Recent progress in elucidating mechanisms underlying muscular dystrophy and muscle disease has dramatically increased the number of potentially druggable targets available for therapeutic intervention. Concurrently, hew approaches have increased the number of compounds that can be tested for activity against these targets. Together, these trends have stimulated the adoption of high-throughput screening (HTS) as a primary tool for early-stage drug discovery. HTS has already been applied to a limited set of muscular dystrophy targets, leading to therapeutics currently being tested in the clinic. This has increased enthusiasm worldwide and among CDMD Investigators for designing and implementing muscular dystrophy relevant HTS assays for drug discovery and elucidation of basic aspects of muscle cell biology. UCLA has already made a tremendous commitment to HTS screening on campus through the Molecular Shared Screening Resource (MSSR) to facilitate translational medicine, in general. Core B extends this set of resources to facilitate the screening of muscle/dystrophy relevant targets by providing manpower, cell models, expertise, eqiuipment and space for cell reprogramming, expansion and banking to support muscle centric projects. A major focus of the core is developing and distributing human patient cell based dystrophy models, including iDRM.(induced directly reprogrammable myotubes) and IPSC (induced pleurepotent stem cells), from patients with Duchenne and other dystrophies for use in HTS and validation of target hits and other interventions. Thus, the core maximizes impact by leveraging the existing UCLA investment in HTS technology by providing the needed resources and skills to fill the gaps to make muscle/dystrophy relevant assays readily and simply feasible on campus for center members.
Aim 1) To advise and assist users in muscle centric HTS assay development, application and data analysis in collaboration with the MSSR;
Aim 2) To develop, validate expand, bank and distibute primary/reprogrammed cells derived from Duchenne and other dystrophy patients;
Aim 3) To provide support, expertise, equipment and BSL2+ cuture space for utilization of developed cell based models for drug/therapy/target validation.
|Aliotta, Eric; Moulin, Kévin; Magrath, Patrick et al. (2018) Quantifying precision in cardiac diffusion tensor imaging with second-order motion-compensated convex optimized diffusion encoding. Magn Reson Med 80:1074-1087|
|Hicks, Michael R; Hiserodt, Julia; Paras, Katrina et al. (2018) ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs. Nat Cell Biol 20:46-57|
|Armstrong, Tess; Dregely, Isabel; Stemmer, Alto et al. (2018) Free-breathing liver fat quantification using a multiecho 3D stack-of-radial technique. Magn Reson Med 79:370-382|
|Wang, Richard T; Barthelemy, Florian; Martin, Ann S et al. (2018) DMD genotype correlations from the Duchenne Registry: Endogenous exon skipping is a factor in prolonged ambulation for individuals with a defined mutation subtype. Hum Mutat 39:1193-1202|
|Wang, Derek W; Mokhonova, Ekaterina I; Kendall, Genevieve C et al. (2018) Repurposing Dantrolene for Long-Term Combination Therapy to Potentiate Antisense-Mediated DMD Exon Skipping in the mdx Mouse. Mol Ther Nucleic Acids 11:180-191|
|Kramerova, Irina; Torres, Jorge A; Eskin, Ascia et al. (2018) Calpain 3 and CaMKII? signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy. Hum Mol Genet 27:1642-1653|
|Gibbs, Elizabeth M; Crosbie-Watson, Rachelle H (2017) A Simple and Low-cost Assay for Measuring Ambulation in Mouse Models of Muscular Dystrophy. J Vis Exp :|
|Peter, Angela K; Miller, Gaynor; Capote, Joana et al. (2017) Nanospan, an alternatively spliced isoform of sarcospan, localizes to the sarcoplasmic reticulum in skeletal muscle and is absent in limb girdle muscular dystrophy 2F. Skelet Muscle 7:11|
|Young, Courtney S; Mokhonova, Ekaterina; Quinonez, Marbella et al. (2017) Creation of a Novel Humanized Dystrophic Mouse Model of Duchenne Muscular Dystrophy and Application of a CRISPR/Cas9 Gene Editing Therapy. J Neuromuscul Dis 4:139-145|
|Rai, Muhammad Farooq; Duan, Xin; Quirk, James D et al. (2017) Post-Traumatic Osteoarthritis in Mice Following Mechanical Injury to the Synovial Joint. Sci Rep 7:45223|
Showing the most recent 10 out of 71 publications