murray, D.B.N. Lee, J.G. Tidball and E.J.B. Murray. (1993). Identification of calcium-activated neutral protease activity and its regulation by parathyroid hormone in mouse osteoblastic cells Biochem. Molec. Biol. Internat 29: 981-987
Law, D.J. and J.G. Tidball (1993). Dystrophin deficiency is associated with myotendinous junction defects in prenecrotic and fully regenerated skeletal muscle Amer. J. Pathol 142: 1513-1523
Tidball, J.G., G. Salem and R. Zernicke (1993). Site and mechanical conditions for failure of skeletal muscle in experimental strain injuries J. Appl. Physiol 74: 1280-1286
Tidball, J.G. (1992). Distribution of collagens and fibronectin in the subepicardium during avian cardiac development Anat. Embryol 185: 155-162
Tidball, J.G., L. Latus and J. Weckerle. (1992). Developmental modulation of embryonic cardiac myocyte adhesion to cardiac collagens in vitro Exp. Cell Res 199: 341-348
Tidball, J.G. (1992). Desmin at myotendinous junctions Exp. Cell Res 199: 206-212
Tidball, J.G. and D.M. Quan. (1992). Reduction in myotendinous junction surface area in plantaris muscle of rats subjected to four-day spaceflight J. Appl. Physiol 73: 59-64
Tidball, J.G. and D.M. Quan. (1992). Modifications in myotendinous junction structure following denervation Acta Neuropath 84: 135-140
Law, D.J. and J.G. Tidball. (1992). Identification of a putative collagen-binding protein from chicken skeletal muscle as glycogen phosphorylase Biochem. Biophys. Acta 1122: 225-233
Spencer, M.J. and J.G. Tidball. (1992). Calpain concentration is elevated although net calcium-dependent proteolysis is suppressed in dystrophin-deficient muscle Exp. Cell Res 203: 107-114
Tidball, J.G., M.J. Spencer and B.A. St. Pierre. (1992). PDGF-receptor concentration is elevated in regenerative muscle fibers in dystrophin-deficient muscle Exp. Cell Res 203: 141-149
Tidball, J.G. (1992). Identification and distribution of a novel, collagen-binding protein in the developing subepicardium and endomysium J. Biol. Chem 267: 21211-21219
Tidball, J.G. and K.L. Andolina. (1992). Structure and protein composition of sites of papillary muscle attachment to chordae tendinae in avian hearts Cell Tissue Res 270: 527-533
Tidball, J.G. (1991). Myotendinous junction injury in relation to junction structure and molecular composition Exer. Sport Sci. Rev 19: 419-446
Tidball, J.G. (1991). Force transmission across muscle cell membranes J. Biomech 24 (Suppl.): 43-52
Tidball, J.G., J.E. Cederdahl and D.M. Bers. (1991). Quantitative analysis of regional variability in the distribution of transverse tubules in rabbit myocardium Cell Tissue Res 264: 293-298
Tidball, J.G. and D.J. Law. (1991). Dystrophin is required for normal thin filament-membrane associations at myotendinous junctions Amer. J. Pathol 138: 17-21
Tidball, J.G. Myonexin (1990). Myonexin: an 80 kD glycoprotein that binds fibronectin and is located at embryonic myotendinous junctions Devel. Biol 142: 103-114
Tidball, J.G. and C. Lin. (1989). Structural changes at the myogenic cell surface during the formation of myotendinous junctions Cell Tissue Res 257: 77-84
Tidball, J.G. and M. Chan. (1989). Adhesive strength of single muscle cells to basement membrane at myotendinous junctions J. Appl. Physiol 67: 1063-1069
S.L.-Y. Woo and J.A. Buckwalter (1988). Structure, loading and failure at muscle-tendon junctions Injury and Repair of the Musculoskeletal Soft Tissues 167-207
Tidball, J.G. (1988). Identification of an 80 kD glycoprotein at sites of close apposition between skeletal muscle cells Eur. J. Cell Biol 46: 161-167
Tidball, J.G., R. Smith, M.J. Shattock and D.M. Bers. (1988). Differences in action potential configuration in ventricular trabeculae correlate with differences in density of transverse tubule - sarcoplasmic reticulum couplings J. Molec. Cell. Cardiol 20: 539-546
Tidball, J.G. and M.V. Gadus. (1988). Cytochemical, histological and phylogenetic distribution of a 38,000-Dalton protein associated with transverse tubules J. Cell. Biochem 38: 99-112
Tidball, J.G. (1987). Alpha-actinin is absent from terminal segments of myofibrils and from subsarcolemmal densities in frog-skeletal muscle Exp. Cell Res 170: 469-482
Shattock, M.J., K.C. Warner, J.G. Tidball and D.M. Bers. (1987). Two different electro-physiological responses to ryanodine: Evidence for two populations of muscles isolated from the rabbit right ventricle J. Molec. Cell. Cardiol 19: 751-762
Tidball, J.G. and T.L. Daniel. (1986). Elastic energy storage in rigored skeletal muscle cells under physiological loading conditions Amer. J. Physiol 250R: 56-64
Tidball, J.G., T.O'Halloran and K. Burridge. (1986). Talin at myotendinous junctions J. Cell Biol 103: 1465-1472
Tidball, J.G. (1986). Energy stored and dissipated in skeletal muscle basement membranes during sinusoidal oscillations Biophys. J 50: 1127-1138
Tidball, J.G. (1985). Coelenterata: The secreted surface The Biology of the Integument. Vol. I 69-78
Tidball, J.G. (1985). Changes in skeletal chemistry and skeletogenic cell ultrastructure between young and old sites on axial skeletons Comp. Biochem. Physiol 81B: 827-831
Tidball, J.G. (1984). Myotendinous junctions: Morphological changes and mechanical failure associated with muscle cell atrophy Exp. Molec. Pathol 40: 1-12
Tidball, J.G. (1983). The geometry of actin filament-membrane associations can modify the adhesive strength at the myotendinous junction Cell Motil 3: 439-448
Tidball, J.G. (1982). An ultrastructural and cytochemical analysis of the cellular basis for the tyrosine-derived collagen crosslinks Cell Tissue Res 222: 635-645
Tidball, J.G. (1982). Fine structural aspects of anthozoan desmocyte development Tissue and Cell 14: 85-96
Ball, A.K., J.G. Tidball and D.H. Dickson. (1981). An alternative to the flat substrate method of preparing electron microscope autoradiographs Stain Technol 56: 239-245
Tidball, J.G. (1981). Lipoprotein secretion during the formation of the axial skeleton of Leptogorgia virgulata (Cnidaria: Gorgonacea) Cell Tissue Res 219: 327-338
Brenchley, G.A. and J.G. Tidball. (1980). Tube-cap orientations of Diopatra cuprea (Bosc.) (Polychaeta): The compromise between physiology and foraging Mar. Behav. Physiol 7: 1-13
Tidball, J.G. (1980). The fine structure of the "gorgonin" secreting cells of the gorgonian coral Leptogorgia virgulata Developmental and Cellular Biology of Coelenterates 197-202