I am a principal investigator in the Hull York Medical School, whose lab is investigating how platelets and megakaryocytes function. I am also the Programme Director for the MSc in Pharmacology and Drug Development.
Simon Calaminus obtained his PhD from the University of Birmingham in 2007 in which, he discovered the actin structure the actin nodule in platelet spreading, and also investigated the roles of Myosin II, Rho Kinase and Scar1 in platelet spreading and thrombus formation. He then completed post-doctoral studies in the laboratory of Professor Laura Machesky, at the Beatson Institute for Cancer Research, where he investigated the role of Wnt signaling and the podosome in megakaryocytes, alongside studies investigating the role of the WASP family member, WASH in cancer cell migration and integrin trafficking. In 2012 he was appointed as a lecturer at Hull York Medical School in 2012 and became a senior lecturer in 2019.
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 fluorescent, confocal and super resolution microscopy within both platelet spreading and thrombus formation assays. The main projects within the lab at present are:
Project 1: How is platelet inhibitory signaling altered by the vascular environment?
The vascular environment alters constantly throughout life. As the vascular environment changes it can then allow the formation of multiple different conditions, from diabetes, to dementia, and can also underlie vascular events such as stroke and heart attacks. A key cell within the blood, is the platelet.This cell is normally held in an inhibited state. However, as the vascular environment changes this inhibited state can alter. By altering the balance of activatory and inhibitory signaling, this then alters how likely platelets are to activate and form a thrombus. Understanding how platelet inhibition is corrupted by changes to the vascular environment is therefore key. This strand of research is completed alongside Dr Graeme Stasiuk, and Dr Monica Arman.
Project 2: Thrombiglow: 'Smart' Multimodal Platelet specific 'Theranostic' Drug Delivery Imaging Agents
This strand of research is completed in collaboration with Dr Graeme Stasiuk (King's College London). 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 research aims to use nanomaterials to design a drug therapy that would target platelets specifically, reduce side-effects such as bleeding, whilst maximising platelet inhibition, and so help to prevent thrombus formation.
Grants at present:
1) BHF PhD studentship (Co-PI) " Effect of hypoxia on prostacyclin-mediated inhibition of platelet function” (£110,353) 2022-2025 (with Dr Monica Arman (PI)). This project is a non-clinical PhD studentship that is in collaboration with Dr Monica Arman (PI). Tissue hypoxia occurs in multiple cardiovascular and pulmonary conditions including myocardial infarction, stroke, chronic obstructive pulmonary disease (COPD) and sleep apnoea. However, knowledge on how human platelets function in hypoxic (low oxygen) conditions is lacking. Our group is interested in understanding how hypoxia affects platelet inhibition, specifically endothelial-released prostacyclin (PGI2) and its downstream intracellular signalling.
2) MRC New Investigator Award (co-PI) “Matrix metalloproteinase activated Multimodal 'Theranostic' Drug Delivery Imaging Agents for thrombosis” (£679,625) 2020-2024 (With Graeme Stasiuk)This project will drive the development of a nanoparticle based stroke therapy. The nanoparticle is designed to bind the clot specifically to deliver the drug in a specific and directed manner, whilst also having optical capability to monitor clot dissolution.
3) BHF PhD studentship (PI) “Is Zinc critical for the control of platelet cyclic nucleotide signalling? (£108,240) 2019-2022. This project is a non-clinical PhD studentship funded to understand how the inhibitory signalling induced by the cyclic nucleotides, prostacyclin and nitric oxide, is changed by the presence or absence of zinc.
Present lab members
Leigh Naylor-Adamson: MRC funded PDRA
Charlie Coupland (PhD): BHF student 2019-2022
Zoe Booth (PhD): University of Hull studentship 2019-2022
Michelle Kinnon (PhD): BHF student 2017-2020 (PI Graeme Stasiuk)
Past lab members
Muhammad Yusuf: PhD awarded 2017
Lloyd Atkinson (PhD): PhD awarded 2018
Yusra Ahmed (PhD): PhD awarded 2021
I am responsible for the MSc in Pharmacology and Drug Development at Hull York Medical School. This MSc aims to provide students with a unique and unrivalled opportunity to immerse yourself in the clinical, basic science and industrial aspects of pharmacology.
The MSc programme is built around core modules that cover the fundamental principles of pharmacology and the clinical relevance of drugs for the major organ systems, whilst demonstrating the drug development process, from initial drug design to understanding the fundamental importance of clinical trials.
The teaching is given from experts in their field including our own clinical trials unit as well as invited speakers from internationally relevant drug companies and the Home Office. If you would like more information on this MSc please email me directly.
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.
Dr Graeme Stasiuk (King's College London)
Graeme is a chemist. We work together on both MRC and BHF funded research projects.
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.
My present PhD students are funded by the British Heart Foundation, and also a University of Hull internal studentship.
I am the external examiner for the MBChB graduate entry program at Birmingham University.