Lindsay Jefferson

2024 Paroian Family PH Research Scholarship

Queen’s University, Department of Medicine, Translational Medicine Graduate Program

Under the supervision of: Dr. Stephen Archer

About Lindsay Jefferson

Lindsay is a second-year translational medicine MSc student at Queen's University, supervised by Dr. Stephen Archer. She earned a Bachelor of Science (Honours) in Life Sciences with distinction from Queen's University in 2023. Her research aims to learn more about the mechanism of pulmonary arterial hypertension (PAH) and right-ventricular failure (RVF), the leading cause of death in pulmonary arterial hypertension. Using a rat model, her project examines whether right-ventricular failure is partly a consequence of inflammation, how this inflammation relates to a specific metabolic action, whether there are sex differences in inflammation and metabolism in PAH, and whether a particular molecule has therapeutic potential. Lindsay aspires to be a clinician-scientist in the pulmonary hypertension field.

Project:

Investigating the immunometabolism of macrophages in the right ventricle in pulmonary arterial hypertension (PAH)

Although it is conventionally believed that the right heart failure in pulmonary arterial hypertension is due to high pulmonary vascular resistance (afterload), we have evidence that it is driven in part by inflammation, meaning an invasion of white blood cells that damage the heart. While pulmonary arterial hypertension is more common in females, males have lower survival due to worse right heart adaptation. We want to learn how inflammation happens in the right heart, understand a possible metabolically mediated sex difference in the inflammatory response, and test a potential metabolic therapy. We will study inflammatory cells called macrophages in a PAH rat model. Comparing males and females, we will learn how sex hormones affect inflammation in PAH. We will also test a drug that changes how sugar is processed in the macrophages as a metabolic therapy to lower inflammation and improve heart function.

The findings of this project will contribute to the understanding of the role of metabolic abnormalities in the inflammation leading to right ventricular failure in pulmonary arterial hypertension. We will also gain valuable knowledge about the metabolic control of inflammatory cells and how it plays out in the sexual dimorphism of right ventricular failure in PAH, while testing a novel metabolic therapy which has previously been used safely in humans.