The Muscle Phenotyping and Imagine Core is designed to enable muscle and non-muscle researchers alike to access a variety of assessment tools for the study of muscle phenotypes. The Core will be useful in 3 main ways. First, the Core will provide a means for investigators to test lead therapeutic compounds in mice to evaluate their effect on muscle pathology. Drugs that delay the onset of disease or reduce muscle pathology will be identified through the small molecule high-throughput screen (Core B) or can be investigator initiated. For these assessments, both traditional (histology, muscle function tests) and non-traditional (optical imaging, MRI) methods will be available for researchers to utilize on a fee for service basis. Second, because most muscular dystrophies involve changes in the dystrophin-glycoprotein complex, biochemical assessments of muscular dystrophy-related proteins will be an additional service offered by this core. Finally, as more and more researchers are making use of transgenic mouse technology, it has become necessary for these individuals to explore muscle phenotypes in their novel knock out and transgenic animals. Since these researchers lack the necessary experience to assess muscle tissue, this Core will provide access to resources, expertise and training necessary to allow them to explore muscle morphology and function in a manner that would not otherwise be available to them.
The Aims of the Core are:
Aim 1 : To enable researchers the opportunity, resources and training to evaluate muscle phenotypes in transgenic mice;
Aim 2 : To enable researchers the opportunity, resources and training to evaluate the efficacy of pharmacological compounds on muscular dystrophy pathogenesis, using quantitative functional and histological outcome measures as well as state-of-the art imaging technologies;
Aim 3 : To enable researchers the opportunity, resources and training to evaluate biochemical outcomes following treatments with pharmacological compounds.
This core facility will be a valuable resource to Center Investigators as well as to the greater dystrophy community by facilitating rapid, pre-clinical testing of compounds. The most promising drugs identified through these combined efforts will be taken to human clinical trials.
|Villalta, S Armando; Rosenthal, Wendy; Martinez, Leonel et al. (2014) Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy. Sci Transl Med 6:258ra142|
|Ermolova, N V; Martinez, L; Vetrone, S A et al. (2014) Long-term administration of the TNF blocking drug Remicade (cV1q) to mdx mice reduces skeletal and cardiac muscle fibrosis, but negatively impacts cardiac function. Neuromuscul Disord 24:583-95|
|Swaggart, Kayleigh A; Demonbreun, Alexis R; Vo, Andy H et al. (2014) Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair. Proc Natl Acad Sci U S A 111:6004-9|
|Nelson, Michael D; Rader, Florian; Tang, Xiu et al. (2014) PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy. Neurology 82:2085-91|
|Lee, Hane; Deignan, Joshua L; Dorrani, Naghmeh et al. (2014) Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 312:1880-7|
|Sareen, Dhruv; O'Rourke, Jacqueline G; Meera, Pratap et al. (2013) Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Sci Transl Med 5:208ra149|
|Rudnik-Schoneborn, Sabine; Senderek, Jan; Jen, Joanna C et al. (2013) Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations. Neurology 80:438-46|
|Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J et al. (2013) The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy. FEBS J 280:4210-29|
|Wan, Jijun; Yourshaw, Michael; Mamsa, Hafsa et al. (2012) Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. Nat Genet 44:704-8|
|Kudryashova, Elena; Kramerova, Irina; Spencer, Melissa J (2012) Satellite cell senescence underlies myopathy in a mouse model of limb-girdle muscular dystrophy 2H. J Clin Invest 122:1764-76|
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