Vascular Tetraspanin Group

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Group leader: Dr Michael G Tomlinson


Our aim is to understand the complex “forest” of cell surface proteins that orchestrate cellular function.  We study platelets, the first aid kit of the bloodstream, and the endothelial cells that line our blood vessels, because of their critical roles in health and disease processes leading to heart attack and stroke.

Our research group

Platelets and endothelial cells play essential roles in maintaining blood vessel integrity and in wound healing, but can also give rise to the initiation and progression of atherosclerosis, leading to heart attack and stroke.  These cells possess an array of receptors and adhesion molecules that regulate their function in health and disease.  The tetraspanins are a superfamily of transmembrane proteins that interact with and “organise” other cell surface proteins into membrane nanodomains.  Such partitioning of proteins into membrane nanodomains is critical for processes such as cell signaling and adhesion.  Indeed, the fundamental importance of tetraspanins is underlined by their expression throughout the animal, plant and fungal kingdoms.  By identifying novel tetraspanin-associated proteins on platelets and endothelial cells, and characterizing their regulation within tetraspanin microdomains, we aim to identify new drug targets for the prevention and treatment of cardiovascular disease.

Our studies are focussed on genetically modified platelets and primary endothelial cells, with additional use of cell line models.  The techniques that we employ include genomics and proteomics, molecular biology, functional assays for platelets and endothelial cells, and analyses of protein-protein interactions through advanced microscopy and biochemical methods.

Specialist techniques:

  • Generation and characterisation of CRISPR/Cas9 knockout cell lines
  • Biochemical analyses of protein-protein interactions for membrane proteins
  • Quantitative two-colour western blotting using the Odyssey Infrared Imager
  • Luciferase reporter assays as a readout for cell signalling pathways

Current Projects

  • The Tspan14/ADAM10 dyad: a major regulator of Notch signaling in atherosclerosis? (Birmingham-Maastricht PhD Studentship)
  • Identifying the tetraspanin/ADAM10 ‘molecular scissor’ for the platelet collagen and fibrin receptor GPVI (BHF PhD Studentship)
  • Investigating tetraspanin function using mouse models (MRC Harwell Genome Editing Mice for Medicine (GEMM) Award)
  • Targeting platelet adhesion receptors in thrombosis – TAPAS (European Joint Doctorates International Training Network)
  • Understanding the mechanism by which tetraspanins regulate the ‘molecular scissor’ ADAM10 (BBSRC Project Grant)
  • Regulation of the store-operated Ca2+ entry channel Orai1 by platelet tetraspanin Tspan18 (BHF Project Grant)
  • Molecular mechanisms underlying platelet activation by oxidised low density lipoproteins - dissecting the composition of the platelet CD36 signalosome (BHF Project Grant)

Recent Publications

Matthews AL, Koo CZ, Szyroka J, Harrison N, Kanhere A, Tomlinson MG (2018) Regulation of leukocytes by TspanC8 tetraspanins and the ‘molecular scissor’ ADAM10.  Front Immunol, 9:1451.

Tomlinson MG (2017) Eye-opening potential for tetraspanin Tspan12 as a therapeutic target for diseases of the retinal vasculature.  Circulation 136: 196-9.

Haining EJ, Matthews AL, Noy PJ, Romanska HM, Harris HJ, Pike J, Morowski M, Gavin RL, Yang J, Milhiet PE, Berditchevski F, Nieswandt B, Poulter NS, Watson SP, Tomlinson MG (2017) Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation.  Platelets, 28: 629-42.  Plenary Paper.

Reyat JS, Chimen M, Noy PJ, Szyroka J, Rainger GE*, Tomlinson MG* (2017) ADAM10-interacting tetraspanins Tspan5 and Tspan17 regulate VE-cadherin expression and promote T lymphocyte transmigration.  J Immunol 199: 666-76.

Noy PJ, Yang J, Reyat JS, Matthews AL, Charlton AE, Furmston J, Rogers DA, Rainger GE, Tomlinson MG (2016) TspanC8 tetraspanins and ADAM10 interact via their extracellular regions: evidence for distinct binding mechanisms for different TspanC8s.  J Biol Chem 291: 3145-57.

For full publication lists see:


Principal Investigators
Michael G Tomlinson - School of Biosciences, Cells and Molecules

Internal Collaborators:
Fedor Berditchevski
Alexander Brill
Debbie Cunningham
Tim Dafforn
Victoria Heath
Neena Kalia
Aditi Kanhere
Farhat Khanim
Tim Mitchell
Natalie Poulter
Ed Rainger
Steve Watson

Postdoctoral Researchers:
Neale Harrison

PhD Students:
Chek Ziu (Connie) Koo
Alexandra Matthews
Justyna Szyroka
Xueqing Wang

External Collaborators:
Marjo Donners (Maastricht, The Netherlands)
Angel Garcia (Santiago, Spain)
Elizabeth Gardiner (Canberra, Australia)
Stefan Lichtenthaler (Munich, Germany)
Khalid Naseem (Leeds, UK)
Bernhard Nieswandt (Würzburg, Germany)
Annemiek van Spriel (Nijmegen, The Netherlands)