Andrietta Sofie Grentzmann - PhD Scholarship 2022

Project summary:
The role of the metabolic enzyme PDK1 in cardiovascular diseases

Cardiovascular diseases (CVDs) are mainly caused by atherosclerosis, a chronic inflammatory disease of the artery wall. We have found evidence that a small metabolic enzyme, pyruvate dehydrogenase kinase-1 (PDK1), is associated with CVD burden in humans. My project aims to systematically investigate immunometabolic reactions driven by PDK1, in immune and vascular cells, with the potential to reveal a new target for therapies or a novel biomarker for CVD disease progression and complications.

Project title

The role of pyruvate dehydrogenase kinase-1 in cardiovascular diseases

Background

Atherosclerosis is a chronic inflammatory disease driven by maladaptive immune responses. Novel insights into immune processes have revealed that changes in intracellular metabolism can strongly affect inflammation. Pyruvate dehydrogenase kinase-1 (PDK1) has been identified as a major metabolic enzyme regulating immune cell activation. Preliminary data from Prof.Ketelhuth’s group suggest that PDK1 expression/activity is associated with symptomatic atherosclerotic disease.

Aim and methods

In my project, I will use cell culture systems, genetically-modified animal models of disease, as well as unique human peripheral blood samples to investigate PDK1-driven mechanisms in deep detail and evaluate its potential for modulating experimental atherosclerosis, as well as its potential as a biomarker for disease progression and/or complications. Better understanding of the molecular mechanisms driving atherosclerosis will help accelerate the development of new diagnostic modalities, as well as new therapies against major life-threatening diseases, including myocardial infarction and stroke, the major cause of death worldwide.