Carrie Miceli, Ph.D.
Professor of Microbiology Immunology and Molecular Genetics
Co-Director Center for Duchenne Muscular Dystrophy at UCLA
Director, CDMD Cell and Tissue Repository.
California Center for Rare Diseases
Molecular Biology Institute
Graduate Programs in Bio-Science Homes: Immunity Microbes and Molecular Pathogenesis, Cell and Developmental Biology.
The Miceli lab is focused around two main research topics: T cell biology and Duchenne Muscular Dystrophy (DMD). DMD is a lethal genetic disease of childhood, caused by mutations in DMD, which encodes the dystrophin protein. Without functional dystrophin, defects in sarcolemma stabilization lead to progressive muscle damage, while inherent stem cell defects limit efficiency of regeneration. Immune cells infiltrate muscle in response to damage, coordinating muscle satellite cell activation and muscle regeneration. In the face of the chronic damage in DMD, inflammation also drives fibrosis, promoting scarring and further limiting muscle regeneration. Progressive muscle weakness leads to loss of virtually all muscle function, respiratory and cardiac failure, and death between ages 20-30. The Miceli lab works closely with the CDMD clinic, clinical trials population and industry partners to use DMD clinic and clinical trial tissue sample to model human DMD, screen for new drugs/targets, assess therapeutic efficacy and mechanisms of action and immune consequences of dystrophin replacement and immune modulating therapies.
Because DMD patient biopsy tissue is of limited availability, we are developing and applying technology for robust assessment of single cell multi-parameter immune and muscle lineage cell surface marker and gene expression, including TCR/BCR cell V region usage from cryopreserved PBMC, and frozen muscle biopsy tissue. Additionally, we developed patient mutation specific DMD skeletal muscle and cardiac culture models. We have active collaborations with industry partners involved in dystrophin replacement/rescue and immune suppression in DMD, and access to remnant trial tissue and clinic samples for our studies. By examining the consequences of therapeutics on immunity, muscle regeneration, fibrosis and tissue tolerance in human DMD, we hope to identify therapeutic mechanism of action and efficacy, cell and molecular targets for drug discovery, and potential barriers to successful treatment. We hypothesize that these studies will identify novel immune and myogenic drivers of muscle regeneration, fibrosis and immune tolerance in human DMD.
Dr. Miceli is a professor in the Department of Microbiology Immunology and Molecular genetics. She received her BA from UCSD in Biochemistry and Cell Biology, her PhD from Duke University studying the role of T cells in human kidney allograft rejection (Olja Finn, mentor) and did postdoctoral work at Stanford elucidating molecular mechanisms of CD4, CD8, Lck and TCR coreceptor functions (Jane Parne’s laboratory). In her own laboratory her group has identified mechanisms and modulators of TCR signal specificity and T cell function, with broad application to signal transduction in general. In 2007, with colleagues, Dr. Miceli founded the Center for Duchenne Muscular Dystrophy (CDMD), which formed and catalyzed new DMD team science approaches to translational research, drug discovery, and clinical trial development on campus and nationwide. Combining her expertise in these areas she is now focused on dystrophin replacement therapies and immune drivers of regeneration, fibrosis and muscle tissue tolerance.
Barthélémy, F, Wang, RT, Hsu, C, Douine, ED. Nelson, SF and Miceli, MC.. Targeting RyR activity boosts antisense exon 44 and 45 skipping in human DMD skeletal or cardiac muscle culture models. Submitted
Gibbs, EM, Barthélémy, F. Douine ED , Hardiman, N, Shieh, PB, Khanlou, N, Crosbie-Watson, RHC*, Nelson, SF* and Miceli, MC*. Large in-frame 5’deletions in DMD associated with mild Duchenne Muscular Dystrophy: two case reports and a review of the literature. Submitted. *denotes equal contribution, Miceli, Nelson, and Crosbie-Watson share senior authorship. Miceli Corresponding Author. Submitted
Wang, DW, Mokhonova, E, Kendall, GC, Becerra, D., Naeini, Y, Spencer, MJ, Cantor, R. Nelson, SF*, Miceli, MC* Repurposing Dantrolene for Long-term Combination Therapy to Potentiate Antisense-Mediated DMD Exon Skipping in the mdx mouse. Molecular Therapy: Nucleic Acids. (2018) Nucleic Acids Vol. June 11: 180-191 *denotes equal contributions. Miceli corresponding author.
McMoran Brian J, Miceli, MC and Baum L. Lectin-binding characterizes the healthy human skeletal muscle glycophenotype and identifies disease-specific changes in dystrophic muscle. Glycobiology, Volume 27, Issue 12, 1 December 2017, Pages 1134–1143,
Nelson, Stanley F.*, Miceli MC*# FDA Approval of Eteplirsen for Duchenne Muscular Dystrophy. *denotes equal contributions #corresponding author JAMA 317, (14):1481-1482. doi:10.1001/jama.2017.2601
Victor, RG, Sweeney, HL, Finkel , R., McDonald, C., Byrne, B. Eagle, Goemans, N, Vandenborne, K, Alberto L, Dubrovsky, L, Topaloglu, H. Miceli, M. C., Furlong, P, Landry, J, Elashoff, R., Cox, D., For the Tadalafil DMD Study Group. A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy. 2017 Oct 24; 89(17): 1811–1820. PMCID: PMC5664308 PMID:28972192
Young CS, Hicks MR, Ermolova NV, Nakano H, Jan M, Younesi S, Karumbayaram S, Kumagai-Cresse C, Wang D, Zack JA, Kohn DB, Nakano A, Nelson SF, Miceli MC, Spencer MJ, Pyle AD. (2016). 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 Apr 7;18(4):533-40 PMCID: PMC4826286.
Miceli, MC*, Nelson, SF* The case for eteplirsen: Paving the way for precision medicine. *denotes equal contributions. Molecular Genetics and Metabolism. 118, 2, 70–71, 2016
Capote J, Kramerova I, Martinez L, Vetrone S, Barton ER, Sweeney HL, Miceli MC, Spencer, MJ. (2016). Osteopontin Ablation Ameliorates Muscular Dystrophy by shifting macrophages to a pro-regenerative phenotype. J Cell Biol. 25;213(2):275-88. 2016
Crocetti, J*, Silva, O*, Humphries, L., Tibbs, MS, Miceli, M. C. Selective phosphorylation of the Dlg1AB variant is critical for TCR-induced p38 activation and induction of pro-inflammatory cytokines in CD8+ T cells, Journal of Immunology, 193, 2651-2660. 2014 * denotes equal contributions
Wang, RT, Barthelemy, F. Martin, ED, Douine, D, Eskin, A, Lucas, K, Lavigne, JA. L Peay, H, Khanlou, N, Cantor, RM. Cantor, Miceli. MC* and Nelson SF*. DMD Genotype Correlations from the Duchenne Registry: endogenous exon skipping, is a factor in prolonged ambulation for individuals with a defined mutation sub-type. Human Mutation. 39:1193–1202. 2018. * denotes equal contributions
Silva, O, Crocetti, J, Humphries, J, Burkhardt, J and M. C. Miceli (2015). Discs Large Homolog 1 splice variants regulate p38 dependent and Independent Effector Functions in CD8+ T cells. PLOS One. Online July 17, (2015).
Nelson, MD, Rader, F. Tang, X, Tavyev, J., Nelson, SF, Miceli, M. Carrie, Elashoff, R.M., Sweeney, H. L. and Victor, RG. PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy. Neurology, 82, 2085-2091, 2014
Kendall, GC, Mokhonova, E. Moran, M, Sejbuk, N, Wang, DW, Silva, O, Wang, RT, Martinez, Lu, QL, Damoiseaux, R, Spencer, MJ *, Nelson, SF* Miceli, MC*†. Dantrolene Enhances Antisense-Mediated Exon Skipping in Human and Mouse Models of Duchenne Muscular Dystrophy. Science Translational Medicine 4, 164, p. 164ra160, December 2012 * denotes equal contributions
Vetrone, S.A., Montecino-Rodriguez, E., Kudryashova, E., Kramerova, I., Hoffman, E.P., Liu, S.D., Miceli, M.C., Spencer M.J. Osteopontin promotes fibrosis in Mdx muscle through modulation of immune cell subsets and intramuscular TGFbeta. Journal of Clinical Investigation, 119 (6):1583-1594, 2009. PMCID: PMC2689112
Liu, S.D., Tomassian, T., Miceli, M.C. Galectin-1 tunes TCR binding and signal transduction to regulate CD8 burst size. Journal of Immunology, 182 (9):5283-5295, 2009.
Liu, SD, Chung, CD, Tomassian, T, Pang, M, Baum, LG, Miceli, MC. Endogenous galectin-1 functions to enforce class I restricted TCR functional fate decisions in thymocytes. Blood, 112 (1):120-130, 2008.
Round, JL, Humphries, LA, Tomassian, T, Mittelstadt, P, Zhang M, Miceli, MC. Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kB transcription factors. Nature Immunology, 8 (2):154-161, 2007.
Round, J.L., Tomassian, T., Zhang, M., Patel, P., Schoenberger, S.P., Miceli, M.C. Dlgh1 coordinates actin polymerization, synaptic TCR and lipid raft aggregation and effector function in T lymphocytes. Journal of Experimental Medicine, 201 (3):419-430, 2005. PMCID: PMC2213022
Moran, M. and Miceli, M.C. Engagement of GPI-anchored T cell CD48 contributes to TCR signals and cytoskeletal reorganization: a role for lipid rafts in T cell activation. Immunity, 9: 787-796, 1998.