School of Sport, Exercise and Health Sciences

Staff

Professor Mark Lewis

Photo of Professor Mark Lewis

Dean of School and Professor of Musculoskeletal Biology

Musculo-Skeletal Biology Research Group

Professor Mark Lewis talks about his research

Muscle cellular and molecular physiology

Biomedicine of sport and exercise

Expertise is the design and development of in vitro systems that are as much “like” the actual tissue as possible. The approaches that have been taken are those common in regenerative medicine such as cell transplantation and tissue engineering. The major area here is the musculoskeletal system esp. skeletal muscle although I have also published in ligament/tendon and bone.

In the skeletal muscle systems (muscle cellular and molecular physiology), the ability to stimulate the tissue engineered constructs either electrically or mechanically is critical. The ability to do this of course then lends itself well to studies of exercise physiology. There is a portfolio of work in this area currently studying hypertrophy, training regimes, effects of steroids, aging, responses to hypoxia, species and anatomical differences, muscle derived stem cells and interactions with the nervous system.

There is significant overlap with the work above and that in sports medicine. The musculoskeletal work is one part of that however I also work in the wider area of what I term biomedicine of sport. I have a programme of work that looks at how tissue damaged during physical activity can be effectively repaired. This includes skin and related tissues and bone. Again, tissue engineered constructs are widely used whilst application tends to be focussed on cell therapy. In this regards, I have acted as scientific consultant to three different biotechnology companies providing expert opinion on biological and technical questions relating to various regenerative medicine processes and products.

Current Research Projects and Sources of Funding

Muscle cellular and molecular physiology
  • Engineering fully functional, integrated skeletal muscle
    Samantha Passey (PDRA)
    NC3Rs Project Grant
  • The HEAL Research Programme: Health, Epigenetics, Ageing and Learning
    Amarjit Saini (PDRA)
    HEFCE funded
  • Mimicking in-vivo skeletal muscle ageing in-vitro using three dimensional bioengineered constructs
    Adam Sharples (PDRA)
    HEFCE funded
  • Development of a Microfluidic Chamber for the In Vitro Study of Skeletal Muscle Innervation
    TBC (PDRA)
    Dr Hadwen Trust for Humane Research Project Grant
  • Peripheral vascular adaptations to low load resistance exercise with blood flow restriction
    Julie Hunt (PhD)
    HEFCE funded
  • Peripheral vascular adaptations to resistance exercise interventions; cellular & molecular
    mechanisms
    Emilia Thompson (PhD)
    HEFCE funded
  • The development of a skeletal muscle model of insulin resistance: Validation from two-dimensional to three-dimensional cultures
    Mark Turner (PhD)
    Self-funded
  • Direct effect of oxygen saturation on skeletal muscle function
    Carla Gallagher (PhD)
    HEFCE funded
  • Molecular mechanisms of action of anabolic steroids
    David Hughes (PhD)
    HEFCE funded
  • Development of 3D culture systems for fish muscle cells to investigate environmental adaptability 
    Krishan Vishnolia (PhD)
    Overseas industry funded
  • Molecular mechanisms underlying deterioration of muscular performance with age
    Paul Davies (PhD)
    HEFCE funded
  • Response of the Heat shock protein system to manipulation by external physiological factors
    James Tuttle (PhD)
    HEFCE funded
  • An In Vitro Model for Skeletal Muscle Adaptation Following Exercise Related Physiological Cues
    Darren Player (PhD)
    HEFCE funded
  • Cellular and molecular determinants of skeletal muscle hypertrophic potential
    Neil Martin (PhD)
    HEFCE funded
Biomedicine of sport and exercise
  • In-Vitro 3D bone tissue modelling: insights into Ameloblastoma pathogenesis
  • Claire Raison (PhD)
  • Driving oral mucosal epithelial cells towards a corneal phenotype for therapeutic transplantation
  • Anna O’Callaghan (PDRA)
  • Fight for Sight (Project Grant)
  • NHS National Institute of Health Research
  • Invention for Innovation (i4i) Early Stage Research Award

Completed Research Projects and Sources of Funding

Muscle cellular and molecular physiology
  • Motoneuron innervation of 3D skeletal muscle organoids
    Alec Smith (PhD)
    MRC Studentship
    PhD awarded 2012
  • Optimising training programmes for developing, strength, power and speed
    Iain Fletcher (PhD)
    PhD awarded 2011
  • Comparative molecular and physical analysis of bone produced from muscle and bone marrow derived adult stem cells
    EPSRC Studentship
    Karin Karlqvist (PhD)
    PhD awarded 2010
  • Soluble glass fibres as a scaffold for regenerating masseter muscle
    Rishma Shah (PhD)
    PhD awarded 2010
  • Masseter muscle gene expression in relation to various craniofacial deformities: A genotype
    phenotype study
    British Orthodontic Society Foundation Award
    Hadwa Moawad (PhD)
    PhD awarded 2009
  • The effects of diabetes mellitus on bone regeneration potential on the temporal sequence of healing events following guided bone regeneration
    Maria Retzepi (PhD)
    PhD awarded 2009
  • From Muscle to Tendon: Muscle Derived Stem Cells for the engineering of new fascia
    UCLH CRDC Project Grant
    2006 to 2008
  • Tissue engineering of human neo-muscle organoid using mechanical stimulation
    Royal National Orthopaedic Hospital PhD Studentship
    Mariea Brady (PhD)
    PhD awarded 2008
  • Gene therapy applications for muscle repair & muscular dystrophy using IGF-1 isoforms
    MRC Studentship
    Kenan Ates (PhD)
    PhD awarded 2007
Biomedicine of sport and exercise
  • The use of dielectrophoresis in oral cancer
    Hayley Mulhall (PhD)
    PhD awarded 2011
  • Dielectrophoresis as a prognostic tool for potentially malignant and malignant disease of the mouth 
    National Institute of Health Research (Research for Innovation, Speculation and Creativity)
    2007 to 2008
  • Phenotypic differences between the ability of oral and dermal fibroblasts to repair dermal lesions
    Batool Kazmi (PhD)
    PhD awarded 2009
  • Phenotypic differences between the ability of oral and dermal fibroblasts to repair dermal lesions 
    UCLH CBRC  (New Initiative Funding)
    Industrial PhD Studentship (Isolagen Europe Ltd.)
    2005 to 2008
  • Visiting Professor, Institute of Sport and Physical Activity Research (ISPAR) Bedford, University of Bedfordshire.
  • Visiting Professor, School of Life and Medical Sciences, University College London.
  • Visiting Professor, Cranfield Health, Cranfield University.
  • Executive Editor (2010 to current), Biotechnology Letters.
  • Reviewer for 28 journals.
  • Elected member of the Tissue and Cell Engineering Society Management Committee (Treasurer, 2008 to date).
  • Elected member of the EPSRC Peer Review College.
  • Grant Review for BBSRC, EPSRC, MRC, SFI (Science Foundation, Ireland), EFFORT, NC3Rs, British Lung Foundation, Action Medical Research, European Orthodontic Society, Scottish Executive Health Department and The Wellcome Trust.
  • External examiner for the MSc Exercise Physiology, University of Chichester (2010 to 2014).

Selected Invited Conference Keynote and Speaker Presentations

  • Tissue and Cell Engineering Society (TCES), Leeds University, UK (2011) From Jaws to Jumpers: Bioengineered skeletal muscle and its applications from surgery to exercise physiology – Keynote Presentation.
  • British Association of Sport and Exercise Sciences (BASES) ExPhys 2.0: New ways of looking at fatigue in vitro – keynote at BASES 2011 (Essex) symposium “Molecular cell biological approaches to fatigue”
  • Leeds Metropolitan University, Carnegie Seminar Series, UK (2011) – ExPhys 2.0: biotechnology "meats" exercise science.
  • The School of Clinical Dentistry, Seminar Series, The University of Sheffield, UK (2010) – From Jaws to Jumpers: bioengineered skeletal muscle and its applications from surgery to exercise physiology.

Muscle cellular and molecular physiology

  • ATES, K., YANG, S. Y., ORRELL, R. W., SINANAN, A. C. M., SIMONS, P., SOLOMON, A., BEECH, S., GOLDSPINK, G. & LEWIS, M. P. 2007. The IGF-I splice variant MGF increases progenitor cells in ALS, dystrophic, and normal muscle. Febs Letters, 581, 2727-2732.
  • BRADY, M. A., LEWIS, M. P. & MUDERA, V. 2008. Synergy between myogenic and non-myogenic cells in a 3D tissue-engineered craniofacial skeletal muscle construct. Journal of Tissue Engineering and Regenerative Medicine, 2, 408-417.
  • CARLQVIST, K. H., LEWIS, M. P., HUNT, N. P. & SHAH, R. 2010. Regeneration of Jaw Muscle—Potential Cellular Mechanisms. Seminars in Orthodontics, 16, 147-152.
  • HARZER, W., MARICIC, N., GEDRANGE, T., LEWIS, M. P. & HUNT, N. P. 2010. Molecular Diagnosis in Orthodontics, Facial Orthopedics, and Orthognathic Surgery: Implications for Treatment Progress and Relapse. Seminars in Orthodontics, 16, 118-127.
  • MOAWAD, H. A., SINANAN, A. C., LEWIS, M. P. & HUNT, N. P. 2011. Grouping patients for masseter muscle genotype-phenotype studies. Angle Orthod.
  • MUDERA, V., SMITH, A. S. T., BRADY, M. A. & LEWIS, M. P. 2010. The Effect of Cell Density on the Maturation and Contractile Ability of Muscle Derived Cells in a 3D Tissue-Engineered Skeletal Muscle Model and Determination of the Cellular and Mechanical Stimuli Required for the Synthesis of a Postural Phenotype. Journal of Cellular Physiology, 225, 646-653.
  • MULHALL, H., PATEL, M., ALQAHTANI, K., MASON, C., LEWIS, M. P. & WALL, I. 2011a. Effect of capillary shear stress on recovery and osteogenic differentiation of muscle-derived precursor cell populations. Journal of Tissue Engineering and Regenerative Medicine, 5, 629-635.
  • PASSEY, S., MARTIN, N., PLAYER, D. & LEWIS, M. P. 2011. Stretching skeletal muscle in vitro: does it replicate in vivo physiology? Biotechnol Lett, 33, 1513-21.
  • PATEL, M., MULHALL, H., AL-QUATANI, K., LEWIS, M. & WALL, I. 2011. Muscle-derived precursor cells isolated on the basis of differential adhesion properties respond differently to capillary flow. Biotechnology Letters, 33, 1481-1486.
  • SCULTHORPE, N., SOLOMON, A. M., SINANAN, A. C. M., BOULOUX, P. M. G., GRACE, F. & LEWIS, M. P. 2011. Androgens affect myogenesis in vitro and increase local IGF-1 expression. Medicine & Science in Sports & Exercise.
  • SHAH, R. & LEWIS, M. P. 2010. The Future? Craniofacial Skeletal Muscle Engineering as an Aid for the Management of Craniofacial Deformities. Seminars in Orthodontics, 16, 153-162.
  • SHARPLES, A. P., AL-SHANTI, N., LEWIS, M. P. & STEWART, C. E. 2011. Reduction of myoblast differentiation following multiple population doublings in mouse C2 C12 cells: a model to investigate ageing? Journal of cellular biochemistry, 112, 3773-85.
  • SINANAN, A. C. M., MACHELL, J. R. A., WYNNE-HUGHES, G. T., HUNT, N. P. & LEWIS, M. R. 2008. alpha v beta 3 and alpha v beta 5 integrins and their role in muscle precursor cell adhesion. Biology of the Cell, 100, 465-477.
  • SMITH, A. S., PASSEY, S., GREENSMITH, L., MUDERA, V. & LEWIS, M. P. 2011. Characterisation and optimisation of a simple, repeatable system for the long term in vitro culture of aligned myotubes in 3D. J Cell Biochem.
  • SMITH, A. S. T., SHAH, R., HUNT, N. P. & LEWIS, M. P. 2010. The Role of Connective Tissue and Extracellular Matrix Signaling in Controlling Muscle Development, Function, and Response to Mechanical Forces. Seminars in Orthodontics, 16, 135-142.

Biomedicine of sport and exercise

  • BHADAL, N., WALL, I. B., PORTER, S. R., BROAD, S., LINDAHL, G. E., WHAWELL, S. & LEWIS, M. P. 2008. The effect of mechanical strain on protease production by keratinocytes. British Journal of Dermatology, 158, 396-398.
  • BITAR, M., SALIH, V., KNOWLES, J. C. & LEWIS, M. P. 2008. Iron-phosphate glass fiber scaffolds for the hard-soft interface regeneration: The effect of fiber diameter and flow culture condition on cell survival and differentiation. Journal of Biomedical Materials Research Part A, 87A, 1017-1026.
    KAZMI, B., INGLEFIELD, C. J. & LEWIS, M. P. 2009. Autologous Cell Therapy: Current Treatments and Future Prospects. Wounds-a Compendium of Clinical Research and Practice, 21, 234-242.
  • KURTULUS, I., KAZMI, B., LEWIS, M. P., SOLAKOGLU, S., SCHUSTER, V., SCULLY, C., GOKBUGET, A. & WAHL, G. 2011. Altered functional activity patterns of fibroblasts related to periodontitis by systemic plasminogen deficiency (ligneous periodontitis). Quintessence International, 42, 601-609.
  • MOUTASIM, K. A., JENEI, V., SAPIENZA, K., MARSH, D., WEINREB, P. H., VIOLETTE, S. M., LEWIS, M. P., MARSHALL, J. F., FORTUNE, F., TILAKARATNE, W. M., HART, I. R. & THOMAS, G. J. 2011. Betel-derived alkaloid up-regulates keratinocyte alphavbeta6 integrin expression and promotes oral submucous fibrosis. Journal of Pathology, 223, 366-377.
  • MULHALL, H. J., LABEED, F. H., KAZMI, B., COSTEA, D. E., HUGHES, M. P. & LEWIS, M. P. 2011b. Cancer, pre-cancer and normal oral cells distinguished by dielectrophoresis. Analytical and Bioanalytical Chemistry, 401, 2455-2463.
  • RETZEPI, M., LEWIS, M. P. & DONOS, N. 2010. Effect of diabetes and metabolic control on de novo bone formation following guided bone regeneration. Clinical Oral Implants Research, 21, 71-79.
  • WALL, I. B., BHADAL, N., BROAD, S., WHAWELL, S. A., MUDERA, V. & LEWIS, M. P. 2009. Force generation and protease gene expression in organotypic co-cultures of fibroblasts and keratinocytes. Journal of Tissue Engineering and Regenerative Medicine, 3, 647-650.

Book Chapters

  • Hughes, D., Sculthorpe, N., Lewis, M.P. (2011). Molecular Aspects of Testosterone. in Grace, F. (ed.) Steroids. In preparation.
  • Lewis, M.P. (2011). Masticatory Muscles: Structure and Function. in McLoon, L., Andrade, F., (ed.) Craniofacial Muscles: A New Framework for Understanding the Effector Side of Craniofacial Muscle Control. Springer. In preparation.
  • Lewis, M.P. (2011). Fundamentals of cell and matrix biology. in Salih, V. (ed.) Standardisation in Cell and Tissue Engineering: Methods and protocols. Woodhead Publishing Limited. In preparation.
  • Lewis,M.P., Mudera,V., Cheema,U, Shah,R. (2009). Muscle Tissue Engineering. in Meyer,U., Meyer, Th., Handschel,J., Wiesmann,H.P., (ed.) Fundamentals of Tissue Engineering and Regenerative Medicine. Heidelberg: Springer. pp. 243-254.
  • Mudera,V., Cheema,U., Shah,R., Lewis,M. (2008). Improving biomaterials in tendon and muscle regeneration. in Di Silvio,L. (ed.) Cellular Response to Biomaterials. Cambridge: Woodhead Publishing Limited. ISBN: 1 84569 358 2.