Dr Antonios Matsakas is a senior lecturer in Biomedical Sciences at the Centre for Atherothrombotic and Metabolic Disease. He was awarded his PhD from the German Sport University Cologne in Tissue Morphology and Sports Medicine in 2004.
He received extensive post-doctoral training on skeletal muscle physiology at the Department of Anatomy and Physiology, The University of Padua (2005-2006) with Dr. C. Reggiani, at the School of Biological Sciences, The University of Reading (2007-2010) with Dr. K. Patel and at the Institute of Molecular Medicine, The University of Texas Health Science Centre at Houston (2010-2013) with Dr. V. Narkar.
He joined the University of Hull in 2013 as a lecturer in Physiology and he moved to the Hull York Medical School in 2015.
Antonios became a fellow of the Higher Education Academy (FHEA) in 2015 and senior fellow (SFHEA) in 2017.
Office: Room 101, Allam Building, University of Hull.
His research interest focuses on the study of skeletal muscle plasticity in response to differing patho/physiological stimuli (e.g. nutritional interventions, damage/injury and exercise). Skeletal muscle is a highly plastic tissue that adapts to a variety of environmental challenges by changing its metabolic, functional and contractile properties. Discovery of key molecules and novel pathways that regulate the maintenance and repair of muscle tissue has important therapeutic implications in several metabolic and muscle degenerative diseases. A major focus is placed on studying how nuclear hormone receptors regulate all aspects of mitochondrial metabolism and skeletal muscle fibre growth, maintenance and regeneration in the context of metabolic and degenerative disorders associated with skeletal myopathies. Targeting nuclear receptors in the skeletal muscle can be exploited in order to assimilate their role in muscle physiology, using (epi)genetic mouse models, in vivo, in vitro and ex vivo approaches.
- The Royal Society (2015)
- The European Union (FP7 calls; 2014 - 2018)
Regulation of muscle stem cells by ERRγ “MUSTEMERR”
Skeletal muscle stem cells called the satellite cells are localised within the myofibre basal lamina and are activated upon muscle injury, they then proliferate and differentiate to replace the damaged muscle. Satellite cells play a crucial role in maintaining skeletal muscle homeostasis and repair and are the key rate-limiting step for successful regeneration. Recent evidence has improved our understanding of the mechanisms underlying skeletal muscle metabolic reprogramming and its ability regenerate after damage. In particular, Estrogen Related Receptors (ERR α, β and γ) are a sub-family of orphan nuclear hormone receptors that have been identified as major regulators of cellular and mitochondrial metabolism. In 2012/13 the fellow reported that skeletal muscle-specific over-expression of ERRγ drives metabolic and angiogenic muscle reprogramming that was beneficial in both health and disease.
The MUSTEMERR project tests the hypothesis that targeting ERRγ in skeletal muscle will improve the myofibre regenerative capacity via satellite cell recruitment and growth factor secretion. ERRγ–driven metabolic and angiogenic myofibre remodelling will be protective to muscle subjected to stimuli that cause damage and are followed by regeneration. The project is focused on the following main objectives: (1) To establish the satellite cell proliferation and differentiation profiles in ERRγ transgenic muscles at baseline and in response to acute eccentric exercise. (2) To investigate the effect of ERRγ on satellite cell recruitment in response to muscle injury. (3) To determine the interplay between muscular revascularisation and reparative myogenesis by ERRγ. (4) To determine whether an AAV-mediated ERRγ delivery increases satellite cell recruitment and improves muscle integrity and function.
Phase I (2014-2016) progress report
In the past two years we have made great progress towards the completion of objectives (1) and (2) and some effort has taken place addressing objective (3). During the project the fellow has found that ERRγ transgenesis does not result in an increase in skeletal muscle satellite cells. To our surprise the satellite cell pool of this mouse model is significantly lower compared to wild type mice. When this mouse is crossed with the hyper-muscular myostatin null mouse -that is known to have a satellite cell deficit-, the satellite cell number is further reduced and a large number of fibres has a single satellite cell. Fibre cultures revealed lower cells per cluster and fewer clusters compared to control despite a proportional increase in satellite cell progeny. Remarkably, when challenged with injury, ERRγ overexpression in myostatin deficient mice leads to accelerated muscle regeneration highlighting the importance of microcirculation during regeneration.
Phase II (2016-2018) progress report
In the past two years we addressed objectives (3) and (4). During the second phase of the project the fellow generated strong evidence on the linking the growth factors that can be isolated from blood with skeletal myogenesis in vitro ex vivo and most importantly in vivo. Strikingly, we found that growth factors contained in the releasate from platelets promotes muscle stem cell commitment-to-differentiation and accelerate skeletal muscle regeneration in response to acute injury. These results provide important mechanistic evidence that can be exploited in regenerative medicine and have been published. Secondly, our work provided novel evidence that the dystrophin-associated glycoprotein complex is a highly adaptable structure that responds to the metabolic nature of the fibre. In addition, we used adeno-associated viral gene delivery to epigenetically induce ERRγ expression in the mouse. We found that administration of AAV8-ERRγ into the tibialis anterior muscle resulted in increased succinate dehydrogenase and lower central nucleation in muscles of dystrophic mice in an age-specific manner. These findings were independent of muscle stem cell proliferation and differentiation profiles.
Since the initiation of the grant, the fellow was appointed as a Lecturer in Biomedical Sciences at the Hull York Medical School, University of Hull and he was recently promoted to Senior Lecturer. He made substantial progress in his career goals by creating his own research group composed currently of 3 fully funded PhD students and his group is supported by 1 technician. In the meantime, one PhD and one MSc student have completed their studies successfully within the University defined timelines. He also co-supervises 2 PhD students from other laboratories. Since the start of the project he has published 10 articles, two of which contain findings of the MUSTEMERR project (i.e. Matsakas et al. Elife. 2016 Aug 5;5. pii: e16940 and Scully et al. Acta Physiol. 2018, e13207).
Dr Matsakas provides SSCs in Skeletal Myogenesis, Metabolic Homeostasis, Molecular Physiology and Skeletal Muscle Regeneration.Publications
For the full publications list, please click here.
- Omairi S, Matsakas A, Degens H, Kretz O, Hansson KA, Solbrå AV, Bruusgaard JC, Joch B, Sartori R, Giallourou N, Mitchell R, Collins-Hooper H, Foster K, Pasternack A, Ritvos O, Sandri M, Narkar V, Swann JR, Huber TB, Patel K. (2016). Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres. Elife. 5. pii: e16940. doi: 10.7554/eLife.16940. PMID: 27494364
- Matsakas A, Prosdocimo DA, Mitchell R, Collins-Hooper H, Giallourou N, Swann JR, Potter P, Epting T, Jain MK, Patel K. (2015). Investigating mechanisms underpinning the detrimental impact of a high fat diet in the developing and adult hypermuscular myostatin null mouse. Skelet Muscle. 5:38. eCollection, PMID:26644908
- Collins-Hooper H, Sartori R, Giallourou N, Matsakas A, Mitchell R, Makarenkova H, Flasskamp H, Macharia R, Ray S, Swann JR, Sandri M, Patel K. (2015). Symmorphosis through Dietary Regulation: A Combinatorial Role for Proteolysis, Autophagy and Protein Synthesis in Normalising Muscle Metabolism and Function of Hypertrophic Mice after Acute Starvation. PLoS One. 10(3):e0120524, PMID: 25807490
- Yadav V, Matsakas A, Lorca S, Narkar V. (2014). PGC1β activates anti-angiogenic program to repress neo-angiogenesis in muscle ischemia. Cell Rep. (Jul 23. pii: S2211-1247(14)00524-5. doi: 10.1016/j.celrep.2014.06.040. [Epub ahead of print]), PMID: 25066120
- Collins-Hooper H, Sartori R, Macharia R, Visanuvimol K, Foster K, Matsakas A, Flasskamp H, Ray S, Dash PR, Sandri M, Patel K. (2014). Propeptide-Mediated Inhibition of Myostatin Increases Muscle Mass Through Inhibiting Proteolytic Pathways in Aged Mice. J Gerontol A Biol Sci Med Sci. 69:1049-59. PMID: 24414825
Professors Ketan Patel and Keith Foster, University of Reading, UKProfessor Vihang Narkar, University of Texas, USADr Nadira Yuldasheva, University of Leeds, UKDr Hans Degens, Metropolitan University of Manchester, UKProfessor Marco Patruno, University of Padova, Italy
Highly motivated students holding a good honours degree in any biomedical discipline who wish to pursue their PhD studies in molecular physiology and metabolic medicine are encouraged to contact me.