Abstract

Inclusion body myositis (IBM) is a disease of unknown cause characterized by slowly progressive painless weakness and with no effective treatment. It is one of a group of disorders known as inflammatory myopathies, in which some aspect of autoimmunity is believed to be prominent. IBM has been characterized as a disease in which there is accumulation of abnormal proteins. We propose detailed and large-scale studies of proteins in muscle in IBM and other inflammatory myopathies using powerful protein fractionation and mass spectrometry methods.
The specific aims are to look broadly at the profile of proteins present within muscle across the range of inflammatory myopathies;to attempt to purify insoluble protein aggregates from IBM muscle and characterize these aggregates by the use of mass spectrometry;and to correlate proteomic with microarray data.

Public Health Relevance

. Diseases of protein aggregation are important public health concerns and this research has the potential to further understand the nature of a disease in which protein aggregation is an important part of the mechanism. The technology developed in this proposal has relevance across a wide range of biomedical research.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS057225-02
Application #
7556776
Study Section
Skeletal Muscle and Exercise Physiology Study Section (SMEP)
Program Officer
Porter, John D
Project Start
2008-02-01
Project End
2011-07-31
Budget Start
2009-02-01
Budget End
2011-07-31
Support Year
2
Fiscal Year
2009
Total Cost
$226,535
Indirect Cost

  Institution

Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Greenberg, Steven A; Salajegheh, Mohammad; Judge, Daniel P et al. (2012) Etiology of limb girdle muscular dystrophy 1D/1E determined by laser capture microdissection proteomics. Ann Neurol 71:141-5
Greenberg, Steven A (2010) Type 1 interferons and myositis. Arthritis Res Ther 12 Suppl 1:S4
Salajegheh, Mohammad; Pinkus, Jack L; Amato, Anthony A et al. (2010) Permissive environment for B-cell maturation in myositis muscle in the absence of B-cell follicles. Muscle Nerve 42:576-83
Greenberg, Steven A (2010) Theories of the pathogenesis of inclusion body myositis. Curr Rheumatol Rep 12:221-8
Salajegheh, Mohammad; Kong, Sek Won; Pinkus, Jack L et al. (2010) Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy. Ann Neurol 67:53-63
Liao, Anne P; Salajegheh, Mohammad; Morehouse, Chris et al. (2010) Human plasmacytoid dendritic cell accumulation amplifies their type 1 interferon production. Clin Immunol 136:130-8
Greenberg, Steven A (2010) Dermatomyositis and type 1 interferons. Curr Rheumatol Rep 12:198-203
Greenberg, Steven A (2009) How citation distortions create unfounded authority: analysis of a citation network. BMJ 339:b2680
Salajegheh, Mohammad; Pinkus, Jack L; Taylor, J Paul et al. (2009) Sarcoplasmic redistribution of nuclear TDP-43 in inclusion body myositis. Muscle Nerve 40:19-31
Greenberg, Steven A (2009) Inflammatory myopathies: disease mechanisms. Curr Opin Neurol 22:516-23

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