M. Carrie Miceli, Ph.D.

Department Address:
276B Biomedical Sciences Research Building
CAMPUS - 157005

Laboratory Address:
257 Basic Sciences Research Building
Los Angeles, CA 90095

Work Address:
Department of Microbiology, Immunology, and Molecular Genetics
Los Angeles, CA 90095

Co-Director, Center for Duchenne Muscular Dystrophy
Professor, Microbiology, Immunology & Molecular Genetics
Member, Cell & Developmental Biology GPB Home Area, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, JCCC Signal Transduction and Therapeutics Program Area

Dr. M. Carrie Miceli graduated with a BA in Biochemistry and Cell Biology from UCSD. She earned her Ph.D. in Immunology from Duke University for studies elucidating T cell mechanisms of human kidney allograft rejection. Her postdoctoral work at Stanford focused on the molecular basis of T cell antigen recognition and signaling, characterizing roles for CD8, CD4 and Lck in T cell receptor signaling. Since her faculty appointment at UCLA in 1993, her lab has investigated the cellular and molecular basis of T cell immunity. In addition to dissecting molecular mechanisms of T cell activation, tolerance and fate, her research has had broad relevance to cell biology and signal transduction. Recently, she has developed an interest in the role of inflammation in Duchenne Muscular Dystrophy with Dr. Spencer. In 2005, together with Dr. Nelson, Dr. Miceli developed a program designing and implementing cellular assays for high throughput small molecule screening for DMD-drug discovery. She served as a PI/Co-PI on DOD, NIH and CIRM grants aimed at identifying enhancers of DMD exon skipping; resulting in the discovery of compounds that synergizes with anti-sense oligonucleotide mediated DMD exon skipping, award of a provisional patent, licensing negotiations and collaborations with several biotech companies. She directs the High Throughput Screening and Muscular Dystrophy Cell Models Repository Core, which expands banks, distributes and reprograms DMD patient fibroblasts for use in drug development, and serves on the Administrative Core for the NIH funded P30 Muscular Dystrophy Core Center. Dr. Miceli is a Scientific Advisor for PPMD, CureDuchenne, Imaging DMD and the Lily DMD Tadalifil Phase II Clinical Trial and is on the Data and Safety Monitoring Board for the BMD/sIBM Follistatin Gene Transfer Clinical Trial. She reviews grants for PPMD, Dutch-PPMD, NIH and DOD. She has chaired the congressionally mandated DOD DMD study section and both annual PPMD and Duchenne Parent Project Italy Scientific Sessions. She serves as a Vice Chair of Microbiology, Immunology and Molecular Genetics.

In 2007, Drs. M. Carrie Miceli, Melissa Spencer, and Nelson launched the Center for Duchenne Muscular Dystrophy at UCLA to improve education, accelerate research and promote translation into clinic for the most common lethal genetic disease of childhood. This multidisciplinary effort has transformed research approaches on campus, providing essential seed grants and an intellectual environment to facilitate progress. The CDMD has organized the first multidiscliplinary care clinic for Duchenne in Southern California, documented to extend lifespan by 10 years and dramatically improve quality of life. The Center is now participating in multiple clinical trials for Duchenne, both serving as a site for CDMD investigator initiated trials as well as participating in multi-center clinical trials sponsored by industry and other academic institutions. Since the first funding of the CDMD Core Center in 2009, the Center has successfully expanded the number of multidisciplinary collaborations focused on muscular dystrophy research and accelerated the discovery and testing of potential therapeutics, with 13 laboratories now focused on Duchenne. At the center of the research accomplishments is the collaborative efforts of Drs. Miceli, Nelson and Spencer’s laboratories to identify enhancers of exon skipping to restore reading frame and a partially functional dystrophin protein. This work was published in Science Translational Medicine in December 2012, featured on the cover with commentary in Science, and was selected by the Director of NIAMS as a research highlight. With funding from the California Institute of Regenerative Medicine, they are now moving combination therapy for exon skipping toward clinical development repair mutant mRNA in situ. This collaborative research endeavor exemplifies the CDMD mission of using basic discovery to identify therapeutic targets, screen for drugs and develop them for human clinical trial in DMD. There are a number of therapeutic strategies poised to translate from the bench into clinic for Duchenne, and the CDMD is committed to facilitating their development. This creates exciting research opportunities on campus, in partnership with biotechnology firms, and in collaboration with extramural researchers. The CDMD facilitates activities on campus through an interdepartmental and inter-institutional approach to bring researchers together through a pilot and feasibility program, bi-weekly seminar series, establishment of a new PhD training program, establishment of cores to facilitate study of muscular dystrophy.

Drs Miceli and Nelson were motivated to re-focus their laboratories around DMD discovery and drug development upon the diagnosis of their youngest son with Duchenne Muscular Dystrophy in 2004.


A selected list of publications:

Humphries Lisa A, Shaffer Meredith H, Sacirbegovic Faruk, Tomassian Tamar, McMahon Kerrie-Ann, Humbert Patrick O, Silva Oscar, Round June L, Takamiya Kogo, Huganir Richard L, Burkhardt Janis K, Russell Sarah M, Miceli M Carrie   Characterization of in vivo Dlg1 deletion on T cell development and function PloS one, 2012; 7(9): e45276.
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.
Tomassian Tamar, Humphries Lisa A, Liu Scot D, Silva Oscar, Brooks David G, Miceli M Carrie   Caveolin-1 orchestrates TCR synaptic polarity, signal specificity, and function in CD8 T cells Journal of immunology (Baltimore, Md. : 1950), 2011; 187(6): 2993-3002.
Nelson, Stanley F., Crosbie, Rachelle H., Miceli, M. Carrie, and Spencer, Melissa J. Emerging Genetic Therapies to Treat Duchenne Muscular Dystrophy. , 22 (5): , 2009   Emerging Genetic Therapies to Treat Duchenne Muscular Dystrophy, Current Opinion in Neurology, 2009; 22: 532-538.
Liu Scot D, Tomassian Tamar, Bruhn Kevin W, Miller Jeff F, Poirier Françoise, Miceli M Carrie   Galectin-1 tunes TCR binding and signal transduction to regulate CD8 burst size Journal of immunology (Baltimore, Md. : 1950), 2009; 182(9): 5283-95.
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.
Liu Scot D, Whiting Chan C, Tomassian Tamar, Pang Mabel, Bissel Stephanie J, Baum Linda G, Mossine Valeri V, Poirier Françoise, Huflejt Margaret E, Miceli M Carrie   Endogenous galectin-1 enforces class I-restricted TCR functional fate decisions in thymocytes Blood, 2008; 112(1): 120-30.
Motran Claudia C, Molinder Karen M, Liu Scot D, Poirier Françoise, Miceli M Carrie   Galectin-1 functions as a Th2 cytokine that selectively induces Th1 apoptosis and promotes Th2 function European journal of immunology, 2008; 38(11): 3015-27.
Round June L, Humphries Lisa A, Tomassian Tamar, Mittelstadt Paul, Zhang Min, Miceli M Carrie   Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors Nature immunology, 2007; 8(2): 154-61.
Zhang Min, Moran Miriana, Round June, Low Teresa A, Patel Viresh P, Tomassian Tamar, Hernandez Joseph D, Miceli M Carrie   CD45 signals outside of lipid rafts to promote ERK activation, synaptic raft clustering, and IL-2 production Journal of immunology (Baltimore, Md. : 1950), 2005; 174(3): 1479-90.
Round June L, Tomassian Tamar, Zhang Min, Patel Viresh, Schoenberger Stephen P, Miceli M Carrie   Dlgh1 coordinates actin polymerization, synaptic T cell receptor and lipid raft aggregation, and effector function in T cells The Journal of experimental medicine, 2005; 201(3): 419-30.
Kersh Ellen N, Kaech Susan M, Onami Thandi M, Moran Miriana, Wherry E John, Miceli M Carrie, Ahmed Rafi   TCR signal transduction in antigen-specific memory CD8 T cells Journal of immunology (Baltimore, Md. : 1950), 2003; 170(11): 5455-63.
Huang Tiffany T, Zong Yumei, Dalwadi Harnisha, Chung Chan, Miceli M Carrie, Spicher Karsten, Birnbaumer Lutz, Braun Jonathan, Aranda Richard   TCR-mediated hyper-responsiveness of autoimmune Galphai2(-/-) mice is an intrinsic naïve CD4(+) T cell disorder selective for the Galphai2 subunit International immunology, 2003; 15(11): 1359-67.
Kitchen Scott G, LaForge Stuart, Patel Viresh P, Kitchen Christina M, Miceli M Carrie, Zack Jerome A   Activation of CD8 T cells induces expression of CD4, which functions as a chemotactic receptor Blood, 2002; 99(1): 207-12.
Brewer C Fred, Miceli M Carrie, Baum Linda G   Clusters, bundles, arrays and lattices: novel mechanisms for lectin-saccharide-mediated cellular interactions Current opinion in structural biology, 2002; 12(5): 616-23.
Patel VP, Moran M, Low TA, Miceli MC   A molecular framework for two-step T cell signaling: Lck Src homology 3 mutations discriminate distinctly regulated lipid raft reorganization events Journal of immunology (Baltimore, Md. : 1950) , 2001; 166(2): 754-64.
Miceli MC, Moran M, Chung C, Patel VP, Low T and Zinnanti W   Costimulation and counter-stimulation: lipid raft clustering controls TCR signaling and functional outcomes, Seminars in Immunology, 2001; 13:2.: 115-128 .
Chung CD, Patel VP, Moran M, Lewis LA, Miceli MC   Galectin-1 induces partial TCR zeta-chain phosphorylation and antagonizes processive TCR signal transduction Journal of immunology (Baltimore, Md. : 1950) , 2000; 165(7): 3722-9.
Vespa GN, Lewis LA, Kozak KR, Moran M, Nguyen JT, Baum LG, Miceli MC   Galectin-1 specifically modulates TCR signals to enhance TCR apoptosis but inhibit IL-2 production and proliferation Journal of immunology (Baltimore, Md. : 1950) , 1999; 162(2): 799-806.
Moran M and Miceli MC   Engagement of GPI-linked CD48 Contributes to TCR Signals and Cytoskeletal Reorganization: A Role for Lipid Rafts in T Cell Activation, Immunity, 1998; 9: 787-796.
Chung CD, Lewis LA, Miceli MC   T cell antigen receptor-induced IL-2 production and apoptosis have different requirements for Lck activities Journal of immunology (Baltimore, Md. : 1950) , 1997; 159(4): 1758-66.
Lewis LA, Chung CD, Chen J, Parnes JR, Moran M, Patel VP, Miceli MC   The Lck SH2 phosphotyrosine binding site is critical for efficient TCR-induced processive tyrosine phosphorylation of the zeta-chain and IL-2 production Journal of immunology (Baltimore, Md. : 1950) , 1997; 159(5): 2292-300.