Melissa J. Spencer, Ph.D.

Office Address:
635 Charles Young Dr. So
mail code 703422
Los Angeles, CA 90095

Work Address:
635 Charles E. Young Dr. So
mail code 733422
Los Angeles, CA 90095

Professor, Neurology
Research Interests
The Spencer lab is focused on understanding mechanisms and identifying treatments for the genetically inherited muscular dystrophies.

Dr. Melissa Spencer is Professor of Neurology and Neuromuscular Program Director in the UCLA David Geffen School of Medicine. She obtained her PhD from UCLA and established her independent lab in 1999. Her lab utilizes advanced genetic engineering technology to develop new treatments for Duchenne muscular dystrophy and limb girdle muscular dystrophy.  These approaches include CRISPR based gene editing platforms as well as gene replacement therapies.  The lab is interested in both non-viral and viral delivery approaches for delivering these therapies. In collaboration with Drs. Courtney Young and April Pyle, they developed a CRISPR based therapy that is being translated through their startup MyoGene Bio. The Spencer lab is also interested in defining how the immune system promotes muscular dystrophy and as a separate line of inquiry, how immune cells respond to AAV exposure. Understanding this interaction can lead to new therapeutic targets to improve the safety and efficacy of gene therapies that rely on AAV as a delivery vehicle. Dr. Spencer serves on the Scientific Advisory Committee for the Muscular Dystrophy Association, Parent Project Muscular Dystrophy and the Coalition to Cure Calpain 3.  She was awarded a Presidential Early Career Award for Scientists and Engineers (PECASE) in 2001.




A selected list of publications:

Young Courtney S, Hicks Michael R, Ermolova Natalia V, Nakano Haruko, Jan Majib, Younesi Shahab, Karumbayaram Saravanan, Kumagai-Cresse Chino, Wang Derek, Zack Jerome A, Kohn Donald B, Nakano Atsushi, Nelson Stanley F, Miceli M Carrie, Spencer Melissa J, Pyle April D   A Single CRISPR-Cas9 Deletion Strategy that Targets the Majority of DMD Patients Restores Dystrophin Function in hiPSC-Derived Muscle Cells Cell stem cell, 2016; .
Villalta SA, Rosenthal W, Martinez L, Kaur A, Sparwasser T, Tidball JG, Margeta M, Spencer MJ, Bluestone JA.   Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy, Science Translational Medicine, ; 6(258): .
Martinez Leonel, Ermolova Natalia V, Ishikawa Tomo-O, Stout David B, Herschman Harvey R, Spencer Melissa J   A reporter mouse for optical imaging of inflammation in mdx muscles Skeletal muscle, 2015; 5(2): 15.
Ermolova NV, Martinez L, Vetrone SA, Jordan MC, Roos KP, Sweeney HL, Spencer MJ.   Long-term administration of the TNF blocking drug Remicade (cV1q) to mdx mice reduces skeletal and cardiac muscle fibrosis, but negatively impacts cardiac function, Neuromuscular Disorders, 2014; 24(7): 583-595.
Ermolova Natalia, Kramerova Irina, Spencer Melissa J   Autolytic activation of calpain 3 proteinase is facilitated by calmodulin protein The Journal of biological chemistry, 2015; 290(2): 996-1004.
Kendall Genevieve C, Mokhonova Ekaterina I, Moran Miriana, Sejbuk Natalia E, Wang Derek W, Silva Oscar, Wang Richard T, Martinez Leonel, Lu Qi L, Damoiseaux Robert, Spencer Melissa J, Nelson Stanley F, Miceli M Carrie   Dantrolene enhances antisense-mediated exon skipping in human and mouse models of duchenne muscular dystrophy Science translational medicine, 2012; 4(164): 164ra160.
Kramerova I, Kudryashova E, Ermolova N, Saenz A, Jaka O, Lopez de Munain A, Spencer M J   Impaired calcium calmodulin kinase signaling and muscle adaptation response in the absence of calpain 3 Human molecular genetics, 2012; 21(14): 3193-204.
Kudryashova Elena, Kramerova Irina, Spencer Melissa J   Satellite cell senescence underlies myopathy in a mouse model of limb-girdle muscular dystrophy 2H The Journal of clinical investigation, 2012; 122(5): 1764-76.
Ermolova Natalia, Kudryashova Elena, DiFranco Marino, Vergara Julio, Kramerova Irina, Spencer Melissa J   Pathogenity of some limb girdle muscular dystrophy mutations can result from reduced anchorage to myofibrils and altered stability of calpain 3 Human molecular genetics, 2011; 20(17): 3331-45.
Kudryashova Elena, Struyk Arie, Mokhonova Ekaterina, Cannon Stephen C, Spencer Melissa J   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, 2011; 20(20): 3925-32.
Kudryashova Elena, Wu Jun, Havton Leif A, Spencer Melissa J   Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component Human molecular genetics, 2009; 18(7): 1353-67.
Nelson Stanley F, Crosbie Rachelle H, Miceli M Carrie, Spencer Melissa J   Emerging genetic therapies to treat Duchenne muscular dystrophy Current opinion in neurology, 2009; 22(5): 532-8.
Kramerova Irina, Kudryashova Elena, Wu Benjamin, Germain Sean, Vandenborne Krista, Romain Nadine, Haller Ronald G, Verity M Anthony, Spencer Melissa J   Mitochondrial abnormalities, energy deficit and oxidative stress are features of calpain 3 deficiency in skeletal muscle Human molecular genetics, 2009; 18(17): 3194-205.
Vetrone Sylvia A, Montecino-Rodriguez Encarnacion, Kudryashova Elena, Kramerova Irina, Hoffman Eric P, Liu Scot D, Miceli M Carrie, Spencer Melissa J   Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-beta The Journal of clinical investigation, 2009; 119(6): 1583-94.
Skura, C. L. Fowler, E. G. Wetzel, G. T. Graves, M. Spencer, M. J.   Albuterol increases lean body mass in ambulatory boys with Duchenne or Becker muscular dystrophy Neurology, 2008; 70(2): 137-43.
Beckmann Jacques S, Spencer Melissa   Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance Neuromuscular disorders : NMD, 2008; 18(12): 913-21.
Kramerova Irina, Kudryashova Elena, Wu Benjamin, Ottenheijm Coen, Granzier Henk, Spencer Melissa J   Novel role of calpain-3 in the triad-associated protein complex regulating calcium release in skeletal muscle Human molecular genetics, 2008; 17(21): 3271-80.
Groshong Jason S, Spencer Melissa J, Bhattacharyya Bula J, Kudryashova Elena, Vohra Bhupinder P S, Zayas Roberto, Wollmann Robert L, Miller Richard J, Gomez Christopher M   Calpain activation impairs neuromuscular transmission in a mouse model of the slow-channel myasthenic syndrome The Journal of clinical investigation, 2007; 117(10): 2903-12.
Kramerova Irina, Beckmann Jacques S, Spencer Melissa J   Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A) Biochimica et biophysica acta, 2007; 1772(2): 128-44.
Cohen Niaz, Kudryashova Elena, Kramerova Irina, Anderson Louise V B, Beckmann Jacques S, Bushby Katherine, Spencer Melissa J   Identification of putative in vivo substrates of calpain 3 by comparative proteomics of overexpressing transgenic and nontransgenic mice Proteomics, 2006; 6(22): 6075-84.
Kramerova Irina, Kudryashova Elena, Wu Benjamin, Spencer Melissa J   Regulation of the M-cadherin-beta-catenin complex by calpain 3 during terminal stages of myogenic differentiation Molecular and cellular biology, 2006; 26(22): 8437-47.
Nazarian Ramin, Starcevic Marta, Spencer Melissa J, Dell'Angelica Esteban C   Reinvestigation of the dysbindin subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1) as a dystrobrevin-binding protein The Biochemical journal, 2006; 395(3): 587-98.
Kramerova Irina, Kudryashova Elena, Venkatraman Gayathri, Spencer Melissa J   Calpain 3 participates in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway Human molecular genetics, 2005; 14(15): 2125-34.
Huebsch Kimberly A, Kudryashova Elena, Wooley Christine M, Sher Roger B, Seburn Kevin L, Spencer Melissa J, Cox Gregory A   Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain Human molecular genetics, 2005; 14(19): 2801-11.
Kudryashova Elena, Kudryashov Dmitri, Kramerova Irina, Spencer Melissa J   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, 2005; 354(2): 413-24.
Kramerova I, Kudryashova E, Tidball J G, Spencer Melissa J   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.
Fowler, EG Graves, MC Wetzel, GT Spencer, MJ   Pilot trial of albuterol in Duchenne and Becker muscular dystrophy Neurology. , 2004; 62(6): 1006-8.
Hodgetts Stuart I, Spencer Melissa J, Grounds Miranda D   A role for natural killer cells in the rapid death of cultured donor myoblasts after transplantation Transplantation, 2003; 75(6): 863-71.
Guyon Jeffrey R, Kudryashova Elena, Potts Alexandra, Dalkilic Isin, Brosius Melissa A, Thompson Terri G, Beckmann Jacques S, Kunkel Louis M, Spencer Melissa J   Calpain 3 cleaves filamin C and regulates its ability to interact with gamma- and delta-sarcoglycans Muscle & nerve, 2003; 28(4): 472-83.
Tidball James G, Spencer Melissa J   Skipping to new gene therapies for muscular dystrophy Nature medicine, 2003; 9(8): 997-8.
Gosselin Luc E, Barkley Jacob E, Spencer Melissa J, McCormick Kathleen M, Farkas Gaspar A   Ventilatory dysfunction in mdx mice: impact of tumor necrosis factor-alpha deletion Muscle & nerve, 2003; 28(3): 336-43.
Tidball James G, Spencer Melissa J   Expression of a calpastatin transgene slows muscle wasting and obviates changes in myosin isoform expression during murine muscle disuse The Journal of physiology, 2002; 545(Pt 3): 819-28.
Spencer Melissa J, Mellgren Ronald L   Overexpression of a calpastatin transgene in mdx muscle reduces dystrophic pathology Human molecular genetics, 2002; 11(21): 2645-55.
Capote Joana, Kramerova Irina, Martinez Leonel, Vetrone Sylvia, Barton Elisabeth R, Sweeney H Lee, Miceli M Carrie, Spencer Melissa J   Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotype The Journal of cell biology, 2016; 213(2): 275-88.
Xi Haibin, Langerman Justin, Sabri Shan, Chien Peggie, Young Courtney S, Younesi Shahab, Hicks Michael, Gonzalez Karen, Fujiwara Wakana, Marzi Julia, Liebscher Simone, Spencer Melissa, Van Handel Ben, Evseenko Denis, Schenke-Layland Katja, Plath Kathrin, Pyle April D   A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells Cell stem cell, 2020; .
Jaka Oihane, Kramerova Irina, Azpitarte Margarita, López de Munain Adolfo, Spencer Melissa, Sáenz Amets   C3KO mouse expression analysis: downregulation of the muscular dystrophy Ky protein and alterations in muscle aging Neurogenetics, 2012; 13(4): 347-57.
Young Courtney S, Pyle April D, Spencer Melissa J   CRISPR for Neuromuscular Disorders: Gene Editing and Beyond Physiology (Bethesda, Md.), 2019; 34(5): 341-353.
Kramerova Irina, Kumagai-Cresse Chino, Ermolova Natalia, Mokhonova Ekaterina, Marinov Masha, Capote Joana, Becerra Diana, Quattrocelli Mattia, Crosbie Rachelle H, Welch Ellen, McNally Elizabeth M, Spencer Melissa J   Spp1 (osteopontin) promotes TGFβ processing in fibroblasts of dystrophin deficient muscles through matrix metalloproteinases Human molecular genetics, 2019; 34(5): 341-353.
Malik Ravinder, Meng Helen, Wongkongkathep Piriya, Corrales Christian I, Sepanj Niki, Atlasi Ryan S, Klärner Frank-Gerrit, Schrader Thomas, Spencer Melissa J, Loo Joseph A, Wiedau Martina, Bitan Gal   The molecular tweezer CLR01 inhibits aberrant superoxide dismutase 1 (SOD1) self-assembly The Journal of biological chemistry, 2019; 294(10): 3501-3513.
Ji Ying, Liu Xiangsheng, Huang Max, Jiang Jinhong, Liao Yu-Pei, Liu Qi, Chang Chong Hyun, Liao Han, Lu Jianqin, Wang Xiang, Spencer Melissa J, Meng Huan   Development of self-assembled multi-arm polyrotaxanes nanocarriers for systemic plasmid delivery in vivo Biomaterials, 2019; 192(10): 416-428.
Wang Derek W, Mokhonova Ekaterina I, Kendall Genevieve C, Becerra Diana, Naeini Yalda B, Cantor Rita M, Spencer Melissa J, Nelson Stanley F, Miceli M Carrie   Repurposing Dantrolene for Long-Term Combination Therapy to Potentiate Antisense-Mediated DMD Exon Skipping in the mdx Mouse Molecular therapy. Nucleic acids, 2018; 11(10): 180-191.
Kramerova Irina, Torres Jorge A, Eskin Ascia, Nelson Stanley F, Spencer Melissa J   Calpain 3 and CaMKIIβ signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy Human molecular genetics, 2018; 27(9): 1642-1653.
Gordish-Dressman Heather, Willmann Raffaella, Dalle Pazze Laura, Kreibich Arati, van Putten Maaike, Heydemann Ahlke, Bogdanik Laurent, Lutz Cathleen, Davies Kay, Demonbreun Alexis R, Duan Dongsheng, Elsey David, Fukada So-Ichiro, Girgenrath Mahasweta, Patrick Gonzalez J, Grounds Miranda D, Nichols Andy, Partridge Terry, Passini Marco, Sanarica Francesca, Schnell Frederick J, Wells Dominic J, Yokota Toshifumi, Young Courtney S, Zhong Zhong, Spurney Christopher, Spencer Melissa, De Luca Annamaria, Nagaraju Kanneboyina, Aartsma-Rus Annemieke   "Of Mice and Measures": A Project to Improve How We Advance Duchenne Muscular Dystrophy Therapies to the Clinic Journal of neuromuscular diseases, 2018; 5(4): 407-417.
Hicks Michael R, Hiserodt Julia, Paras Katrina, Fujiwara Wakana, Eskin Ascia, Jan Majib, Xi Haibin, Young Courtney S, Evseenko Denis, Nelson Stanley F, Spencer Melissa J, Handel Ben Van, Pyle April D   ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs Nature cell biology, 2018; 20(1): 46-57.
Quattrocelli Mattia, Capote Joanna, Ohiri Joyce C, Warner James L, Vo Andy H, Earley Judy U, Hadhazy Michele, Demonbreun Alexis R, Spencer Melissa J, McNally Elizabeth M   Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury PLoS genetics, 2017; 13(10): e1007070.
Yao Jiayi, Guihard Pierre J, Wu Xiuju, Blazquez-Medela Ana M, Spencer Melissa J, Jumabay Medet, Tontonoz Peter, Fogelman Alan M, Boström Kristina I, Yao Yucheng   Vascular endothelium plays a key role in directing pulmonary epithelial cell differentiation The Journal of cell biology, 2017; 216(10): 3369-3385.
Quattrocelli Mattia, Spencer Melissa J, McNally Elizabeth M   Outside in: The matrix as a modifier of muscular dystrophy Biochimica et biophysica acta. Molecular cell research, 2017; 1864(3): 572-579.
Young Courtney S, Mokhonova Ekaterina, Quinonez Marbella, Pyle April D, Spencer Melissa J   Creation of a Novel Humanized Dystrophic Mouse Model of Duchenne Muscular Dystrophy and Application of a CRISPR/Cas9 Gene Editing Therapy Journal of neuromuscular diseases, 2017; 4(2): 139-145.
Gibbs Elizabeth M, Marshall Jamie L, Ma Eva, Nguyen Thien M, Hong Grace, Lam Jessica S, Spencer Melissa J, Crosbie-Watson Rachelle H   High levels of sarcospan are well tolerated and act as a sarcolemmal stabilizer to address skeletal muscle and pulmonary dysfunction in DMD Human molecular genetics, 2016; 25(24): 5395-5406.
Kramerova Irina, Ermolova Natalia, Eskin Ascia, Hevener Andrea, Quehenberger Oswald, Armando Aaron M, Haller Ronald, Romain Nadine, Nelson Stanley F, Spencer Melissa J   Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A (calpainopathy) Human molecular genetics, 2016; 25(11): 2194-2207.