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.
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