The main aim of my lab is to investigate the role of the actin cytoskeleton in both platelet and megakaryocyte cell function. This involves the use of flourescent, confocal and super resolution microscopy within both platelet spreading and thrombus formation assays. The main projects within the lab at present are:
Project 1: The role of cyclic nucleotides in the control of platelet reversal
This project is a non-clinical PhD studentship funded by the British Heart Foundation designed to understand how the cyclic nucleotides, prostacyclin and nitric oxide, can not only prevent platelet activation, but can also drive its reversal predominately by understanding the effects on the actin cytoskeleton. This ability to reverse platelet activation is key to restricting the size of a thrombus, and therefore preventing the formation of occlusive thrombi, which can lead to heart attacks or strokes.
Funding: British Heart Foundation
Project 2: Thrombiglow: 'Smart' Multimodal Platelet specific 'Theranostic' Drug Delivery Imaging Agents
This project is a British Heart Foundation non-clinical PhD studentship that is in collaboration with Dr Graeme Stasiuk (PI). Anti-platelet therapy at present uses drugs that are non-specific and have side-effects on bleeding, and in the case of Aspirin, stomach ulceration. This proof of concept project will design a drug therapy using nanoparticles that would target platelets specifically, reduce side-effects such as bleeding, whilst maximising platelet inhibition, and so help to prevent thrombus formation.
Funding: British Heart Foundation
Project 3: How is platelet/megakaryocyte activation affected by oxLDL?
This project is a PhD studentship that is designed to understand how oxLDL in combination with other matrix proteins can modulate platelet and megakaryocyte activation in different conditions. OxLDL is a component of the blood that has been shown to induce inflammation and a prothrombotic phenotype within the vasculature. It can combine with other matrix proteins, and potentiate the formation of thrombi, leading to an increased chance of forming an occlusive thrombus. We are investigating the mechanism behind this potentiation by understanding how the actin cytoskeleton responds to these combinations of matrix proteins.
Funding: The University of Hull
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.
1) BHF PhD studentship “Platelet cAMP signaling controls thrombosis through enhanced embolisation” 2015-2018 (£106,468)
2) BHF PhD studentship (Co-PI) "ThrombiGlow: ‘Smart’ Multimodal Platelet Specific ‘Theranostic’ Drug Delivery Imaging Agents (107,147) 2017-2020 (with Dr Graeme Stasiuk (PI))
Present Lab Members
Lloyd Atkinson (PhD): BHF student 2015-2018
Yusra Ahmed (PhD): University of Hull Studentship 2016-2019
Michelle Kinnon (PhD): BHF student 2017-2020 (PI Graeme Stasiuk)
Past lab Members
Muhammad Yusuf: PhD awarded 2017
I am responsible for 3 blocks within the Phase 1 (Year and 2) curriculum within the Hull York Medical School. The Year 1 block is You are What you Eat, a Year 1 MBBS block which covers digestion, and the metabolism of carbohydrate, protein and lipids
In addition I am block lead for Year 2 block Kidney form and function, and Gastrointestinal pathophysiology, which cover the physiology, and function of the kidney, and diseases of the GI tract respectively.
In addition to this I am involved in teaching pharmacology to Year 1 and Year 2 MBBS students.
I also have a number of undergraduate and masters lab projects each year.
1) MZ Yusuf, Z Raslan, L Atkinson, A Aburima, SG Thomas, KM Naseem, and SDJ Calaminus. Prostacylin reverses platelet spreading leading to instability of thrombus formation via cAMP mediated regulation of RhoA activity. Scientific Reports 2017
2) Sinclair A, Park L, Shah M, Drotar M, Calaminus S, Hopcroft L.E.M, Kinstrie R, Guitart A.V, Dunn K, Abraham S.A, Sansom O, Michie A.M, Machesky L, Kranc K.R, Graham G.J, Pellicano F, Holyoake T.L. cxcr2 and CXCR4 regulate survival and self-renewal of haematopoietic stem/progenitor cells. Blood, 2016. http://dx.doi.org/10.1182/blood-2015-08-661785
3) Schachtner H., Calaminus S.D.J., Thomas S.G., Machesky L.M. Podosomes in adhesion, migration, mechanosensing and matrix remodelling. Cytoskeleton, 2013.
4) Schachtner H., Calaminus S.D.J., Sinclair A., Moneypenny J., Blundell M., Thrasher A.J., Michie A., Vukovic M., Jones G.E., Thomas S.G., Watson S.P., Machesky L.M. Megakaryocytes assemble podosomes that degrade matrix and protrude through basement membrane. Blood, 2013.
5) †Calaminus S.D.J., †Guitart A., †Sinclair A., Schachtner H., Watson S.P., Holyoake T.L., Kranc K.R., Machesky L.M. Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny. Plos One, 2012. (†Joint first authors)
6) Zech T., Calaminus S.D.J., Machesky L.M. Actin on Traffic. How actin controls receptor transport. Point of view article. Cell adhesion and Migration, 2012.
7) Schachtner H., Li A., Stevenson D., Calaminus S.D.J., Thomas S.G., Watson S.P., Sixt M., Wedlich-Soldner R., Strathdee D., Machesky L.M. Tissue inducible lifeact expression visualizes actin dynamics in vitro and in vivo. Experimental Cell Research 2012.
8) Zech T†., Calaminus S.D.J†., Caswell P., Spence H.J., Carnell M., Insall R.H., Norman J., Machesky L.M. The Arp2/3 activator WASH regulates a5b1 integrin mediated invasive migration. Journal of Cell Science Nov: 2011. (†Joint first authors)
9) Thomas S.G., Calaminus S.D.J., Machesky L.M., Alberts A.S., Watson S.P. G-protein coupled and ITAM receptor regulation of the formin FHOD1 through Rho Kinase in platelets. Journal of Thrombosis and Haemostasis. 2011 Aug;9(8):1648-51
10) Carnell M., Zech T., Calaminus S.D.J., Ura S., Hagedorn M., Johnston S., May R., Soldati T., Machesky L.M., Insall R.H. WASH-Dependent Actin Polymerization Causes Vesicle Neutralization and Exocytosis by Driving Removal of V-ATPase. Journal of Cell Biology 2011.
11) Calaminus S.D.J., Thomas S., McCarty O.J., Machesky L.M., Watson S.P. Identification of a novel actin rich structure, the actin nodule, in the early stages of platelet spreading. Journal of Thrombosis Haemostasis. 2008.
12) Thomas S.G., Calaminus S.D.J., Auger J.M., Watson S.P., Machesky L.M. Studies on the actin-binding protein HS1 in platelets. BMC Cell Biology. 2007.
13) Tomlinson M.G., Calaminus S.D.J., Berlanga O., Auger J.M., Bori-Sanz T., Meyaard L., Watson S.P. Collagen promotes sustained glycoprotein VI signalling in platelets and cell lines. Journal of Thrombosis and Haemostasis. 2007.
14) * Calaminus S.D.J., Auger J.M., McCarty O.J.T., Wakelam M.J.O., Machesky L.M., Watson S.P. Myosin II is required for platelet structure during spreading, and is required for thrombus stability. Journal of Thrombosis and Haemostasis. 2007.
15) Calaminus S.D.J., McCarty O.J.T., Auger J.M., Insall R.H., Watson S.P., Machesky L.M. A major role for Scar/WAVE-1 downstream of GPVI in platelets. Journal of Thrombosis and Haemostasis. 2007.
16) Pearce A.C., McCarty O.M.J., Calaminus S.D.J., Turner M., Vigorito E., Watson S.P. Vav family proteins are required for optimal regulation of PLCgamma2 by integrin alphaIIbbeta3. Biochemical Journal. 2007.
17) McCarty O.J.T., Calaminus S.D.J., Berndt M.C., Machesky L.M., Watson S.P. Von Willebrand factor mediates platelt spreading through glygoprotein ib and aiibb3 in the presence of botrocetin and ristocetin, respectively. Journal of Thrombosis and Haemostasis. 2006.
18) Pettitt T.R., Dove S.K., Lubben A., Calaminus S.D.J., Wakelam M.J.O. Analysis of intact phosphoinositides in biological samples. Journal of Lipid Research 2006.
* Awarded 2007 Journal of Thrombosis and Haemostasis young scientist paper of the year