Translating Animal Immunothrombosis Signatures into Human Clinical Guidance: The Role of Venous Insufficiency and Stenosis

About the Project

In human patients, venous thromboembolism (VTE) is a major cause of mortality, often driven by altered haemodynamics in the context of venous insufficiency and stenosis. Notably, coronary artery stenosis (CAS) caused by atherosclerotic disease may predispose individuals to venous thrombosis,[1] suggesting a systemic link between arterial pathology and venous risk. Evidence suggests that reduced blood flow enables a prothrombotic vicious circle where IgM and IgG deposition triggers complement activation and platelet recruitment.[2] This is exacerbated by chronic infections leading to antibody inflation.[3], [4], [5] This project addresses the translational gap by analysing molecular signatures from animal models, comparing antithrombotic treatment against controls, to identify how drug efficacy is modulated by flow conditions and immune status. By integrating these signatures with imaging datasets of stenotic vessels,[6] we will build 3D Digital systems to simulate how vascular stasis interacts with antibody levels to trigger VTE.

Aims and objectives:

1. To identify molecular signatures of antithrombotic response in animal models and characterise their variation in relation to flow-stasis and immune profiles.
2. To investigate how venous insufficiency, stenosis, and systemic factors linked to CAS facilitate antibody-driven thrombosis (IgM/IgG/Complement) using 2D/3D in vitro flow models.
3. To develop a 3D Digital Twin framework that utilises human MRI to simulate the impact of vascular geometry on immunothrombosis, enabling clinical guidance.

Methods:

• Bioinformatic pipeline comparing animal datasets (antithrombotic vs. control) to identify biomarkers of treatment success modifiable by flow conditions and immune shifts.
• Development of 3D cell models (endothelial/platelet co-cultures) to study the vicious circle of IgG/IgM deposition under flow conditions mimicking venous insufficiency and stenosis.
• Quantify antibody titers and validate protein-level expression of FcμR and pIgR receptors in relation to immune-driven antibody inflation.
• Processing human MRI data (e.g., Phase-Contrast MRI) to extract vascular geometries from patients with venous insufficiency and CAS.

Using the Digital systems to model how different grades of stenosis and immune profiles interact to accelerate thrombus formation, enabling personalised clinical guidance for intervention.

Supervisors: Prof Melanie Hezzell and Dr Tim Dong

How to apply:

Please make an online application for this project at http://www.bris.ac.uk/pg-howtoapply. Please select <*programme title>* on the Programme Choice page. You will be prompted to enter details of the studentship in the Funding and Research Details sections of the form. In the funding section of the application form, select ‘Studentship’ as the main source of funding and enter *‘Studentship title’*.

Candidate requirements:Standard University of Bristol eligibility rules apply. Please visit PhD Veterinary Sciences | Study at Bristol | University of Bristol for more information.

Contacts: please contact fohs-pgadmissions@bristol.ac.ukwith any queries about your application. Please contact the project supervisor for project-related queries: Melanie Hezzell (mh16511@bristol.ac.uk)

Start date: September 2026

Funding Notes

This project is unfunded, so only available to self-funding students. Overseas students are welcome to apply but must be able to fund the difference between UK and Overseas tuition fees. Optional bench fees £5000 to allow additional lab work, but not essential.