In-depth functional characterization of arrhythmogenic vulnerability in the infarct border-zone

At the Department of Cardiovascular Sciences, you will work under the combined supervision of profs. P Claus (Lab of Cardiovascular Imaging and Modeling) and E Dries (Lab of Experimental Cardiology) in close collaboration with the clinical electrophysiology department of the university hospitals UZ Leuven (profs. B Vandenberk and R Willems). During the course of the project other (international) collaborators will be involved.

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Project

The general project

Sudden cardiac death (SCD) is the second leading cause of death after all cancers combined in Western society. The incidence of SCD is estimated to be as high as 400 000 deaths/year in Europe. Lethal ventricular arrhythmia such as ventricular tachycardia (VT) and ventricular fibrillation (VF) underlie the vast majority of unexpected SCD. 

Up to 70% of these SCDs are related to myocardial ischemia or infarction and subsequent heart failure as an underlying structural cardiac abnormality.

Previous work within our research groups has shown that the ventricular arrhythmias find their origin in specific localized regions within the border zone of the myocardial scar and we have studied these at several levels ranging from in-vivo phenotyping of the electrophysiology to the cellular properties of the different cell types (with focus on cardiac myocytes and fibroblasts) constituting these regions down to the gene expression level with sn-RNASeq. The latter study revealed a prominent role of differentially expressed genes involved in mechano-electrical coupling.

Therefore we set out to study the impact of these differences in expressions for stretch-sensitivity of the infarct border zone and therefore their relevance  for arrhythmogenesis in the intact in-vivo large animal model together with a deep phenotyping, and studying that further in a controlled way in living myocardial slices with controlled stretch and the possibility of testing pharmacological interventions, including genetic modifications involving these identified genes.  

The PhD project

As a PhD student, you will be involved in managing the large animal model, with associated phenotyping with multi-modal medical imaging, including PET imaging, magnetic resonance imaging and echocardiography, combined with electrophysiology mapping. In vivo studies will identify localized arrhythmogenic regions, which will be sampled for ex vivo investigations using myocardial tissue slices. You will get support from our lab technician and a post-doc involved in technical developments. Additionally, you will use and further refine the living myocardial slice technique to include a mechanical stretch testing setup.

Profile

We are looking for a highly motivated young researcher with a Master degree (or equivalent) in Biomedical or Life Sciences, Bioscience Engineering, Medicine, Biology or related disciplines, willing to study and do research at the leading edge of biomedical engineering.

Candidates have excellent teamwork and communication skills and are enthusiastic about collaborating with a diverse range of international partners. We expect them to be fluent in English as this will be the language used to interrelate with the different partners. Candidates should be able to work independently as well as in a team and have a problem-solving attitude.

On the basis of this project, a training plan will be set up by selecting the best training opportunities in the PhD programme of KU Leuven and available initiatives within our collaborators. Further physiology training will be organized depending on the needs and background of the researcher and the project and you are expected to join and lead discussion groups. The candidate is expected to write a doctoral thesis within 4 years.

Our research group wants to focus on translational research, working closely together with the academic clinical center. Therefore, our group provides methodologies and offers support for clinical and basic researchers to help to define the research approach from the basic understanding of the disease towards the clinical study; to select/design the appropriate investigational tools to assess the relevant physiological  parameters; and to interpret the results and relate them to the pathophysiological knowledge. 

Offer

We offer a 4 year PhD scholarship to work on an international an interdisciplanary environment, to allow you to work at the forefront of science. This is embedded in a doctoral school that will enable you to enlarge your personal skills.  

Interested?

For more information please contact Prof. dr. Piet Claus, tel.: +32 16 34 90 17, mail: [email protected] or Prof. dr. Eef Dries, tel.: +32 16 37 94 54, mail: [email protected].

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