Current research projects

Galectins are a family of carbohydrate-binding proteins that play critical roles in immune cell recruitment, vascular biology, and inflammatory disease. Our research focuses on understanding how specific Galectins act as molecular “traffic controllers”, shaping when and where immune cells enter tissues.

A major focus is Galectin-9, where we investigate its role in regulating monocyte recruitment during inflammation and its contribution to the progression and regression of atherosclerosis. Using both in vitro systems and in vivo disease models, we examine how endogenous Galectin-9 influences interactions between immune cells, platelets, and the vascular endothelium during thrombo-inflammation. This includes characterising the role of Galectin-9 in T-lymphocyte trafficking in inflammatory and autoimmune conditions, as well as its involvement in monocyte-platelet interactions that drive thrombo-inflammatory responses.

Beyond the vasculature, we are exploring the role of Galectins in inflammatory bowel disease (IBD) using state-of-the-art single cell sequencing and proteomic approaches. This allows us to identify which Galectins are active in diseased tissue, how they shape immune cell behaviour, and how their dysregulation contributes to chronic intestinal inflammation.

We also study how mechanical forces, such as blood flow and shear stress, regulate Galectin expression by endothelial cells. Understanding how vascular cells sense and respond to these forces is essential for explaining why inflammation develops in specific vascular regions and how this contributes to disease risk.

IL-17 is a powerful inflammatory cytokine increasingly recognised as a key driver of chronic inflammatory disease. Our research aims to define how IL-17 activates innate immune cells and how this signalling contributes to tissue damage across a range of inflammatory conditions.

We focus particularly on monocytes and macrophages, examining how IL-17 alters their activation state, intracellular signalling pathways, and inflammatory outputs. By dissecting these mechanisms, we aim to understand how IL-17 amplifies inflammation and sustains immune responses that fail to resolve.

Alongside mechanistic studies, we are developing novel reagents and tools to target IL-17 pathways. These approaches aim to refine therapeutic strategies by modulating harmful inflammation while preserving essential protective immune functions. This work contributes to a broader effort to identify new therapeutic targets within innate immune signalling pathways that are relevant across multiple inflammatory diseases.

PEPITEM – endogenous peptide regulator of immune and stromal responses in health and disease.

PEPITEM (Peptide Inhibitor of Trans-Endothelial Migration) is an endogenous immunomodulatory peptide that plays a fundamental role in controlling immune cell entry into tissues. Derived from the 14-3-3ζ protein and released from B cells, PEPITEM acts on endothelial and stromal cells to restrain inappropriate leukocyte entry into tissues and maintain immune balance.

Our research investigates how PEPITEM signalling becomes disrupted with ageing and in chronic inflammatory diseases such as rheumatoid arthritis, psoriatic disease, and type 1 diabetes. Loss of this regulatory pathway contributes to persistent inflammation and tissue damage. We are particularly interested in understanding the role of PEPITEM in regulating monocyte and macrophage function under both inflammatory and homeostatic conditions, as well as its pro-resolving actions during acute inflammation. Ongoing studies are also examining how PEPITEM modulates neutrophil activation and recruitment.

Recent work has expanded the role of PEPITEM beyond immune trafficking. We have shown that it also regulates bone remodelling, promoting bone formation while limiting bone loss, and plays a protective role in skin inflammation by suppressing pathological immune infiltration. These findings position PEPITEM as a unique homeostatic regulator acting across immune, stromal and parenchymal compartments.

Our current and future research seeks to define how PEPITEM signalling is integrated across tissues and how stromal cells shape local inflammatory niches through this pathway. In parallel, we are characterising the function of PEPITEM-derived tripeptides in vivo and developing stable peptide derivatives and peptidomimetics, advancing translational pipelines aimed at restoring endogenous regulatory mechanisms rather than simply suppressing inflammation.

Stromal cells (including fibroblasts, endothelial cells, and mesenchymal cells) form the structural and regulatory backbone of tissues, shaping how cells communicate to maintain health and how this balance is disrupted in disease. Once thought to be passive, these cells are now recognised as active regulators of inflammation, sensing mechanical, metabolic, and immune signals from their environment.

Our research explores how stromal cells coordinate immune responses and tissue repair in health, particularly within joint tissues, and how these same principles extend to other barrier sites such as the skin. In conditions such as rheumatoid arthritis, osteoporosis, psoriasis, and other inflammatory disorders, stromal cells can acquire maladaptive states that sustain inflammation and impair tissue regeneration.

A central question driving this work is how pathological stromal states are established and maintained, and whether they can be reset. We investigate how stromal cells encode inflammatory “memory”, how this alters immune cell recruitment and behaviour, and how ageing and chronic inflammation disrupt these communication networks.

By combining advanced multicellular models, patient-derived tissues, and translational approaches, our goal is to identify new therapeutic opportunities that target the tissue microenvironment itself. This strategy moves beyond symptom control towards restoring tissue homeostasis across a wide range of inflammatory diseases.

Damage-associated molecular patterns (DAMPs) are endogenous danger signals released from stressed or injured cells that play a central role in amplifying inflammation. Our research focuses on how DAMP-driven inflammation links disease processes between the lungs and the heart, helping to explain why pathology in one organ can trigger injury in the other.

A key focus is understanding COPD-induced cardiac damage, where chronic lung inflammation increases cardiovascular risk, and myocardial infarction (MI)-induced acute lung injury, where cardiac injury drives secondary inflammatory responses in the lungs. We are particularly interested in the role of DAMPs such as S100A8/A9, which are released during tissue injury and act as potent mediators of innate immune activation.

An important unanswered question is why inflammatory signals originating in one organ preferentially target specific distant organs while sparing others, a phenomenon known as immune organotropism. We investigate how DAMP signalling, immune cell trafficking, and vascular microenvironments determine organ-specific vulnerability following cardiac or respiratory disease.

By combining a wide range of state-of-the-art experimental and translational approaches, including in vivo intravital imaging of the beating heart and breathing lungs, pre-clinical disease models, ex vivo patient-derived systems, and advanced single-cell sequencing and proteomic analyses, we aim to identify novel biomarkers for patient stratification and uncover new therapeutic targets.