People

Professor Martyn Mahaut Smith

Professor of Cellular Physiology

School/Department: Molecular Cell Biology, Department of

Email: mpms1@leicester.ac.uk

Profile

My research career in Physiology and Pharmacology started with a PhD on voltage-gated ion channels (1983-86) under the supervision of Dr Robert Meech at the University of Bristol. This was followed by Post-Doc positions in Toronto (lymphocyte ion channels with Dr Lyanne Schlichter) Cambridge (platelet ion channels with Drs Tim Rink and Stewart Sage) and San Diego (calcium and cyclic nucleotide signalling with Prof Roger Tsien). In 1992 I returned to Cambridge funded initially by a British Heart Foundation Lectureship to continue work on platelet ion channels and calcium signalling. During this time I became fascinated by megakaryocyte function. In 2007 I moved to a Chair in Cellular Physiology at the University of Leicester. My long-standing interest in using state of the art techniques to study biological systems led to an appointment as Academic Head of Core Biotechnology Services (2015-2018) alongside teaching and research activities. In addition as current Chair of the Disability Equality Action Group I advocate for improved support for disabled University staff.

Research

1. Mechanisms of platelet activation in thrombosis and haemostasis. My lab is particularly interested in the role of ion channels and calcium-dependent proteins in platelet function. For many experiments we use the megakaryocyte as a surrogate for studies of signalling in the tiny anuclear platelet. Funded by the British Heart Foundation

2. Development of platelet-producing megakaryocytes from stem cells. We are investigating the mechanisms by which platelets develop within their precursor cell the megakaryocyte with a focus on its complex plasma membrane invagination system. Known as the demarcation membrane system (DMS) it shares several properties with the transverse tubular system of cardiac myocytes and can be studied using patch clamp or styryl fluorescent indicators. Funded by the MRC BBSRC and British Heart Foundation

3. Evolving areas of interest. Other areas of research include heart failure role of ion channels in immunity modulation of G-protein coupled receptors by ions and the cell membrane potential. Funded by the van Geest Heart and Cardiovascular Diseases Research Fund British Heart Foundation

Publications

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Wright JR, Jones S, Parvathy S, Kaczmarek LK, Forsythe I, Farndale RW, Gibbins JM, Mahaut-Smith MP. (2021) The voltage-gated K+ channel Kv1.3 modulates platelet motility and α2β1 integrin-dependent adhesion to collagen. Platelets Aug 4:1-11. doi: 10.1080/09537104.2021.1942818.

Bye, A.P, Gibbins, J.M. & Mahaut-Smith, M.P. (2020). Ca2+ waves coordinate purinergic receptor-evoked integrin activation and polarisation. Science Signaling Vol. 13, Issue 615, eaav7354. F1000 research paper.

Mahaut-Smith, M.P., Evans, R.J. & Vial, C. (2019). Development of a P2X1-eYFP receptor knock-in mouse to track receptors in real time. Purinergic Signaling, 15(3):397-402 https://doi.org/10.1007/s11302-019-09666-1

Ilkan, Z., Watson, S., Watson, S.P. & Mahaut-Smith, M.P. (2018). P2X1 receptors amplify FcγRIIa-induced calcium increases and functional responses in human platelets. Thrombosis & Haemostasis. 118:369-380

Ilkan Z., Wright JR, Goodall A.H., Gibbins J.M., Jones C.I. & Mahaut-Smith M.P. (2017). Evidence for shear-mediated Ca2+ entry through mechanosensitive cation channels in human platelets and a megakaryocytic cell line. J.Biol.Chem. 292:9204-9217. 

Osman S., Taylor, K.A., Allcock, N., Rainbow, R.D. & Mahaut-Smith, M.P. (2016). Detachment of surface membrane invagination systems by cationic amphiphilic drugs. Scientific Reports 6:18536.

Jones, S., Evans, R.J. & Mahaut-Smith, M.P. (2014) Ca2+ influx through P2X1 receptors amplifies P2Y1 receptor-evoked Ca2+ signaling and ADP-evoked platelet aggregation. Molecular Pharmacology 86:243-51

Taylor, K.A., Wright, J.R., Vial, C., Evans, R.J. & Mahaut-Smith, M.P. (2014). Amplification of human platelet activation by surface pannexin-1 channels. Journal of Thrombosis & Haemostasis. 12:987-98.

Vaiyapuri, S., Jones, C.I., Sasikumar, P.. Moraes, L.A., Munger, S.J., Wright, J.R., Ali, M.S., Sage, T., Kaiser, W.J., Tucker, K.L., Stain, C.J., Bye, A.P., Jones, S., Oviedo-Orta, E., Simon, A.S., Mahaut-Smith, M.P., & Gibbins, J.M. (2012). Gap Junctions and Connexin Hemichannels Underpin Haemostasis and Thrombosis. Circulation 125, 2479-2491. 

Fung, C.Y.E, Jones, S., Ntrakwah, A., Naseem, K.M. Farndale, R.W. & Mahaut-Smith, M.P.  (2012). Platelet Ca2+ responses coupled to glycoprotein VI and Toll-like receptors persist in the presence of endothelial-derived inhibitors. Blood 119, 3613-3621.

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Supervision

Development of platelet-producing megakaryocytes from stem cells

Role of ion channels and calcium sensors in thrombosis thromboinflammation and haemostasis

The role of specialised membrane invagination systems in platelets megakaryocytes and cardiac myocytes

Regulation and function of the voltage-gated K+ channel Kv1.3 

Teaching

I teach on modules across all 3 years of the BSc degrees within the School of Biological Sciences. Topics include: Cardiovascular physiology Stem cell therapies Basic pharmacology Core principles of physiology Exercise physiology Therapeutic benefits of exercise.

Modules taught during 2021-22: BS3056: MB3057; MB3001; BS2014; BS2013 (Module convenor); BS1060. 

Press and media

Together with Prof. Jonathan Gibbins (University of Reading) I have edited four volumes of the popular Methods in Molecular Biology books published by Humana Press (now Springer). These four volumes contain more than 100 Chapters in which experts across the globe have shared their knowledge and expertise of a wide variety of standard and advanced techniques for the study of platelets and megakaryocytes.

http://www.springer.com/gb/book/9781617793066

http://www.springer.com/gp/book/9781588290113

http://www.springer.com/gb/book/9781588291011

https://www.springer.com/la/book/9781493985845 

Activities

Member of learned societies: Physiological Society British Pharmacological Society

British Biophysical Society Royal Microscopy Society

2009-present: Member Cardiovascular Biomedical Research Unit Glenfield Hospital Leicester

2010-present: Review Editorial Board of “Frontiers in Membrane Physiology and Biophysics”

2021-present: National Association of Disabled Staff Networks STEM Action group 

Awards

Invited talks:

Sept 2020 (postponed to 2022): Ion Channels. The Platelet Society Summer School:

2017: Calcium channels. European Platelet Summer School

2015: Keynote Lecture: Channels and pores in the platelet and megakaryocyte membrane. UK Platelet Meeting

2015: Dynamics of platelet and megakaryocyte membranes. Gordon Conference on Cell Biology of Platelets and Megakaryocytes)

2014. Voltage control of G-protein-coupled receptors. Frontiers in Synaptic Function Jerusalem 11-14 Jan 2014.

Qualifications

BSc Physiology University of Sheffield

PhD Physiology University of Bristol

MA University of Cambridge

Senior Fellow Higher Education Academy 

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