Meagan Mcgrath

Dr

  • 23 Innovation Walk, 77

    Australia

19992019
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Personal profile

Biography

Meagan works in the Faculty of Medicine, Nursing and Health Sciences at Monash University as a Research Fellow.

Biography

I am a senior-postdoctoral researcher in the laboratory of Professor Christina Mitchell, Monash University, Clayton, Australia. For the past 13 years I have been head of the Skeletal Muscle Research Group within Professor Mitchell's laboratory. Together with Professor Mitchell I oversee all research projects in this area, manage the daily research activities, co-supervise students, prepare manuscripts for publication and present research findings at conferences.

I currently have three priority research areas:

The first is to identify basic pathways that are required for skeletal muscle development or to maintain normal skeletal muscle homeostasis. Our particular focus in this area, is the discovery of new genes that control myogenesis and also autophagy.

The second area is to identify novel skeletal muscle disease pathways. This work is focused on the heterogeneous group of inherited skeletal muscle diseases called muscular dystrophies or myopathies. Our work involves identifying new disease genes and we employ the CRISPR/Cas9 gene-editing strategy to develop knockout or knock-in mouse lines to model these disorders. In combined use with our muscle cell culture disease models, we aim to map in detail the precise disease mechanisms.

The third area is to identify new therapeutic targets for skeletal muscle diseases and can undertake pre-clinical testing of drugable targets using our available mouse models.

Specific Research Expertise:

I have research experience in the following skeletal muscle diseses; Duchenne muscular dystrophy, Facioscapulohumeral muscular dystrophy and congential muscular dystrohy. One of my key research focuses for almost two decades has been the FHL family of LIM proteins which are highly expressed in skeletal muscle. I have undertaken extensive characterization of FHL1 protein function in skeletal muscle. My most important contribution was to participate in the identification of FHL1 gene mutations as the cause of both skeletal and cardiac muscle disease. Our collaborative study identifying FHL1 mutations in patients with Reducing Body Myopathy solved a 40 year enigma as to cause of this fatal disease. This seminal discovery of  FHL1 gene mutations, has led to way to the identification of a further 6 muscle diseases caused by FHL1 mutations (collectively termed "FHL1 myopathies"). Our current focus is to determine precisely how FHL1 mutations cause muscle disease and why this results in a broad clinical spectrum. My work in this area has been very highly cited and I am amongst leading experts in this field. I have been an invited speaker at national (eg. GAGE muscle conference) and international (eg. European Neuromuscular Centre Workshop) conferences  to discuss my work in this area and my review article on FHL1 myopathies has been highly cited by the broader research and clinical community  (Cowling BS, 2011 , Neuromuscul Disord, 21(4): 237-51, 57 citations).

My more recent work has centred on the role of autophagy in skeletal muscle disease.  The identification of autophagy defects as an underlying disease mechanism, is at the current forefront of neuromuscular disease research. We have identified a new disease process in skeletal muscle, involving defects in a previously unexplored component of the autophagy pathway. Our future work is aimed at identifying the precise regulatory proteins involved in this novel autophagy process and how these impact human muscle disease.  

 

 

 

 

 

 

 

 

 

 

Research area keywords

  • Skeletal muscle
  • Dystrophy
  • Myopathy
  • Myogenesis
  • autophagy
  • FHL1

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Projects 2000 2019

Research Output 1999 2015

FHL1 reduces dystrophy in transgenic mice overexpressing FSHD muscular dystrophy region gene 1 (FRG1)

Feeney, S. J., Mcgrath, M. J., Sriratana, A., Gehrig, S. M., Lynch, G. S., D'Arcy, C. E., Price, J. T., McLean, C. A., Tupler, R. & Mitchell, C. A., 19 Feb 2015, In : PLoS ONE. 10, 2, 29 p., e0117665.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File

X-linked recessive distal myopathy with hypertrophic cardiomyopathy caused by a novel mutation in the FHL1 gene

D'Arcy, C. E., Kanellakis, V., Forbes, R., Wilding, B., Mcgrath, M. J., Howell, K. B., Ryan, M. M. & McLean, C. A., 2015, In : Journal of Child Neurology. 30, 9, p. 1211 - 1217 7 p.

Research output: Contribution to journalArticleResearchpeer-review

199th ENMC international workshop: FHL1 related myopathies, June 7-9, 2013, Naarden, The Netherlands

Bertrand, A. T., Bonnemann, C. G., Bonne, G., Mitchell, C. A. & Mcgrath, M. J., 2014, In : Neuromuscular Disorders. 24, 5, p. 453 - 462 10 p.

Research output: Contribution to journalArticleOther

Open Access
File

FHL1 mutants that cause clinically distinct human myopathies form protein aggregates and impair myoblast differentiation

Wilding, B. R., Mcgrath, M. J., Bonne, G. & Mitchell, C. A., 2014, In : Journal of Cell Science. 127, 10, p. 2269 - 2281 13 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File

Identification of FHL1 as a therapeutic target for Duchenne muscular dystrophy

D'Arcy, C. E., Feeney, S. J., McLean, C. A., Gehrig, S. M., Lynch, G. S., Smith, J. E., Cowling, B. S., Mitchell, C. A. & Mcgrath, M. J., 2014, In : Human Molecular Genetics. 23, 3, p. 618 - 636 19 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File