Dr Amanda Unsworth

Profile

I completed my degree at the University of Oxford, in Molecular and Cellular Biochemistry (MBiochem) in 2008. I continued my postgraduate studies (DPhil) at the University of Oxford in the laboratory of Dr Catherine Pears investigating the role of the novel Protein kinase C isoforms in platelet function in a collaborative project with Professor Steve Watson at the University Birmingham, funded by the British Heart Foundation (Awarded in 2012). After a short postdoctoral research position in Oxford investigating the role of ubiquitination in the regulation of platelet signalling events, in 2013 I joined the lab of Professor Jon Gibbins at the University of Reading. Between 2013 and 2019 I worked as part of a British Heart Foundation Programme grant team to investigate the signalling pathways involved in negatively regulating platelet function and thrombosis and how these lead to differences in platelet reactivity in the population. In 2019 I joined Manchester Metropolitan University as a Lecturer in Haematology, delivery teaching on the Biomedical Science undergraduate degree and specialist Haematology and Transfusion MSc. In 2020 I completed a postgraduate certificate in Teaching and Learning in Higher Education (PGCertTLHE) and gained Fellowship of the Higher Education Academy. In addition to teaching, I also managed a research group, and was awarded research funding from the British Heart Foundation,and the Royal Society to investigate mechanisms leading to thrombosis. In 2023 I was awarded a Professor Heimburger Award from CSL Behring. I joined the Leeds Institute of Cardiovascular and Metabolic Medicine at the University of Leeds in the summer of 2024. I am currently Chair of the Platelet Society.

Research interests

Inflammation is associated with increased risk of cardiovascular disease and thrombotic events. Platelets are initiators and drivers of arterial thrombosis, and inflammation is associated with dysregulated platelet production, platelet hyperreactivity and increased thrombus formation. The aim of my lab’s research is to understand how inflammatory signalling molecules and pathways lead to thrombosis. To do this we are using a multicellular approach, investigating how these signalling cascades are altered in the different cell types that contribute to thrombosis in the vasculature. We are also particularly interested in how inflammation may drive changes in the bone marrow that lead to the production of phenotypically prothrombotic platelets.   We hope that in understanding the contributions of these pathways will enable the identification of drug targets that can be used for the treatment of and prevention of cardiovascular disease.

Current projects:

Investigating Pim kinase in the regulation of thrombosis. Pim kinase is family of serine/threonine kinases that are associated with inflammation and malignancy. We have identified anti-thrombotic properties of Pim kinase inhibitors. We are currently working on dissecting the mechanisms by which Pim kinase regulates megakaryocyte, platelet, leukocyte and endothelial cell function to contribute to thrombosis.

Characterising the role of Ubc13 in the regulation of megakaryocyte and platelet function: Post-translational modifcations are essential for the propagation of signalling events. In platelets (and most cell types) the most widely understood of these is phosphorylation. However, there is increasing evidence in platelets that ubiquitination is important for transmission of platelet signalling. This project is focussed on investigating the role of Ubc13 and E2 ligase in the regulation of megakaryocyte and platelet signalling events and function. 

Inflammation driven reprogramming of megakaryocyte and platelet function: We are also examining whether the changes to the inflammatory environment and blood leads to reprogramming of megakaryocytes within the bone marrow and the production of phenotypically altered platelets that are prothrombotic and predisposed to thrombosis. 

Our work is supported through research grants from the British Heart Foundation and CSL Behring. 

Qualifications

• DPhil in Biochemistry, University of Oxford
• MBiochem, University of Oxford
• PGCertTLHE, Manchester Metropolitan University

Professional memberships

• The Platelet Society
• British Society of Haemostasis and Thrombosis
• International Society of Thrombosis and Haemostasis
• Biochemical Society

Student education

MSc Cardiovascular Health and Disease

PhD Student supervision

Research groups and institutes

• Leeds Institute of Cardiovascular and Metabolic Medicine