Recent progress in elucidating the mechanisms underlying muscular dystrophy and muscle disease has dramatically increased the number of protein targets available for potential drug treatment. Concurrently, new 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. While HTS has only been applied to a limited set of muscular dystrophy targets, early application of this approach has already lead to the development of therapeutics currently being tested in the clinic. This has lead to increased enthusiasm worldwide and among UCLA MDTRaC Investigators for designing and implementing muscular dystrophy relevant assays for drug discovery. UCLA has already made a tremendous commitment to HTS screening on campus in the form of the UCLA MSSR as one mechanism by which to facilitate translational medicine, in general. However, access to this resource is currently limited by available manpower, cell models, expertise and space for cell expansion and handling of muscle lineage and muscular dystrophy relevant cells. To address this limitation we propose to create a muscle relevant HTS Core that will utilize the robotics and imaging capabilities of the MSSR and will provide manpower, expertise, space, resources, and guidance on muscle cell and fibroblast culture. In this context the HTS Assay Core will:
Aim 1) advise users in assay development and provide access to available muscle and muscular dystrophy relevant cell models;
Aim 2) provide cell culture expansion and plating (in HTS format) and MSSR interfacing services, Aim 3) retrieve and analyze and mine data collected at the MSSR;
and Aim 4) aid in development and implementation of secondary assays for lead hit compound validation. Thus, the proposed core maximizes impact by leveraging the existing tremendous investment in HTS technology already available on campus and implementing the needed resources and skills to

Public Health Relevance

Development and implementation of muscle/muscular dystrophy relevant high throughput screens holds tremendous potential for identifying new therapeutics for treating muscle disease. Already this strategy has lead to the development of promising therapeutic candidates now in clinical trial for DMD.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Center Core Grants (P30)
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University of California Los Angeles
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DiFranco, Marino; Kramerova, Irina; Vergara, Julio L et al. (2016) Attenuated Ca(2+) release in a mouse model of limb girdle muscular dystrophy 2A. Skelet Muscle 6:11
Reyhan, Meral L; Wang, Zhe; Kim, Hyun J et al. (2016) Effect of free-breathing on left ventricular rotational mechanics in healthy subjects and patients with duchenne muscular dystrophy. Magn Reson Med :
Capote, Joana; Kramerova, Irina; Martinez, Leonel et al. (2016) Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotype. J Cell Biol 213:275-88
Srinivasan, Subashini; Kroeker, Randall M; Gabriel, Simon et al. (2016) Free-breathing variable flip angle balanced SSFP cardiac cine imaging with reduced SAR at 3T. Magn Reson Med 76:1210-6
Brown, Robert; Lee, Hane; Eskin, Ascia et al. (2016) Leveraging ancestry to improve causal variant identification in exome sequencing for monogenic disorders. Eur J Hum Genet 24:113-9
Young, Courtney S; Hicks, Michael R; Ermolova, Natalia V et al. (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 18:533-40
Kramerova, Irina; Ermolova, Natalia; Eskin, Ascia et al. (2016) Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A (calpainopathy). Hum Mol Genet 25:2194-2207
Gibbs, Elizabeth M; Marshall, Jamie L; Ma, Eva et al. (2016) High levels of sarcospan are well tolerated and act as a sarcolemmal stabilizer to address skeletal muscle and pulmonary dysfunction in DMD. Hum Mol Genet :
Mokhonova, Ekaterina I; Avliyakulov, Nuraly K; Kramerova, Irina et al. (2015) The E3 ubiquitin ligase TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2. Hum Mol Genet 24:2873-83
Arboleda, Valerie A; Lee, Hane; Dorrani, Naghmeh et al. (2015) De novo nonsense mutations in KAT6A, a lysine acetyl-transferase gene, cause a syndrome including microcephaly and global developmental delay. Am J Hum Genet 96:498-506

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