About the Project

Lymphatic vessel dysfunction: an unrecognised contributor to viral haemorrhagic diseases

Viral haemorrhagic diseases, including severe dengue, remain a major global health challenge, affecting hundreds of millions of people each year and causing significant morbidity and mortality worldwide. Dengue virus infection can progress to a life-threatening condition characterised by bleeding, shock and pathological fluid accumulation in tissues. While disruption of blood vessel integrity has been widely studied as a driver of these symptoms, far less attention has been paid to the lymphatic system, which plays a fundamental role in draining excess tissue fluid and regulating immune responses during infection.

Recent work from our group has revealed, for the first time, that the dengue virus non-structural protein NS1 directly damages lymphatic endothelial cells, impairing their barrier function and disrupting lymphatic vessel integrity. These findings identify lymphatic dysfunction as a previously unrecognised contributor to dengue haemorrhage. This PhD project will build on these discoveries to define how lymphatic vessel impairment contributes to fluid accumulation, inflammation and disease severity in viral haemorrhagic infections.

By integrating vascular biology, immunology and bioengineering, the project will investigate how dengue virus components alter lymphatic permeability, disrupt interactions with perivascular smooth muscle cells, and impair immune cell trafficking during infection. Together, these mechanisms are expected to drive excessive inflammation and defective fluid clearance in severe disease.

This interdisciplinary PhD in Biosciences and Medicine will be jointly supervised by Dr Paola Campagnolo and Dr Matthew Siggins, experts in vascular biology and immunity, and Dr Kevin Maringer at the Pirbright Institute, an expert in virology. This programme will provide comprehensive training in cell biology, vascular tissue engineering, microfluidics, and translational disease modelling and has broader implications for other viral haemorrhagic diseases and conditions associated with lymphatic failure, including cancer and chronic inflammatory disorders.

Key references:

• Puerta-Guardo H et al. Cell Rep (2019) – Flavivirus NS1 and vascular dysfunction
• Cheung Y et al. MSphere (2020) – Role of perivascular cells in dengue vascular leakage
• Abukunna F et al. BiorXiv (2026) – Lymphatic vessel dysfunction in severe dengue