• Patients & Families
• Education
• Research
• Community

• Referring Physicians
• Find a Physician
• Departments & Centers
• About URMC

• Libraries
• Alumni
• Giving

URMC » Fields Center

• Fields Center Home
  • Meet the Investigators
  • Scientific Advisory Board
  • Collaborators
  • Related Links
  • Contact Us
• Scientific Projects
• In the Spotlight
• Information for Patients and Families
• Information for Researchers
  • Scientific References
  • Protocols and Procedures
• Volunteer for a Study
• Make a Gift

Scientific Projects

Current Fields Center projects are focused on the following areas of FSHD (FSH dystrophy) 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.

van der Maarel SM, Tawil R, Tapscott SJ. Facioscapulohumeral muscular dystrophy and DUX4: breaking the silence. Trends Mol Med. 2011 Jan 31. [Epub ahead of print] PMID: 21288772 [PubMed - as supplied by publisher]

Snider L, Geng LN, Lemmers RJ, Kyba M, Ware CB, Nelson AM, Tawil R, Filippova GN, van der Maarel SM, Tapscott SJ, Miller DG. Facioscapulohumeral dystrophy: incomplete suppression of a retrotransposed gene. PLoS Genet. 2010 Oct 28;6(10):e1001181.

de Greef JC, Lemmers RJ, Camaño P, Day JW, Sacconi S, Dunand M, van Engelen BG, Kiuru-Enari S, Padberg GW, Rosa AL, Desnuelle C, Spuler S, Tarnopolsky M, Venance SL, Frants RR, van der Maarel SM, Tawil R. Clinical features of facioscapulohumeral muscular dystrophy 2. Neurology. 2010 Oct 26;75(17):1548-54. PMID: 20975055 [PubMed - in process]

Lemmers RJ, van der Vliet PJ, Klooster R, Sacconi S, Camaño P, Dauwerse JG, Snider L, Straasheijm KR, Jan van Ommen G, Padberg GW, Miller DG, Tapscott SJ, Tawil R, Frants RR, van der Maarel SM. A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy. Science. 2010 Aug 19. [Epub ahead of print] PMID: 20724583 [PubMed - as supplied by publisher]

Tsumagari K, Chen D, Hackman JR, Bossler AD, Ehrlich M.FSH dystrophy and a subtelomeric 4q haplotype: a new assay and associations with disease. J Med Genet. 2010 Aug 15. [Epub ahead of print] PMID: 20710047 [PubMed - as supplied by publisher]

Tawil R, van der Maarel S, Padberg GW, van Engelen BG. 171st ENMC international workshop: Standards of care and management of facioscapulohumeral muscular dystrophy. Neuromuscul Disord. 2010 Jul;20(7):471-5. No abstract available. PMID: 20554202 [PubMed - indexed for MEDLINE

Lemmers RJ, van der Vliet PJ, van der Gaag KJ, Zuniga S, Frants RR, de Knijff P, van der Maarel SM. Worldwide population analysis of the 4q and 10q subtelomeres identifies only four discrete interchromosomal sequence transfers in human evolution. Am J Hum Genet. 2010 Mar 12;86(3):364-77. Epub 2010 Mar 4. PMID: 20206332 [PubMed - in process] 

Xu X, Tsumagari K, Sowden J, Tawil R, Boyle AP, Song L, Furey TS, Crawford GE, Ehrlich M. DNaseI hypersensitivity at gene-poor, FSH dystrophy-linked 4q35.2. Nucleic Acids Res. 2009 Dec;37(22):7381-93. [Epub ahead of print] PMID: 19820107 [PubMed - as supplied by publisher]

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