
Melissa Spencer, Ph.D.
Bio
Melissa Spencer, Ph.D., studies the biological causes of genetically inherited muscular dystrophies in order to identify novel treatments and improve quality of life for patients. Spencer takes a multidisciplinary approach to her work to gain insights into how muscular dystrophies relate to the body’s natural processes and ensure that findings will be translatable from animal models to humans.
One area of focus in Spencer’s lab is Duchenne muscular dystrophy, which affects approximately 1 in 5,000 boys in the U.S. and is the most common fatal childhood genetic disease. Duchenne occurs through mutations in a gene that produces dystrophin, a protein that helps strengthen and connect muscle fibers. Duchenne mutations cause abnormally low production of the dystrophin protein, which in turn causes muscles to degenerate and become progressively weaker.
Spencer is particularly interested in how the immune system’s natural muscle repair processes go awry in patients with Duchenne, exacerbating disease symptoms. In patients without Duchenne, the immune system plays a key role in repairing injured muscle throughout life. Duchenne causes muscle weakness and degeneration, sending the immune response process into overdrive. Constant wound repair leads to inflammation, which causes muscle tissue to scar and thicken, ultimately limiting muscle function. Spencer has focused on studying the components of the immune system involved in this process in order to identify cellular or protein targets for therapies that rein in abnormal immune response. This work has led to the identification of a drug that is currently being evaluated in preclinical studies.
Spencer is simultaneously investigating another potential therapeutic avenue to treat Duchenne. In collaboration with stem cell center colleagues, Spencer developed an approach that uses the stem cell gene editing platform CRISPR/Cas9 to correct the genetic mutations that cause Duchenne. She and her collaborators are now working on identifying novel delivery methods such as nanotechnologies that could bring this promising therapy to patients with minimal side effects.
Spencer is also collaborating on the development of a drug to treat limb girdle muscular dystrophy type 2A, also known as primary calpainopathy, a genetic disease characterized by progressive weakness in the limb and shoulder girdle muscles, mainly those around the hips and shoulders. This drug is currently being evaluated in animal models.
Spencer earned her doctorate in physiological science from UCLA.
Publications
- A Small-Molecule Approach to Restore a Slow-Oxidative Phenotype and Defective CaMKIIβ Signaling in Limb Girdle Muscular DystrophyPublished in Cell on Wednesday, October 21, 2020
- Calpain 3 and CaMKIIβ signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophyPublished in Human Molecular Genetics on Thursday, March 8, 2018
- ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCsPublished in Nature Cell Biology on Monday, December 18, 2017
- Creation of a Novel Humanized Dystrophic Mouse Model of Duchenne Muscular Dystrophy and Application of a CRISPR/Cas9 Gene Editing TherapyPublished in Journal of Neuromuscular Diseases on Tuesday, May 30, 2017
- Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotypePublished in Journal of Cell Biology on Monday, April 18, 2016
- Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A Published in Human Molecular Genetics on Tuesday, March 22, 2016
- Attenuated Ca2+ Release in a Mouse Model of Limb Girdle Muscular Dystrophy 2APublished in Skeletal Muscle on Wednesday, February 24, 2016
- A Single CRISPR-Cas9 Deletion Strategy that Targets the Majority of DMD Patients Restores Dystrophin Function in hiPSC-Derived Muscle CellsPublished in Cell Stem Cell on Thursday, February 11, 2016
- A reporter mouse for optical imaging of inflammation in mdx musclesPublished in Skeletal Muscle on Thursday, April 30, 2015
- Dantrolene Enhances Antisense-Mediated Exon Skipping in Human and Mouse Models of Duchenne Muscular DystrophyPublished in Science Translational Medicine on Wednesday, December 12, 2012
- Impaired calcium calmodulin kinase signaling and muscle adaptation response in the absence of calpain 3 Published in Human Molecular Genetics on Saturday, April 14, 2012
- Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-betaPublished in Journal of Clinical Investigation on Monday, May 18, 2009
Honors & Affiliations
Honors
- Golden Test Tube Award, UCLA Department of Neurology, 2018
- Presidential Early Career Award For Scientists and Engineers, National Science Foundation, 2001
Affiliations
- American Society for Cell Biology
- World Muscle Society
- Scientific Advisory Committee, Muscular Dystrophy Association
- Scientific Advisory Board, Parent Project Muscular Dystrophy
- Chairman of Scientific Advisory Board, Coalition to Cure Calpain 3
Funding
Spencer's research is funded by the National Institutes of Health's National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Coalition to Cure Calpain 3, the Muscular Dystrophy Association of America, the Jessie Smith Noyes Foundation, Strongbridge Biopharma and the University of Florida.