E/Prof Miranda Grounds
Senior Honorary Research Fellow
Anatomy, Physiology and Human Biology, School of
- Contact details
- School of Anatomy, Physiology and Human Biology
The University of Western Australia (M309)
35 Stirling Highway
CRAWLEY WA 6009
- +61 8 6488 3486
- +61 8 6488 1051
- Personal homepage
- BSc W.Aust., PhD Lond.
- For over 30 years, the research of M Grounds has focussed on factors controlling the repair of damaged skeletal muscle and on potential treatments for muscle diseases such as Duchenne’s muscular dystrophy and muscle wasting, with a focus on in vivo studies and tissue analyses. Her research has pioneered many studies into factors controlling skeletal muscle regeneration with a particular emphasis on myogenesis in post-natal skeletal muscle in vivo, and an ongoing interest in the role of the extracellular matrix. Research on cell therapies developed the Y-chromosome probe for tracking male nuclei and identified the massive and rapid death of injected donor cells in Myoblast Transfer Therapy. Other projects investigate stem cell therapies (MG published the first bone-marrow reconstitution experiments to look for bone-marrow derived muscle stem cells in 1983) and Tissue Engineering for skeletal and cardiac muscle. Current research includes the in vivo role of IGF-1 isoforms, a focus on inflammation and anti-cytokine therapies, metabolism, and oxidative stress, all with applications to skeletal muscle wasting with ageing, muscular dystrophy and especially age-related loss of muscle mass and function (Sarcopenia).
- Key research
- Skeletal muscle repair; the role of growth factors and extracellular matrix components; Muscular Dystrophy; ageing; Cell and gene therapy for muscle diseases; inflammation and oxidative stress.
- MG has over 150 publications. Last five years are detailed below. Impact Factors and Citations are current to April 2011.
Scholarly book chapters
1.McMahon C, Shavlakadze T, Grounds MD. (2011) Role of IGF-I in age-related loss of skeletal muscle mass and function. In Sarcopenia - Age-Related Muscle Wasting and Weakness (Ed. Lynch GS), Springer. pp393-418.
2.Grounds MD, Relaix F. (2010) Myogenic Precursor Cells in Section I- Scientific basis of muscle disease in 8th Edition of Disorders of Voluntary Muscles (Eds Hilton-Jones D, Griggs RC, Bushby K and Karpati G.) Cambridge University Press. Chapter 2, pp20-36.
3.Grounds MD. (2008) Complexity of Extracellular Matrix and Skeletal Muscle Regeneration. In Skeletal Muscle Repair and Regeneration (Ed S Schiaffino and TA Partridge), Springer: Chapter 13. pp269-302.
Refereed journal articles
4.Prêle CM, Reichelt ME, Mutsaers SE, Davies M, Delbridge LM, Headrick JP, Rosenthal N, Bogoyevitch MA, Grounds MD. (2011) Insulin-like growth factor-1 overexpression in cardiomyocytes diminishes ex vivo heart functional recovery after acute ischemia. Cardiovascular Pathology Jan 24 (online). (IF:1.626)
5.Grounds MD, Shavlakadze T. (2011) Impact of growth on sarcolemma properties. Scientific and clinical implications in skeletal muscles for molecular dynamics, cellular responses, experimental models, therapies and manifestation of muscle disorders. Bioessays. Accepted (Feb). (IF:5.125)
6.Piers AT, Lavin T, Radley-Crabb H, Bakker AJ, Grounds MD, Pinniger GJ. (2011) Blockade of TNF in vivo (using cV1q antibody) reduces contractile dysfunction of skeletal muscle in response to eccentric exercise in dystrophic mdx and normal mice. Neuromuscular Disorders Feb;21(2):132-141. (IF:2.977)
7.Shavlakadze T, Grounds MD. (2010) IGF-1 is a major regulator of muscle mass during growth but not for adult myofibre hypertrophy. (Comment on Point:counter-point IGF is/is not the major physiological regulator of muscle mass). J of Applied Physiology Jun;108(6):1829. (IF:3.732)
8.Shavlakadze T, Chai R, Maley K, Cozens G, Winn N, Rosenthal N, Grounds G, Grounds M. (2010). A growth stimulus is needed for IGF-1 to induce skeletal muscle hypertrophy in vivo. J Cell Science Mar 15;123(Pt 6):960-71. (IF:6.144)(5 citations)
9.Shavlakadze T, McGeachie J, Grounds MD. (2010) Delayed but excellent myogenic stem cell response of regenerating skeletal muscles in geriatric mice. Biogerontology Jun;11(3):363-76. (IF:2.816)(4)
10.Waters F, Shavlakadze T, McIldowie MJ, Piggott MJ, Grounds MD. (2010) Use of pifithrin to inhibit p53 mediated signalling of TNF in dystrophic muscles of mdx mice. Molecular and Cellular Biochemistry 337:119-131. (IF:1.896)(1)
11.Ridgley JA, Pinniger GJ, Hamer P, Grounds MD. (2009) The physiological effects of IGF-1 (Class 1Ea transgene) over-expression on exercise-induced damage and adaptation in dystrophic skeletal muscles of mdx mice. Pflugers Archiv –Eur. J Physiol 457(5):1121-32. (IF:3.695)(1)
12.Arthur P, Grounds MD, Shavlakadze T. (2008) Oxidative stress as a therapeutic target during muscle wasting: considering the complex interactions. Current Opinions in Clinical Nutrition and Metabolic Care 11:408-416. (IF:4.291)(9)
13.Grounds MD, Radley H, Lynch GS, Nagaraju K, De Luca A. (2008) Towards developing standard operating procedures for pre-clinical testing in the mdx mouse model of Duchenne Muscular Dystrophy. Neurobiology of Disease. 31:1-19. (IF:4.518)(26)
14.Grounds MD (2008) Two tiered hypotheses for Duchenne Muscular Dystrophy Visions and Reflections in Cellular and Molecular Life Sciences (CMLS). 65(11):1621-5. (IF:6.09)(6)
15.Smythe G, Shavlakadze T, Roberts P, Davies MJ, McGeachie JK, Grounds MD., (2008) Age influences the early events of skeletal muscle regeneration: studies of whole muscle grafts transplanted between young (2 month) and old (13-21 months) mice. Experimental Gerontology 43: 550-562. (IF:3.342)(11)
16.Klyen BR, Armstrong JJ, Adie SG, Radley HG, Grounds MD, Sampson DD. (2008) Three-dimensional optical coherence tomography of whole muscle autografts as a precursor to morphological assessment of muscular dystrophy in mice. J. Biomedical Optics. Jan-Feb.13(1):011003. (IF:2.501)(1)
17.Grounds MD, Radley H, Gebski B, Bogoyevitch, M, Shavlakadze TS. (2008) Implications of cross-talk between TNFa and IGF-1 signalling in skeletal muscle. Clinical and Experimental Pharmacology and Physiology. 35: 846–851. (IF:1.936)(14)
18.Radley H, Davies M, Grounds MD. (2008) Reduced muscle necrosis and long-term benefits of cV1q (anti-mouse TNF-alpha) antibody treatment in dystrophic mdx mice. Neuromuscular Disorders. 18(3): 227 – 238. (IF:2.977)(18)
19.Schertzer JD, van der Poel C, Shavlakadze T, Grounds MD, Lynch GS. (2008) Muscle specific overexpression of IGF-I improves E-C coupling in skeletal muscle fibers from dystrophic mdx mice. Am J Physiol Cell Physiol. 294:C161–C168. (IF 4.013)(6)
20.Ng DCH, Gebski B, Grounds MD, Bogoyevitch M. (2008) Myoseverin disrupts sarcomeric organization in myocytes: an effect independent of microtubule assembly inhibition. Cell Motility and the Cytoskeleton. 65: 40–58. (IF:2.840)(1)
21.White JD, Vuocolo T, McDonagh M, Grounds MD, Harper G, Cockett NE, Tellam R. (2008) Cellular analysis of the Callipyge phenotype through skeletal muscle development; association of Dlk1 with developing satillite cells. Differentiation. 76:283-298. (IF:3.311)(11)
22.Davies KE, Grounds MD. (2007) Modified patient stem cells as prelude to autologous treatment of muscular dystrophy Cell Stem Cell 1:595-6. (IF:23.563)(2)
23.Grounds MD, Davies KE. (2007) The allure of stem cell therapy for muscular dystrophy. Neuromuscular Disorders 17(3):206-208. (IF:2.977)(9)
24.Radley H, De Luca A, Lynch GS, Grounds MD. (2007) Duchenne Muscular Dystrophy: focus on pharmaceutical and nutritional interventions. International Journal of Biochemistry and Cell Biology. 39(3):469-77. (IF:4.887)(26)
25.Davies KE, Grounds MD. (2006) Treating muscular dystrophy with stem cells? Cell. 127 (7):1304-6. (IF:31.152)(10)
26.Shavlakadze T, Grounds MD. (2006) Of bears, meat, mice and men: complexity of factors affecting skeletal muscle mass and fat. BioEssays 28(10): 994-1009. (IF:5.125)(23)
27.Hodgetts, S, Radley, H, Davies M, Grounds MD. (2006) Reduced necrosis of dystrophic muscle by depletion of host neutrophils, or blocking TNFa function with Etanercept in mdx mice. Neuromuscular Disorders 16 591-602. (IF:2.977)(44)
28.Han R, Grounds MD, Bakker AJ. (2006) Measurement of sub-membrane [Ca2+] in adult myofibers and cytosolic [Ca2+] in myotubes from normal and mdx mice using the Ca2+ indicator FFP-18. Cell Calcium 40(2006) 299-307. (IF:4.288)(12)
29.Radley H, Grounds MD. (2006) Cromolyn administration (to block mast cell degranulation) reduces necrosis of dystrophic muscle in mdx mice. Neurobiology of Disease 23(2006) 387-397. (IF:4.518) (23)
30.Shavlakadze T, White JD, Davies M, Grounds MD, Boswell JM, Burt DW, Asante EA, Tomas FM, Goddard C. (2006) Rskα-actin/hIGF-I transgenic mice with increased IGF-I levels in skeletal muscle and blood: impact on regeneration, denervation, atrophy and muscular dystrophy. Growth Hormone and IGF Research Jun;16(3):157-73. (IF: 2.352)(10)
- Roles, responsibilities and expertise
- Prof Miranda Grounds (MG) with a BSc(Hons) from the University of Western Australia (UWA) and PhD from the University of London (1978), obtained her first NH&MRC grant in 1980 and in 1994 became an NH&MRC Senior Research Fellow and Professor in the School of Anatomy and Human Biology, UWA. For over 30 years, the research of MG has focussed on factors controlling damage and repair of skeletal muscle and on potential treatments for muscle diseases, with a strong focus on in vivo studies and tissue analyses. Some ‘firsts’ include the first bone- marrow reconstitution study to test for circulating myogenic stem cells (1983), use of autoradiography to test and challenge the tissue culture quantal mitosis theory in vivo (1987) and document kinetics of myogenesis in damaged adult muscle in vivo (1985-1992), development of the Y-chromosome probe to visualise and quantitate male mouse cells (1991-) and describe massive rapid loss of cultured donor myoblasts in vivo (1996). MG has over 150 publications, 20 since 2008, with strong citations: H-Factor = 37 (March 2011, Citation sum is 3995 and Av./item is 25.05). The research covers diverse areas including; Muscle regeneration, Stem cells; Myoblast Transfer Therapy and other therapies for Muscular Dystrophies; Muscle hypertrophy and atrophy; plus Ageing (6 related papers and reviews since 1998). Recent research has focussed on factors controlling the maintenance of muscle mass and function into old age.
Since 2000, MG has supervised 16 PhD students (9 are current) and over 20 Honours students (12 with 1st class). MG has organised numerous conferences, is a reviewer for many international funding agencies and journals, and serves on Editorial and various other Boards and committees including: Board of the International Society of Differentiation since 2006 and, since 2010, Member of the Fundamental Myology commission of the Association contre les Myopathies (AFM) Scientific Council, plus Member of the TREAT-NMD Advisory Committee for Therapeutics (TACT) (these involve fully paid trips each year). In 2005 MG received an Excellence in Postgraduate Supervision Award, UWA and was the recipient of the Barry Preston Award from the Matrix Biology Society of Australia and New Zealand; in 2012, MG will present the prestigious Mauro lecture at the 2012 international Satellite Cell meeting (the first female to receive this honour).
These research achievements are widely recognized internationally as evidenced by invited reviews/Chapters and also overseas grants, and MG has obtained about $10.5 million in funding. International recognition is also demonstrated by many invitations for MG to speak at national/international conferences/workshops (>100 since 1980),with 12 fully paid international invitations since 2010. Some recent relevant invitations are: 2005 ●FASEB Skeletal muscle satellite and stem cells. USA; ●Translational Medicine for skeletal muscle biology, Sweden; ●Novartis Muscle Workshop, Switzerland. 2007 ●Workshop (NIH): Pre-clinical testing for Duchenne dystrophy, USA. ●Keynote: Medical Sciences Congress, New Zealand, ●Stem Cell Therapy for Skeletal Muscle Myopathies, France. ●Plenary: 4th Cachexia Conference, Florida, USA 2008 ●Bispebjerg Symposium on Sports Medicine, Denmark 2009 ●Workshop: Programs specifying muscle identity, with a possible link to disease, France ●Workshop: Current bottlenecks in translational medicine in inherited neuromuscular diseases (Treat-NMD/NIH), Belgium. 2010 ●Gage Conference on Muscle, Canberra, Australia ●Muscle Satellite Symposium, Queenstown Molecular Biology, New Zealand. ●Jain Foundation, Seattle, USA. ●16th Intl Soc. Differentiation, Japan. 2011 ● Myology 2011 (AFM), Lille, France, ●Gordon Conference, New Horizons for Myogenesis, Therapies for Aging and Dystrophy, USA. (plus invited talk at EU MyoAGE meeting, Finland) 2012 ●MG will present the 7th Mauro lecture at the 2012 Satellite Cell meeting, Italy.
- Funding received
- Medical Health and Research Infrastructure Fund.
The International Parent Project.
Association Francaise contre les Myopathies.
Muscular Dystrophy Association of America 2000.
Heart Foundation, Australia.
Meat & Livestock, Australia.
National Health and Medical Research Council of Australia.
The Arnold Yeldham and Mary Raine Medical Research Foundation,UWA.
Medical Research Council of W.A.
- Committees and Conference organisation.
MG has been extensively involved in organisation of about 20 Conferences. Two major initiatives that have resulted in ongoing conferences were:
Initiating (and joint Convenor with George Yeoh) of the Combined Biological Sciences conference in 1990. This is now a major annual meeting in Perth.
Member of international Steering committee for a new meeting on “Satellite cells, regeneration and skeletal muscle diseases” 1998, in Boston. Now a regular event.
Some recent Conference and Symposia organisation is indicated below.
2000 Organiser for major TERC meeting "Frontiers in Tissue Engineering: West Australian Symposium", University of Western Australia, October, 2000.
2001 Organiser “The Cottesloe Beach Muscle Symposium”, Perth, Sept 2001.
2002 Organiser for TERC “Stem cell and Tissue Engineering Symposium”, Perth, November 2002.
2002-2007 Organiser for series of “Molecular Mechanisms of Development” Conferences, Perth. 2004 Organising Committee: Matrix Biology Society of Australia & New Zealand meeting, Rottnest, WA, Sept 2004.
2003-2004 Co-Chair of programme committee for COMBIO 2004, Perth, September 2004.
2005- Organising Committee: Austr. Neuroscience Soc. Conference, Perth, Feb 2005.
2006 Organising Committee: Focus on Microscopy, Perth, April 2006.
Membership of Societies
Australian and New Zealand Society for Cell & Developmental Biology (ANZSCDBI). President of ANZSCDB from 1996-1998; Australian Society for Medical Research (ASMR); Australian Society for Biochemistry & Molecular Biology (ASBMB); Matrix Biology; World Muscle Society; Tissue Engineering Society International.
Membership of Boards: serves on 3 journal Editorial Boards; J Meat & Livestock (Australia) Scientific Advisory Board (2002-2009) plus Sheep Functional Genomics Program Consultative Committee (2003-2009); Bioheart (USA Company) Scientific Advisory Board (2003-); Norwegian Parent Project Advisory Committee (2006-); International Society of Differentiation Board Member (2006- )
- Honours and awards
- 2005 - UWA Excellence in Postgraduate Supervision Award.
2005 - Matrix Biology Society of Australia and New Zealand. Barry Preston Award (the annual Society medal).
- Previous positions
- 1994-1998 Senior Research Fellow (NHMRC), UWA.
1980-1994 Senior Research Officer (NHMRC), UWA.
1978-1980 Research Officer, UWA.
1975-1978 Research Biochemist, Charing Cross Hospital, London.
1972-1974 Research Assistant, UWA.
- New and noteworthy
- The research over 30 years has provided many pioneering studies in the general area of regeneration of adult skeletal muscle and therapies for muscular dystrophy. Some ‘firsts’ include the first bone- marrow reconstitution study to test for circulating myogenic stem cells (1983[28 citations]) about 15 years before this topic became fashionable, with a sustained current interest in myogenic stem cells: many researchers now generally agree with the conclusions of this early paper. Use of in vivo autoradiography tested and caused the demise of the tissue culture quantal mitosis theory (1987) and documented kinetics of myoblast proliferation during myogenesis in damaged adult muscle in vivo (1985-1992 e.g 1987). Demonstration by electron microscopy of new plasmalemma formation after damage and myogenic fusion in vivo (1990 & ). Identification of muscle precursor cells in vivo by use of MyoD1 and myogenin probes (1992). Many studies of the role of inflammation in regeneration (e.g 1993). Development of the mouse Y-chromosome probe as a new marker to visualise and quantitate transplanted male mouse cells (1991-) and describe massive rapid loss of cultured donor myoblasts in vivo (1996) as well as quantification of such cell death – then widely used as a cell marker internationally. First report that blockade of TNF reduces the severity of muscular dystrophy (2004). Many studies of transgenic over-expression of IGF-1 in muscles that challenge established views (2004 and 2005). Many reviews have received high citations e.g on regeneration (1991[234 & 1999), muscular dystrophy (2008), myogenic stem cells (2002) and ageing (1998 & 2002). Activities in all of these areas (and more) continue unabated as outlined for publications in the last 5 years.
- Current projects
- Jain Foundation: Monitoring & Reducing Oxidative Stress Associated with Dystropathology in Dysferlin Deficient Mice. Funds Approved $57,752.82
Medical Health and Research Infrastructure Fund Round 14 (2010). Funds Approved $35,149.00
NHMRC 2009-2011: Role of IGF-1 in skeletal muscle hypertrophy and atrophy. Funds Approved $379,500.00