Around 12 million people in the UK are diagnosed with respiratory diseases such as obstructive pulmonary disease, respiratory distress syndrome and pulmonary hypertension. Patients with respiratory disease suffer from a range of pathologies, such as hypoxia and pulmonary edema, associated with cardiovascular complications and increased mortality. One of the hallmarks of this group of diseases is disruption of the pulmonary microvasculature however despite significant efforts in the field, there is still no effective treatment to reduce this injury in patients with respiratory disease.
In respiratory diseases, there is an increase in oxidative stress and actin remodeling in the pulmonary endothelium, resulting in breakdown of the vasculature. We have identified a novel protein in the pulmonary endothelium, p18/LAMTOR1, which is downregulated in respiratory disease models. Proposed studies are needed to understand the mechanism through which this novel protein maintains a healthy endothelium. The research question for this PhD project is therefore: does p18/LAMTOR1 regulate oxidative stress and actin remodelling in the pulmonary endothelium? Proposed studies will address a new area of research which will develop our understanding of p18/LAMTOR1 in the endothelium and provide data to support a potential therapeutic target to improve microvascular function in patients with respiratory diseases.
Research will be performed using a range of in vitro techniques with healthy pulmonary arterial endothelial cells (HPAEC) to measure the role of p18/LAMTOR1 in regulating oxidative stress, actin remodeling and barrier function in the pulmonary endothelium.
Findings are anticipated to establish p18/LAMTOR1 as a key protein which regulates the pulmonary endothelium. The PhD will give insight into the mechanism through which p18/LAMTOR1 maintains the endothelium and expand our understanding of the novel role of the protein in the lung. Studies are anticipated to implicate p18/LAMTOR1 as a therapeutic target in maintaining a healthy endothelium.