Cell Core C continues FSHD biomaterials acquisition to support Projects 1, 2, and 3, as well as the FSHD research community with our cell repository distribution program. A new focus on FSHD families with nonmanifesting carriers of the genetic signature will expand on the usefulness of our repository by providing DNA from blood, muscle biopsy tissue and cells derived from biopsies for investigating modifiers of FSHD pathology. Subjects recruited into the program with confirmatory genetic testing will be asked to participate and give informed consent. Biceps muscles, which tend to be affected early in FSHD pathology, will be biopsied and coded to mask patient identity (Aim 1). Biopsy material will be distributed for histology (Aim 2), RNA screening (Proj. 2, Aim 1), which will inform xenograft studies (Proj. 3, Aims 1&2), and fiber-based xenografts (Proj. 3, Aim 1). Primary muscle cells will be isolated (Aim 2) and expanded for banking and distribution (Aim 3);CD56+ muscle cells will be provided to Center investigators for RNA screening (Proj. 2, Aim 1), study of the epigenetic regulation of DUX4-fl (Proj. 2, Aim 2), the development of antisense morpholino drugs (Proj. 2, Aim 3) and for cell-based xenografts (Proj. 3, Aim 2). Cell availability is advertised on the FSH Society and Center websites and at the annual FSHD Research International Consortium Meeting. Finally, the Bioinformatics Core (Aim 4) will be responsible for managing databases of integrated clinical and experimental data, and provide bioinformatic support to whole genome/exome studies (Proj. 1, Aim 2), whole transcriptome sequencing studies (Proj. 2, Aim 1 &3), biomarker validation (Proj. 2, Aim 1), validation of cell-based xenografts (Proj. 3, Aim 2), evaluation of AAV and morpholino antisense drugs (Proj.
2 Aim 3 and Proj.
3 Aims 1 &2) and developmental screening for DUX4 target genes (Proj. 3, Aim 4).

Public Health Relevance

The functions of Cell Core C are vital to the Center, providing both biomaterials and bioinformatic support to all projects. In addition to supporting Center investigators. Cell Core C distributes characterized primary FSHD and control muscle cells to labs performing FSHD or other muscular dystrophy research.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD060848-08
Application #
8734468
Study Section
Special Emphasis Panel (ZNS1-SRB-S)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
8
Fiscal Year
2014
Total Cost
$376,268
Indirect Cost
$122,237
Name
University of Massachusetts Medical School Worcester
Department
Type
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
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Wallace, Lindsay M; Saad, Nizar Y; Pyne, Nettie K et al. (2018) Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD. Mol Ther Methods Clin Dev 8:121-130
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Shaw, Natalie D; Brand, Harrison; Kupchinsky, Zachary A et al. (2017) SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome. Nat Genet 49:238-248
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Chen, Jennifer Cj; King, Oliver D; Zhang, Yuanfan et al. (2016) Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics. Mol Ther 24:1405-11
Ansseau, Eugénie; Eidahl, Jocelyn O; Lancelot, Céline et al. (2016) Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation. PLoS One 11:e0146893

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