Dr Gina Ravenscroft BSc (Hons), PhD Gina Ravenscroft


Team Leader of Foetal Akinesias and Muscle Pathobiology
Neurogenetic Diseases

T:  +61 8 6151 0740
E:  gina.ravenscroft@uwa.edu.au
 

Dr Gina Ravenscroft is a postdoctoral researcher and current recipient of an Australian National Health and Medical Research Council Early Career Fellowship, within the Neurogenetic Diseases Laboratory.  Gina joined Professor Laing’s laboratory as a PhD student after obtaining her undergraduate degree and Honours qualifications majoring in Physiology at UWA.

Research overview
Her main research interests include investigating the genetics and pathobiology of rare groups of neurogenetic diseases, including foetal akinesia, Strongman syndrome and paediatric cardiomyopathy.

Research projects
Foetal Akinesia

Gina and Professor Laing identified that there was an unmet need for disease gene discovery in a group of patients with very severe neuromuscular diseases that present in utero with abnormal movements (foetal akinesia).  Most of these patients do not survive to term or die in the early neonatal period. In a collaboration with neurologists, geneticists and pathologists from across Australia (including via the Australasian Neuromuscular Network) and overseas, Gina is collating a cohort of patients with foetal akinesia due to an underlying neuromuscular condition without a genetic diagnosis. In just a short time, this cohort has increased to over 160 cases from more than 130 unrelated families from Australia, France, Germany, Honk Kong, Iran, Italy, Turkey and the United Kingdom. The team is currently using traditional and next generation sequencing technologies to identify the causative disease genes in this cohort; the associated pathogenesis is also been investigated. To date, five novel disease genes have been identified within this cohort (including KLHL40 and KLHL41 which are both published). This research is currently funded by a Project Grant from the NHMRC, the French Muscular Dystrophy Association (AFM), and the Liuzzi Foundation and is a focus of Ms Sarah Beecroft’s PhD candidature.

Strongman Syndrome
Gina is investigating Western Australian patients and families with similar phenotypes to families identified in the French Canadian population by Professor Bernard Brais (McGill University, Montreal). Gina and Professor Brais are using traditional and next generation sequencing technologies to identify the genetic basis of the conditions in these families. This research is currently funded by a Project Grant from the NHMRC.

Paediatric cardiomyopathy
Gina is also investigating Turkish patients with paediatric cardiomyopathy. This collaboration has budded from the collaborations Gina has had with Turkish clinicians on foetal akinesia families. The strength of the Turkish paediatric cardiomyopathy cohort is the high percentage of consanguineous cases which should facilitate discovery of the causative recessive mutations.

Muscle Pathobiology
Gina has investigated the pathobiology of some of the disease genes she has identified using the skill set in muscle physiology and skeletal muscle culture that she obtained during her Honours degree in Physiology and her PhD. She has also used this skill set on the animal models we have developed to investigate the pathobiology of the skeletal muscle actin diseases and the proof of principle that cardiac actin can be used to treat skeletal muscle actin diseases.

Her current focus for this research is investigating the pathobiology of the candidate novel disease genes she has identified and in assessing the Group’s investigation of clinically applicable therapies for the skeletal muscle actin diseases, particularly investigating the use of viral gene therapy to deliver normal actin genes to the mouse models of both dominant and recessive skeletal muscle alpha-actin diseases.  The muscle pathobiology research is funded by the NHMRC, the Association Francaise contre les Myopathies and A Foundation Building Strength for Nemaline Myopathy.

Selected publications

  1. Zaharieva, I. T., M. G. Thor, E. C. Oates, C. van Karnebeek, G. Hendson, E. Blom, N. Witting, M. Rasmussen, M. T. Gabbett, G. Ravenscroft, M. Sframeli, K. Suetterlin, A. Sarkozy, L. D'Argenzio, L. Hartley, E. Matthews, M. Pitt, J. Vissing, M. Ballegaard, C. Krarup, A. Slordahl, H. Halvorsen, X. C. Ye, L. H. Zhang, N. Lokken, U. Werlauff, M. Abdelsayed, M. R. Davis, L. Feng, R. Phadke, C. A. Sewry, J. E. Morgan, N. G. Laing, H. Vallance, P. Ruben, M. G. Hanna, S. Lewis, E. J. Kamsteeg, R. Mannikko and F. Muntoni (2016). "Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy." Brain 139(Pt 3): 674-691 [IF 9.1] [NCBI PubMed Entry]
  2. Ravenscroft, G., F. Nolent, S. Rajagopalan, A. M. Meireles, K. J. Paavola, D. Gaillard, E. Alanio, M. Buckland, S. Arbuckle, M. Krivanek, J. Maluenda, S. Pannell, R. Gooding, R. W. Ong, R. J. Allcock, E. D. Carvalho, M. D. Carvalho, F. Kok, W. S. Talbot, J. Melki and N. G. Laing (2015). "Mutations of GPR126 Are Responsible for Severe Arthrogryposis Multiplex Congenita." Am J Hum Genet 96(6): 955-961. [IF 10.9] [NCBI PubMed Entry]
  3. Ravenscroft, G., N. G. Laing and C. G. Bonnemann (2015). "Pathophysiological concepts in the congenital myopathies: blurring the boundaries, sharpening the focus." Brain 138(Pt 2): 246-268. [IF 10.2] [NCBI PubMed Entry]
  4. Yuen, M., S. A. Sandaradura, J. J. Dowling, A. S. Kostyukova, N. Moroz, K. G. Quinlan, V. L. Lehtokari, G. Ravenscroft, E. J. Todd, O. Ceyhan-Birsoy, D. S. Gokhin, J. Maluenda, M. Lek, F. Nolent, C. T. Pappas, S. M. Novak, A. D'Amico, E. Malfatti, B. P. Thomas, S. B. Gabriel, N. Gupta, M. J. Daly, B. Ilkovski, P. J. Houweling, A. E. Davidson, L. C. Swanson, C. A. Brownstein, V. A. Gupta, L. Medne, P. Shannon, N. Martin, D. P. Bick, A. Flisberg, E. Holmberg, P. Van den Bergh, P. Lapunzina, L. B. Waddell, D. D. Sloboda, E. Bertini, D. Chitayat, W. R. Telfer, A. Laquerriere, C. C. Gregorio, C. A. Ottenheijm, C. G. Bonnemann, K. Pelin, A. H. Beggs, Y. K. Hayashi, N. B. Romero, N. G. Laing, I. Nishino, C. Wallgren-Pettersson, J. Melki, V. M. Fowler, D. G. MacArthur, K. N. North and N. F. Clarke (2014). "Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy." J Clin Invest 124(11): 4693-4708. [IF 13.7[NCBI PubMed Entry]
  5. Gupta VA, Ravenscroft G, Shaheen R, Todd EJ, Swanson LC, Shiina M, Ogata K, Hsu C, Clarke N, Darras BT, Farrar MA, Hashem A, Manton ND, Muntoni F, North KN, Sandaradura SA, Nishino I, Hayashi YK, Sewry CA, Thompson EM,  Yau KS, Brownstein CA, Yu TW, Allcock RJN, Davis MR, Wallgren-Pettersson C, Matsumoto N, Alkuraya FS, Laing NG, Beggs AH. (2013) Identification of KLHL41 mutations implicates BTB-Kelch mediated ubiquitination as an alternative pathyway to myofibrillar disruption in nemaline myopathy. Am J Hum Genet 93(6): 1108-1117. [IF 11.2]. [NCBI PubMed Entry]
  6. Barnett CP, Todd EJ, Ong R, Davis MR, Atkinson V, Allcock R, Laing NG, Ravenscroft G. (2013) Distal Arthrogryposis type 5D with novel clinical features and compound heterozygous mutations in ECEL1. Am J Med Genet A. 164(7): 1846-1849. [IF 2.3]. [NCBI PubMed Entry]
  7. Ochala J, Iwamoto H, Ravenscroft G, Laing NG, Nowak KJ. (2013) Skeletal and cardiac actin isoforms differently modulate myosin cross-brdige formation and myofibre force production. Hum Mol Genet 22(21):4398-4404. [IF 7.7].  [NCBI PubMed Entry]
  8. Ravenscroft G, Miyatake S, Lehtokari VL, Todd EJ, Vornanen P, Yau KS, Hayashi YK, Miyake N, Tsurusaki Y, Doi H, Saitsu H, Osaka H, Yamashita S, Ohya T, Sakamoto Y, Koshimizu E, Imamura S, Yamashita M, Ogata K, Shiina M, Bryson-Richardson RJ, Vaz R, Ceyhan O, Brownstein CA, Swanson LC, Monnot S, Romero NB, Amthor H, Kresoje N, Sivadorai P, Kiraly-Borri C, Haliloglu G, Talim B, Orhan D, Kale G, Charles AK, Fabian VA, Davis MR, Lammens M, Sewry CA, Manzur A, Muntoni F, Clarke NF, North KN, Bertini E, Nevo Y, Willichowski E, Silberg IE, Topaloglu H, Beggs AH, Allcock RJ, Nishino I, Wallgren-Pettersson C, Matsumoto N, Laing NG. (2013) Mutations in KLHL40 Are a Frequent Cause of Severe Autosomal-Recessive Nemaline Myopathy. Am J Hum Genet 93:6-18. [IF 11.2].  [NCBI PubMed Entry]
  9. Ravenscroft G, McNamara E, Griffiths LM, Papadimitriou JM, Hardeman EC, Bakker AJ, Davies KE, Laing NG, Nowak KJ. (2013) Cardiac alpha-actin over-expression therapy in dominant ACTA1 disease. Hum Mol Genet 22(19):3987-97. [IF 7.7]. [Oxford Journals Entry]
  10. Ravenscroft, G., Thompson EM, Todd EJ, Yau KS, Kresoje N, Sivadorai P, Friend K, Riley K, Manton ND, Blumbergs P, Fietz M, Duff RM, Davis MR, Allcock RJ, Laing NG. (2013) Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations. Neuromuscul Disord 23:165-169. [IF 3.5]. [NCBI PubMed Entry]
  11. Ravenscroft, G. C. Jackaman, S. Bringans, J.M. Papadimitriou, L.M. Griffiths, E. McNamara, A.J. Bakker, K.E. Davies, N.G. Laing, and K.J. Nowak. (2011) Mouse models of dominant ACTA1 disease recapitulate human disease and provide insight into therapies. Brain 134:1101-1115. [IF: 9.5]. [NCBI PubMed Entry]
  12. Ravenscroft, G., E. Sollis, A.K. Charles, K.N. North, G. Baynam, N.G. Laing. (2011) Foetal akineisa – review of the genetics of the neuromuscular causes. J Med Genet 48:793-801. [IF 6.4]. [NCBI PubMed Entry]
  13. Ravenscroft, G., J.M. Wilmshurst, K. Pillay, P. Sivadorai, W. Wallefeld, K.J. Nowak, and N.G. Laing. 2011. A novel ACTA1 mutation resulting in a severe congenital myopathy with nemaline bodies, intranuclear rods and type I fibre predominance. Neuromuscul Disord 21:31-36. [IF: 2.8]. [NCBI PubMed Entry]
  14. Ravenscroft, G., K.J. Nowak, C. Jackaman, S. Clement, M.A. Lyons, S. Gallagher, A.J. Bakker, and N.G. Laing. (2007) Dissociated flexor digitorum brevis myofiber culture system--a more mature muscle culture system. Cell Motil Cytoskeleton 64:727-738. [IF: 2.5]. [NCBI PubMed Entry]
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