Deciphering the immune architecture of human atherosclerosis

PROJECT OVERVIEW

Are you fascinated by how immune and metabolic responses shape cardiovascular disease?

The immune system is integral to the cardiovascular health and disease. Targeting inflammation ameliorates cardiovascular outcomes. Atherosclerosis, the underlying cause of cardiovascular disease, is conceptualised as a lipid-driven inflammation. Obesity has emerged as one of the strongest risk factors for heart attack, stroke and peripheral arterial disease, yet we still do not understand how chronic metabolic dysfunction reshapes immune responses within the arterial wall. As obesity becomes increasingly prevalent worldwide, uncovering the mechanisms linking metabolic health to cardiovascular disease represents one of the major challenges in modern medicine.

Over the past decade, advances in single-cell technologies have transformed our understanding of human atherosclerosis. Our previous work transformed our understanding of vascular immunity by identifying previously unrecognised macrophage populations that regulate vascular homeostasis and plaque progression. Together with subsequent studies revealing unexpected diversity among vascular lymphocytes, these discoveries demonstrated that the arterial wall contains a remarkably complex immune ecosystem. However, immune cells do not act in isolation. Their spatial organisation, interactions with neighbouring vascular and stromal cells, and relationship with clinical characteristics remain largely unexplored.

This highly translational DPhil project will investigate how metabolic dysfunction remodels the immune architecture of human atherosclerosis using a unique collection of freshly obtained carotid and femoral endarterectomy specimens from patients undergoing vascular surgery, together with matched blood and adipose tissue collected. By integrating these complementary tissues, we will determine how systemic metabolic health influences local immune responses within different vascular beds and contributes to plaque progression and clinical outcomes.

The student will combine state-of-the-art single-cell transcriptomics, spatial transcriptomics, multiplex tissue imaging and advanced computational biology to construct an integrated, spatially resolved atlas of the immune landscape in human cardiovascular disease. Rather than studying individual immune populations in isolation, the project will define how macrophages, lymphocytes and other immune and stromal cells interact within specialised tissue niches, how these cellular networks are remodelled by metabolic disease, and how they associate with plaque stability, cerebrovascular events and peripheral arterial disease.

By integrating molecular discoveries with detailed clinical phenotyping, this project will reveal fundamental mechanisms linking metabolic dysfunction with cardiovascular disease, identify new cellular pathways that underpin vascular inflammation, and provide a framework for future precision immunotherapies targeting cardiovascular disease.

Join our team in creating one of the world's most comprehensive spatially resolved atlases of human atherosclerosis. By combining unique clinical samples with advanced systems immunology, you will help uncover how the immune architecture of the arterial wall is remodelled in cardiovascular disease and contribute to discoveries that could transform the prevention and treatment of heart attack, stroke and peripheral arterial disease.

KEYWORDS

Cardiovascular Immunology
Atherosclerosis
Metabolic Disease
Spatial Biology
Single-cell Genomics

TRAINING OPPORTUNITIES

This interdisciplinary project combines vascular surgery, clinical medicine, immunology, computational biology and cutting-edge spatial multi-omics, providing exceptional training in translational cardiovascular research.

KEY PUBLICATIONS

Engelen SE, Robinson AJB, Zurke YX, Monaco C. Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed? Nature Reviews Cardiology (2022).

de Winther MPJ, Bäck M, Evans P, Gomez D, Goncalves I, Jørgensen HF, Koenen RR, Lutgens E, Norata GD, Osto E, Dib L, Simons M, Stellos K, Ylä-Herttuala S, Winkels H, Bochaton-Piallat ML, Monaco C. Translational opportunities of single-cell biology in atherosclerosis. European Heart Journal (2022).

Park I, Goddard ME, Cole JE, et al. C-type lectin receptor CLEC4A2 promotes tissue adaptation of macrophages and protects against atherosclerosis. Nature Communications 13, 215 (2022).

Dib, L., Koneva, L.A., Edsfeldt, A. et al. Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications. Nature Cardiovascular Research 2, 656–672 (2023).

THEMES

Immunology

Cardiovascular Science

Systems Biology

Translational Medicine

CONTACT INFORMATION OF ALL SUPERVISORS

Claudia Monaco 

Ashok Handa 

Stephen Sansom 

Aleksandra Boikova 

Emmanouil Solomonidis