Latest News

Affiliations

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.

Research Interests

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.

Biography

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.

Representative Publications

Scripture-Adams DD^‡, Chesmore, K.N. ^‡, Barthélémy, F Wang RT, Nieves-Rodriguez S, Wang DW, Mokhonova EI, Douine ED, Wan J, Little I, Rabichow LN, * Nelson SF, and * Miceli MC. Single nuclei transcriptomics of muscle reveals intra-muscular cell dynamics linked to dystrophin loss and rescue, Communications Biology 5, 989, 2022.  (*joint senior authors,^‡joint first authors).

Barthélémy F*, Santoso JW*, Rabichow L, Jin R, Little I, Nelson SF, McCain ML*, Miceli MC*. Modeling Patient-Specific Muscular Dystrophy Phenotypes and Therapeutic Responses in Reprogrammed Myotubes Engineered on Micromolded Gelatin Hydrogels. Front Cell Dev Biol 10:830415. 2022. PMID: 35465312; PMCID: PMC9020228. *equal contributions.

Barthélémy, F*, Woods J *, Nieves -Rodriguez, S, Wang, R, Wanagat J., *Miceli, MC, *Nelson, SF.  A Well Tolerated Core Needle Biopsy Process for Children and Adults.  Muscle and Nerve 62(6):688-698. 2020. PMID: 32820569; PMCID: PMC7756388. (Journal cover)

Barthélémy, F, Wang, RT, Hsu, C, Douine, ED. Nelson, SF and Miceli, M.C.  Targeting RyR activity boosts antisense exon 44 and 45 skipping in human DMD skeletal or cardiac muscle culture models. Molecular Therapy, Nucleic Acids, 18:580-589. 2019. PMID: 316787344; PMCID: PMC6838898.

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. Neuromuscular Disorders, 2019. *

Wang, DW, Mokhonova, EI, 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.

Wang, RT*, Barthelemy, F*. Martin, ED, Douine, D, Eskin, A. Lucas, Lavigne, JA. L Peay, H., Khanlou, N, Cantor, RM. Cantor, Miceli. M.C.*, 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. PMID: 29907980; PMCID: PMC6175390 *denotes equal contributions. (Journal Cover, highlighted as Editor’s Choice.

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 PMID: 26877224; PMCID: PMC4826286  (Journal cover)

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

Kendall GC*, Mokhonova E*, Moran M, Sejbuk NE, Wang DW, Silva O, Wang RT, Martinez Lu, 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. 164, 2012. PMID: 23241744 * equal contributions. (Journal Cover, Perspective in Science).

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

Tomassian, T., Humphries, L., Lui, S.D., Silva, O. Brooks, D., Miceli, M.C.  Caveolin-1 orchestrates synaptic polarity, signal specificity and function in CD8 T cells.  Journal of Immunology, 187:2993-3002, 2011.

Liu, S.D., Chung, C.D., Tomassian, T., Pang, M., Baum, L.G., Miceli, M.C.  Endogenous galectin-1 functions to enforce class I restricted TCR functional fate decisions in thymocytes.  Blood, 112 (1):120-130, 2008. (editorials in Blood, Nature Reviews Immunology, and on the Nature Glycomics Gateway). PMCID: PMC2435683

Round, J.L., Humphries, L.A., Tomassian, T., Mittelstadt, P., Zhang M., Miceli, M.C.  Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors.  Nature Immunology, 8 (2):154 – 161, 2007. ((high-lighted with editorials in Nature Immunology, Trends in Immunology and on the Nature Signaling Gateway).

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

Liu, S.D., Chung, C.D., Tomassian, T., Pang, M., Baum, L.G., Miceli, M.C.  Endogenous galectin-1 functions to enforce class I restricted TCR functional fate decisions in thymocytes.  Blood, 112 (1):120-130, 2008. (editorials in Blood, Nature Reviews Immunology, and on the Nature Glycomics Gateway). PMCID: PMC2435683

Moran, M., 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.