Scientific Projects
Current Fields Center projects are focused on the following areas of FSHD research:
CLINICAL RESEARCH:
- Clinical Care: Develop clinical practice guidelines for the care of individuals with FSHD. These practice guidelines will deal with issues such as genetic testing, physical therapy, exercise, bracing, scapular surgery and potential retinal and respiratory complications of FSHD. The guidelines will help standardize the care of patients with FSHD across the world.
- Clincal Trials Readiness: Develop consensus on the best outcome measures for future FSHD clinical trials. As part of this effort, we are developing a disease-specific, patient-determined outcome measure.
BASIC AND TRANSLATIONAL RESEARCH:
- Development of Biological Resources: Collect DNA, muscle and skin biopsy samples from individuals with FSHD who are carefully characterised to allow for accurate correlation of the clinical manifestations with changes observed in the DNA and tissue samples. Tissue resources generated include muscle biopsy samples, myoblasts cell lines, fibroblast cell lines as well as the creation of immortalized myoblasts..
- Detailed genotyping of patients with FSHD: This allows the identification of rare kindreds with unsual large deletions extending outside of the known D4Z4 repeat area allowing a better understanding of the minimal region of 4q35 necessary to cause FSHD. Additionally, detailed genotyping will allow the identification of unique DNA sequences within the distal part of of 4q35 necessary for the development of FSHD.
- Indentification of the underlying pathophysiology of FSHD: Several projects are underway within the Fields Center and in collaborative studies to identify the molecular pathphysiology of FSHD. The current emphasis, based on findings from recent studies, is on investigating the role of DUX4 expression in FSHD.
- Identification of therapeutic targets for FSHD: Finding effective treatments for patients with FSHD is the ultimate target of the Fields Center. To that end, we are well positioned, given our resources, to develop models test our candidate molecular mechanisms and to develop assays for for drug screening.
Scientific Publications
The following is a list of Scientific publications of studies performed by the Fields Center investigators.
Masny PS, Chan OY, de Greef JC, Bengtsson U, Ehrlich M, Tawil R, Lock LF, Hewitt JE, Stocksdale J, Martin JH, van der Maarel SM, Winokur ST. Analysis of allele-specific RNA transcription in FSHD by RNA-DNA FISH in single myonuclei. Eur J Hum Genet. 2009 Nov 4. [Epub ahead of print] PMID: 19888305 [PubMed - as supplied by publisher]
Zeng W, de Greef JC, Chen YY, Chien R, Kong X, Gregson HC, Winokur ST, Pyle A, Robertson KD, Schmiesing JA, Kimonis VE, Balog J, Frants RR, Ball AR Jr, Lock LF, Donovan PJ, van der Maarel SM, Yokomori K. Specific loss of histone H3 lysine 9 trimethylation and HP1gamma/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD). PLoS Genet. 2009 Jul;5(7):e1000559. Epub 2009 Jul 10. PMID: 19593370
de Greef JC, Lemmers RJ, van Engelen BG, Sacconi S, Venance SL, Frants RR, Tawil R, van der Maarel SM. Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD. Hum Mutat. 2009 Jul 14. [Epub ahead of print] PMID: 19728363 [PubMed - as supplied by publisher]
Snider L, Asawachaicharn A, Tyler AE, Geng LN, Petek LM, Maves L, Miller DG, Lemmers RJ, Winokur ST, Tawil R, van der Maarel SM, Filippova GN, Tapscott SJ. RNA Transcripts, miRNA-sized Fragments, and Proteins Produced from D4Z4 Units: New Candidates for the Pathophysiology of Facioscapulohumeral Dystrophy. Hum Mol Genet. 2009 Apr 9. [Epub ahead of print] PMID: 19359275
Klooster R, Straasheijm K, Shah B, Sowden J, Frants R, Thornton C, Tawil R, van der Maarel S.Comprehensive expression analysis of FSHD candidate genes at the mRNA and protein level. Eur J Hum Genet. 2009 Oct 7. [Epub ahead of print] PMID: 19809486 [PubMed - as supplied by publisher]
Tawil R. Facioscapulohumeral muscular dystrophy. Neurotherapeutics. 2008; 5(4):601-6. PMID: 19019312
de Greef JC, Frants RR, van der Maarel SM. Epigenetic mechanisms of facioscapulohumeral muscular dystrophy. Mutat Res. 2008 Aug 3. [Epub ahead of print] PMID: 18723032
van der Maarel SM. Epigenetic mechanisms in health and disease. Ann Rhem Dis. 2008. PMID: 19022824
For more information, please contact the Fields Center FieldsCenter@urmc.rochester.edu
