Dr Mike Wilson
What we do
Our work focusses on exploring the pathophysiology underlying acute respiratory distress syndrome (ARDS) using a variety of preclinical in vitro and in vivo approaches. Importantly, ARDS is not a disease, rather it is a complex clinical entity which may be triggered by various pathologies such as infection (either within the lungs, eg. COVID-19, or within the rest of the body, eg. sepsis) or trauma. Fundamentally ARDS is a result of an inappropriate or overwhelming inflammatory response to such insults. Our research is designed to understand this inflammatory response and how it subsequently leads to physiological failure of the lungs and other organs.
Why it is important
ARDS is commonly found within critically ill patients, historically associated with ~10% of all Intensive Care Unit admissions and ~23% of mechanically ventilated patients. The importance of ARDS has been particularly highlighted recently during the COVID-19 pandemic, with up to 2/3 of severely ill patients designated as having developed ARDS, among who it is the main cause of death. Mortality from ARDS is extremely high, ranging from 20-45%, and crucially there are very few therapeutic options aside from treating underlying infections (if present) and organ support until recovery. These supportive treatments (eg. mechanical ventilation, extracorporeal organ support) are however not risk-free and may introduce complications of their own.
How it can benefit patients
We believe that by utilising our range of preclinical models of injury we can better understand the biological processes underlying ARDS itself, and the iatrogenic injury that can occur during treatment. By understanding these processes, we hope to be able to develop therapeutic strategies that can improve both mortality and quality of life among survivors.
Summary of current research
- Ventilator-induced lung injury: While mechanical ventilation is a mainstay of treatment for patients within thin Intensive Care Unit, it can induce iatrogenic injury, known as ventilator-induced lung injury (VILI) which has a major impact on the outcome of patients. We use models of in vitro cell stretch and an internationally recognised in vivo set-up to investigate VILI, from its initiation to its consequences.
- Inter- and Intra-cellular signaling: Communication between cells, and signaling pathways within cells are crucial determinants in the inflammatory response during ARDS and VILI. We have previously shown that the proinflammatory cytokine tumour necrosis factor- a has opposing effects during models of ARDS/VILI depending on which cell surface receptor it acts through. Intriguingly it seems as though the cellular consequences of TNF receptor signaling vary depending on the nature of the initial insult, a phenomenon we are currently exploring. We have also recently identified a new mediator of VILI named cyclophilin A. As part of these investigations we demonstrated for the first time that cyclophilin A is dramatically increased in the lungs of ARDS patients (and as a side-note may be involved in SARS-CoV2 infectivity), indicating that this may be a potential future therapeutic target. We are currently investigating the mechanisms by which this mediator is secreted, and whether it may play a role in long-term consequences of critical illness.
- Propagation of inflammation: One of the most interesting aspects of ARDS is that while patients enter, and remain within, ICU due to respiratory problems, they primarily die due to multiple organ failure. The mechanisms by which this occurs remain unclear, but mechanical ventilation seems to play a crucial role. Understanding the reasons behind this systemic propagation of injury/inflammation is a major aspect of our work, and we have recently been awarded an MRC-funded project grant to explore a possible novel mechanism.
- Professor Uta Greissenbach (Faculty of Medicine)
- Professor Eric Alton (Faculty of Medicine)
- Dr Fiona Culley (Faculty of Medicine)
- Prof Danny McAuley (University of Belfast)
- Dr Cecilia O’Kane (University of Belfast)
- Dr Matthieu Jabaudon (University of Clermont-Auvergne)
- Prof Tony Pickering (University of Bristol)
- Dr Mike Ambler (University of Bristol)
- Miss Rhianna Baldi
- Dr Nikhil Tirlapur
- Dr Jonathan Stephens
Dr Michael Wilson
Dr Michael Wilson
Dr Chubicka Thomas
Dr Chubicka Thomas