Tom Carter graduated from King's College London in 1986 with a joint honors degree in Physiology and Pharmacology and then carried out research for a PhD in Pharmacology in the group of Professor Jeremy Pearson in the Vascular Biology Unit of the MRC Clinical Research Center in Harrow, London.
His PhD work established a crucial role for intracellular calcium as the major trigger for the synthesis of prostacyclin (a potent vasodilator and anti-platelet mediator) during purinoceptor-activation in human endothelial cells. In 1989 he moved to the laboratory of Dr David Ogden in the Division of Neurophysiology at the MRC National Institute for Medical Research (NIMR) to learn and apply whole cell patch clamp, fluorescence photometry and flash photolysis techniques. Here he studied the mechanisms that underlie the generation of hormone-evoked calcium signals in endothelial cells and established the use of novel caged nitric oxide donors for the quantitative investigation of nitric oxide action in vascular tissues.
In 1995 he was awarded a British Heart Foundation Gerry Turner Fellowship and in 1998 a British Heart Foundation Basic University Lectureship. In 1998 he moved from the NIMR to join the Pharmacology Department at University College London as a lecturer and an honorary lecturer in Clinical Pharmacology. In 2003, he returned to NIMR, to take up a Career Scientist position within the Division of Molecular Neuroendocrinology where he concentrated on developing and applying new tools for high resolution, high speed, multicolour imaging of the intracellular trafficking and exocytosis of individual secretory granules in living endothelial cells.
In 2009 he became Acting Head of the Division of Molecular Neuroendocrinology and in 2010 became a Principle Investigator in the Division of Physical Biochemistry at NIMR. In October 2013 he joined the Division of Biomedical Sciences at St George's University of London as Professor of Endothelial Cell Biology. In 2016 he became head of the Cell Biology & Genetics research center at St George's University, and was elected a Fellow of the Royal Society of Biology (FRSB).
Professor Tom Carter’s research is aimed at identifying the molecular mechanisms that control the regulated secretion of coagulant and inflammatory mediators from vascular endothelial cells.
Endothelial cells line the lumen of all blood vessels and together constitute one of the largest and most complex secretory organs in the body. Endothelial cells control vital physiological processes such as blood flow, blood clotting, inflammation, vessel growth and wound healing through the secretion of a variety of coagulant, inflammatory and angiogenic molecules. Endothelial cell dysfunction alters the balance of secreted molecules and increases the risk of hypertension, ischemia, stroke, heart attack, infection and cancer. The mechanisms controlling the synthesis, packaging, trafficking and secretion of molecules in endothelial cells represent targets for modifying endothelial cell function in health and disease. Professor Carter’s group’s goal is to understand how endothelial cells secrete mediators directly implicated in human health and disease under “normal” and “perturbed” conditions. A better understanding of the basic cellular processes by which endothelial cells function will translate into novel therapeutic agents for human medicine.
Professor Carter’s current work focuses on the biology of Weibel-Palade bodies (WPBs), the main regulated secretory granule of endothelial cells. WPBs contain von Willebrand factor, a pro-coagulant and adhesive molecule that plays a vital role in haemostasis.
Professor Carter’s current work comprises three interrelated strands of research which address the following questions:
- How is the transport, exocytosis and recycling of WPBs in endothelial cells controlled and regulated?
- What are the structural changes in von Willebrand Factor and WPBs during granule maturation, export and secretion?
- How is WPB fusion pore opening and closing regulated and controlled?
P-selectin mobility undergoes a sol-gel transition as it diffuses from exocytosis sites into the cell membrane. Hellen N, Mashanov GI, Conte IL, le Trionnaire S, Babich V, Knipe L, Mohammed A, Ogmen K, Martin-Almedina S, Török K, Hannah MJ, Molloy JE, Carter T. Nat Commun. (2022).13(1):3031. doi: 10.1038/s41467-022-30669-x. PMID: 35641503
GDP/GTP exchange factor MADD drives activation and recruitment of secretory Rab GTPases to Weibel-Palade bodies. Marije Kat, Petra E. Bürgisser, Hans Janssen, Iris M. De Cuyper, Ianina Conte, Alistair N. Hume, Tom Carter, Jan Voorberg, Coert Margadant and Ruben Bierings (2021). Blood Advances 5(23):5116-5127.doi: 10.1182/bloodadvances.2021004827. PMID:34551092
Stimulated release of intraluminal vesicles from Weibel-Palade bodies. Streetley J, Fonseca AV, Turner J, Kiskin NI, Knipe L, Rosenthal PB, Carter T.(2019). Blood. 133(25):2707-2717.doi: 10.1182/blood-2018-09-874552. Epub 2019 Feb 13. PMID: 30760452
WPBs: making a mark and leaving a trail. Carter T, Bierings R. (2019) Blood;134(12):909-910. doi: 10.1182/blood.2019002322. PMID: 31537537PMID: 34551092 Free PMC article.
Synaptotagmin 5 regulates calcium-dependent Weibel-Palade body exocytosis in human endothelial cells. Camille Lenzi, Jennifer Stevens, Daniel Osborn, Matthew J. Hannah, Ruben Bierings, and Tom Carter. J cell Sci (2019). PMID: 30659119
Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells. Schillemans M, Karampini E, van den Eshof BL, Gangaev A, Hofman M, van Breevoort D, Meems H, Janssen H, Mulder AA, Jost CR, Escher JC, Adam R, Carter T, Koster AJ, van den Biggelaar M, Voorberg J, Bierings R. (2018). Arterioscler Thromb Vasc Biol. 38(7):1549-1561. PMID: 29880488.
Interaction between MyRIP and the actin cytoskeleton regulates Weibel-Palade body trafficking and exocytosis. Conte IL, Hellen N, Bierings R, Mashanov GI, Manneville JB, Kiskin NI, Hannah MJ, Molloy JE, Carter T.(2016). J Cell Sci. 129(3):592-603.PMID: 26675235
Is there more than one way to unpack a Weibel-Palalde body? Conte IL, Cookson EA, Hellen N, Bierings R, Mashanov, G, Carter T. (2015). Blood 126(18):2165-7. DOI 10.1182/blood-2015-08-664961. PMID: 26377598
STXBP1 promotes Weibel-Palade body exocytosis through its interaction with the Rab27A effector Slp4-a. Dorothee van Breevoort et al. (2014). Blood. 123(20):3185-94. PMID 24700782
The interplay between the Rab27A effectors Slp4 a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis. Bierings R, Hellen N, Kiskin N, Knipe L, Fonseca AV, Patel B, Meli A, Rose M, Hannah MJ, Carter T. (2012). Blood. 120: 2757-2767. PMID 22898601
Structural organization of Weibel-Palade bodies revealed by cryo-EM of vitrified endothelial cells. Berriman JA, Li S, Hewlett LJ, Wasilewski S, Kiskin FN, Carter T, Hannah MJ, Rosenthal PB (2009). Proc Natl Acad Sci U S A, 106, 17407-17412. PMID 19805028
Selective release of molecules from Weibel Palade bodies during a lingering kiss. Babich V, Meli A, Knipe L, Dempster JE, Skehel P, Hannah MJ, Carter T. (2008). Blood, 111:5282-5290. PMID 18252862 (Plenary paper).
Dr Katalin Török (Cell Biology Research Centre, SGUL).
Dr Daniel Osborne (Genetics Research Centre, MCS SGUL).
Dr Soo-Hyun Kim (Cell Biology & Genetics Research Centre, SGUL)
Dr Suman Rice (IMBE, SGUL).
Dr Justin Molloy, (Crick Institute Mill Hill Laboratory, London). Molecular motors and single molecule imaging. https://www.crick.ac.uk/research/a-z-researchers/researchers-k-o/justin-molloy/
Dr Peter Rosenthal, (Crick Institute Mill Hill Laboratory, London). Structural studies of endothelial cells and their secretory granules; https://www.crick.ac.uk/research/a-z-researchers/researchers-p-s/peter-rosenthal/
Dr David Ogden (Universite Paris Descartes, Paris). Flash photolysis and exocytosis; http://www.biomedicale.parisdescartes.fr/physiocer/?page_id=3044
Dr Paul Skehel (Center for Intergrative Physiology, University of Edinburgh). P-selectin trafficking and secretion; http://www.ed.ac.uk/integrative-physiology/staff-profiles/research-groups/paul-skehel
Dr John Dempster (University of Strathclyde). Development of imaging and electrophysiology software and instrumentation; http://www.strath.ac.uk/staff/dempsterjohndr/
Professor Caroline Wheeler-Jones (Royal Veterinary College, London). Prostaglandin synthesis and release; http://www.rvc.ac.uk/about/our-people/caroline-wheeler-jones
Dr Matthew Hannah Dr Matthew Hannah (Microbiology Services Division Colindale, Public Health England, London). EM and cell biology of secretory pathway. https://www.researchgate.net/profile/Matthew_Hannah
Dr Ruben Bierings, (Department of Hematology, Cancer Institute, Erasmus MC, Rotterdam, Netherlands). Trafficking and secretions in the vasculature. https://www.erasmusmc.nl/en/cancer-institute/research/groups/hematology-bierings-lab
Dr Jean-Baptiste Manneville. (Institute Curie, Subcellular Structure & Cellular Dynamics). Mechanisms of Weibel-Palade body trafficking and exocytosis. http://umr144.curie.fr/en/profile/jean-baptiste-manneville-001243