PhD: Complement dysregulation as a driver of microvascular injury in cardiogenic shock

About the Project

Project summary:

Shock is a severe, life-threatening condition caused by critically reduced blood flow to tissues and organs and remains a major cause of death and disability in intensive care. A central feature of shock is endothelial dysfunction, leading to vascular leakage, tissue oedema, and multi-organ failure. Emerging evidence indicates that dysregulation of the complement system, a key component of innate immunity, contributes to this process by driving inflammation, amplifying coagulation, and promoting vascular injury. However, the precise complement pathways involved in cardiogenic shock (CS) and the prognostic value of circulating complement biomarkers remain unclear. This project will address these gaps by profiling complement dysregulation in CS using a comprehensive biomarker panel. The work will define the complement pathways driving vascular injury, identify predictive biomarker signatures, and highlight novel therapeutic targets to improve outcomes in critically ill patients.

Research plan

The student will analyse complement dysregulation in shock with the following aims:

Aim 1: Quantify complement components, regulators, and activation markers using 25 in-house complement assays (ELISA and/or MSD) in plasma from a unique cohort of >350 patients with cardiovascular shock, collected at Barts Health NHS Trust (Barts), alongside matched healthy controls.

Aim 2: Integrate complement biomarker data with clinical outcomes and biochemical measures (e.g. troponin, lactate, syndecan-1, vascular cell adhesion molecule-1 (VCAM-1)) to identify signatures associated with endothelial dysfunction and disease severity.

Aim 3: Develop predictive biomarker models using statistical and pathway analyses to identify marker sets associated with mortality, prolonged intensive care unit (ICU) stay, persistent organ dysfunction, and where longitudinal data permit (vascular cognitive impairment and vascular dementia) relevant outcomes, forming the basis for future vascular dementia; focused biomarker and therapeutic studies.

Techniques and training

The student will receive technique-rich training in complement immunoassays (ELISA, MSD), biomarker discovery pipelines, and translational cardiovascular immunology. They will gain experience in advanced biostatistics and machine-learning approaches (e.g. PCA, clustering, random forest) using R and Python, alongside assay development to industry standards, including analytical validation, quality control, and exposure to regulatory frameworks (ISO13485, IVDR principles). The student will be embedded within the Division of Infection and Immunity and the Cardiff Dementia Research Institute (DRI), a highly collaborative environment with a strong ECR network. They will be registered in the School of Medicine and supported by cross-school supervision and collaboration with the School of Biosciences, providing access to complementary expertise, facilities, and training opportunities.

Supervision and environment

The project will be jointly supervised by experts in complement biology, cardiovascular science, and data science:

Impact and career development

This project offers excellent interdisciplinary training at the interface of academic science, clinical medicine, and industry. It is well positioned to generate high-quality pilot data suitable for future BHF or NIHR applications and to deliver impactful research outputs relevant to cardiovascular and immunology research. The student will develop a robust skillset spanning complement biology, vascular inflammation, quantitative biomarker science, and statistical modelling, providing a strong foundation for a career in academia, translational research, or the biotech/pharmaceutical sector.

How to apply:

You can apply online - consideration is automatic on applying for a PhD with an October 2026 start date.

 Please use our online application service at: https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/pharmacy

Key details

• Location UK DRI at Cardiff
• Salary: This Wales Heart Research Institute Cardiovascular Fund studentship is open to Home and EU applicants. The award offered will cover fees and a maintenance stipend (for 26/27 this will be approx. £21,300).