Research Interests:

Dr. Spencer's research focuses on the pathogenesis of muscular dystrophy. The lab uses a multidisciplinary approach that ranges from the generation of genetically modified mice to the use of biochemical, cell biological, immunological and functional approaches. She has had a career long interest in pathogenesis of muscular dystrophy (DMD and LGMD) and has extensive experience in generating and phenotyping genetically modified mouse models (transgenic, knock out and knock in models). Her more recent work has examined the immunological contribution to fibrotic processes in muscular dystrophy. Currently, Dr. Spencer is a co-director of the Center for Duchenne Muscular Dystrophy at UCLA, along with Drs. Carrie Miceli and Stanley Nelson (see the Center Website http://www.cdmd.ucla.edu). The goals of this Center are to facilitate Translational Studies in muscle disease through the availability of basic science cores, a seminar series, pilot and feasibility funds and through the creation of a multidisciplinary clinic. The Center Investigators use highthroughput screening approaches to identify drugs that slow the pace of muscular dystrophy. Recently, Dr. Spencer has partnered with Drs. Miceli and Nelson to identify a drug to improve the efficiency of exon skipping, which is currently a type of therapy in clinical trials for DMD. This effort led to the awarding of a Challenge Grant from the Office of the Director at the NIH. A particular strength of the Spencer lab is the longitudinal and multidisciplinary approach used to study these muscular dystrophies. One of these studies was carried into clinical trials, in which Dr. Spencer was the principal investigator. The Spencer lab welcomes any students or post-docs who are interested in Translational Studies in the Muscular Dystrophies.


Kramerova, I., Kudryashova, E., Saez, A., Lopez de Munain, A., Ermolova, N., and Spencer, M. J. (2012). Impaired calcium calmodulin kinase signaling and muscle adaptation response in the absence of calpain 3 Human Molecular Genetics 21(14): 3193-3204

Kudryashova, E., Kramerova, I., and Spencer. M. J. (2012). Satellite cell senescence underlies the myopathy in a mouse model of limb girdle muscular dystrophy 2H Journal of Clinical Investigation 122(5): 1764-1776

Kendall, GC, Mokhonova, E.I, Moran, M., Sejbuk, N.E., Wang, D.W., Silva, O., Wang, R.T. Martinez, L. Lu, Q.L., Damoiseaux, R., Spencer, M.J., Nelson, S.N. and Miceli, M.C. (2012). Dantrolene enhances antisense-medicated exon skipping in human and mouse models of Duchenne muscular dystrophy Science Translational Medicine 4(166): 164-ra160

Kudryashova, E., Stryk, A., Cannon, S. C., and Spencer, M. J. (2011). The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype Human Molecular Genetics 20(20): 3925-3932

Ermolova, N., Kudryashova,E., DiFranco, M., Vergara, J., Kramerova,I., and Spencer, M. J. (2011). Pathogenity of some limb girdle muscular dystrophy mutations can result from reduced anchorage to myofibrils and altered stability of calpain 3 Human Molecular Genetics 20(17): 3331-3345

Kramerova I, Kudryashova E, Wu B, Germain S, Vandenborne K, Romain N, Haller R, Verity MA, Spencer MJ (2009). Mitochondrial abnormalities, energy deficit and oxidative stress are features of calpain 3 deficiency in skeletal muscle Hum Mol Genet 1:18: 3194-3205

Vetrone, SA., Montecino-Rodriguez, E., Kudryashova, E., Kramerova, I., Hoffman, EP., Liu, SD., Miceli, M.C and Spencer, MJ (2009). Osteopontin Promotes Fibrosis in Mdx Muscle Through Modulation of Immune Cell Subsets and Intramuscular TGFbeta J of Clinical Investigation 119: 1583-1594

Kudryashova E, Wu J, Havton, L. and Spencer MJ. (2009). Deficiency of the E3 ubiquitin ligase Trim32 in mice leads to a myopathy with a neurogenic component Hum Mol Genet 18: 1353-1367

Kramerova I, Kudryashova E, Wu B, Ottenheijm C, Granzier H, Spencer MJ (2008). Novel role of calpain-3 in the triad-associated protein complex regulating calcium release in skeletal muscle Hum Mol Genet 1:17: 3271-3280

Skura, C.L., Fowler, E.G.,Wetzel, G.T., Graves, M.G. and Spencer, M.J. (2008). Albuterol Increases Lean Body Mass in Ambulatory Boys with Duchenne or Becker Muscular Dystrophy Neurology 70: 137-143

Groshong JS, Spencer MJ, Bhattacharyya BJ, Kudryashova E, Vohra BP, Zayas R, Wollmann RL, Miller RJ, Gomez CM (2007). Calpain activation impairs neuromuscular transmission in a mouse model of the slow-channel myasthenic syndrome J Clin Invest 117: 2903-2912

Cohen, N, Kudryashova, E, Kramerova, I, Anderson,L.V.B. Beckmann, J.S., Bushby, KM and Spencer, M.J. (2006). Identification of putative in vivo substrates of calpain 3 by comparative proteomics of over-expressing transgenic and non-transgenic mice Proteomics 6: 6075-6084

Kramerova, I., Kudryashova, E. and Spencer, M.J (2006). Regulation of M-cadherin-b-catenin complex by calpain 3 during terminal stages of myogenic differentiation Molecular Cellular Biology 26: 8437-8447

Kudryashova, E. Kudryashov, D., Kramerova, I. and M.J. Spencer (2005). Trim32 is a Ubiquitin Ligase Mutated in Limb Girdle Muscular Dystrophy Type 2H That Binds to Skeletal Muscle Myosin and Ubiquitinates Actin Journal of Molecular Biology 25: 413-424

Huebsch, K.A., Kudryashova, E., Wooley, C.M., Sher, R.B., Seburn, K.L., Spencer, M.J. and G.C. Cox. (2005). Mdm muscular dystrophy is not a result of aberrant CAPN3 activation but reveals a novel functional role for titin's N2A domain Human Molecular Genetics 14: 2801-2811

Kramerova, I. Kudryashova, E. and M.J. Spencer (2005). Calpain 3 is involved in sarcomere remodeling in vivo by promoting ubiquitination of muscle proteins Human Molecular Genetics 14: 2125-2134

Kramerova, I, Kudryashova, E., Tidball, J.G. and M.J. Spencer (2004). Null mutation of calpain 3 in mice causes abnormal sarcomere formation in vivo and in vitro Human Molecular Genetics 13(13): -

Fowler, E.G., Graves, M.C., Wetzel, G.T. and Spencer, M.J. (2004). Pilot Trial of Albuterol in Duchenne and Becker Muscular Dystrophy Neurology March 62: 1006-1008

Guyon, J.R. Kudryashova, E., Potts, A., Dalkilic, I., Brosius, M., Thompson, T.G., Beckmann, J.S., Kunkel, L.M. and Spencer, M.J. (2003). Calpain 3 cleaves Filamin C and Regulates its Ability to Interact With Gamma and Delta Sarcoglycans Muscle and Nerve 28: 472-483

Tidball, J.G. and Spencer, M.J. (2003). Skipping to new gene therapies for muscular dystrophy Nature Medicine 9(8): 997-998

Spencer, M.J. and Mellgren, R.L. (2002). Overexpression of a calpastatin transgene in mdx muscle reduces dystrophic pathology Human Molecular Genetics 11(21): 2645-2655

Tidball, J.G. and Spencer, M.J. (2002). Expression of a calpastatin transgene slows muscle wasting and obviates changes in myosin isoform expression during mouse muscle disuse Journal of Physiology Dec 15 545 (Pt 3): 819-828

Spencer, M.J., Guyon, J.R., Sorimachi, H., Potts, A., Richard, I., Herasse, M., Chamberlain, J., Dalkilic, I., Kunkel, L.M., and Beckmann, J.S. (2002). Stable expression of calpain 3 from a muscle transgene in vivo; immature muscle in transgenic mice suggests a role for calpain 3 in muscle maturation Proceedings of the National Academy of Sciences 99(3): 8874-8879

Wehling, M., Spencer, M.J. and Tidball, J.G. (2001). A nitric oxide synthase transgene ameliorates muscular dystrophy in the mdx mouse Journal of Cell Biology 155(1): 1-10

Spencer, M.J. and Tidball, J.G. (2001). Do immune cells promote the pathology of dystrophin-deficient myopathies? Neuromuscular Disorders 11(6-7): 556-564

Spencer, M.J., Montecino Rodriguez, E., Dorshkind, K. and Tidball, J.G. (2001). CD4+ (helper) and CD8+ (cytotoxic) T cells promote the pathology of dystrophin-deficient muscle Clinical Immunology 98(2): 235-243

Spencer, M.J., Marino, M. and Winckler, W. (2000). Altered pathological progression of diaphragm and quadriceps muscles in TNF-deficient, dystrophin-deficient mice Neuromuscular Disorders 10(8): 612-619

Spencer, M.J., Walsh, C.M., Dorshkind, K.A., Montecino-Rodriguez, E. and Tidball, J.G. (1997). Myonuclear apoptosis in dystrophin-deficient muscle occurs by perforin-mediated cytotoxicity The Journal of Clinical Investigation 99(11): 2745-2751

Spencer, M.J., Tidball, J.G., Anderson, L.V.B., Bushby, J., Harris, J., Passos-Bueno, R.M., Somer, H., Vainzof, M. and Zatz, M. (1997). Absence of calpain III in a form of limb-girdle muscular dystrophy Journal of the Neurological Sciences 146: 173-178

Tidball, J.G., Albrecht, D.E., Lokensgard, B.E. and Spencer, M.J. (1995). Apoptosis precedes necrosis of dystrophin-deficient muscle Journal of Cell Science 108(6): 2197-2204

Spencer, M.J., Croall, D.E. and Tidball, J.G. (1995). Calpains are activated in necrotic fibers from mdx dystrophic mice Journal of Biological Chemistry 270(18): 10909-10914