PhD Position on Driving forces in cardiac regeneration

This PhD project will explore how mechanical forces affect the regenerative capacity of the heart, with the ultimate goal of identifying mechano-biological mechanisms that could be harnessed for therapy.

Dit ga je doen

Heart failure remains a leading cause of morbidity and mortality worldwide, which is intrinsically linked with the very limited regenerative capacity of the adult human heart. Unlike lower vertebrates, adult mammalian cardiomyocytes proliferate minimally after injury, leading to maladaptive remodeling and progressive dysfunction. However, there is growing evidence that mechanical cues strongly influence myocardial biology. Mechanical overload contributes to pathological remodeling, while mechanical unloading can favor cardiomyocyte cycling and promote cardiac regeneration. These observations span across several pre-clinical cardiac models up to clinical studies. A number of therapies focused on reducing the mechanical forces in the myocardium, including profound mechanical unloading by left ventricular assist devices (LVADs), have been shown to promote reverse remodeling. This process is characterized by normative changes at the structural, molecular, and functional levels. In rare cases, myocardial reverse remodeling is so pronounced that it allows for device explantation. Hence, while some evidence suggests that mechanical therapy can significantly improve patient outcomes, the precise mechanisms driving reverse remodeling upon unloading and the link with cardiac regeneration remain elusive.

Project description
This PhD project will explore how mechanical forces affect the regenerative capacity of the heart, with the ultimate goal of identifying mechano-biological mechanisms that could be harnessed for therapy. The work will span multiple experimental models, from in vitro cellular systems, engineered cardiac constructs, living myocardial slices, whole explanted hearts and animal models of cardiac unloading. Complementing these experimental approaches, the PhD candidate will have access to cardiac samples and datasets from patients undergoing LVAD-mediated mechanical unloading.

Key objectives include:

• Dissecting the cellular and molecular mechanisms by which mechanical forces regulate cardiomyocyte proliferation, survival, and function.
• Characterizing regenerative responses in biomimetic platforms such as engineered heart tissue and myocardial slices under controlled loading and unloading conditions.
• Investigating molecular signatures of reverse remodeling in human cardiac tissue and patient-derived data.

Hier ga je werken

This research is embedded in Drive-RM (https://drive-rm.nl), a large national research consortium, focused on regenerative medicine. The PhD candidate will work at the Experimental Cardiology lab of the UMC Utrecht and have access to state-of-art platforms and technologies at the Regenerative Medicine Center Utrecht and the department of Medical Physiology. The candidate will work in a stimulating and interdisciplinary research environment, at the intersection of cardiac biology, biomechanics, and regenerative medicine, and in close contact with clinicians of the department of cardiology and cardiothoracic surgery. This is a unique opportunity to contribute to a transformative area of medicine and develop novel regenerative therapies for human heart disease.

Dit neem je mee

We are seeking for a highly motivated, curious, and independent researcher with a MSc degree, strong collaborative mindset that can thrive in an international translational research environment. The candidate must be proficient in spoken and written English and have a solid background in biomedical sciences, physiology, biology, or a related field. Experience in cardiac biology, molecular biology and cell culturing are considered advantageous.

Are you the person we are looking for? Submit your application including your CV, a motivation letter and two reference letters to [email protected] and [email protected]

Dit bieden we jou

• A salary between € 3108 - € 3939 gross per month (salary scale OIO), based on full-time employment (36 hours).
• Access to advanced models, technologies, and patient-derived material.
• Comprehensive training and mentoring within a collaborative international network.
• Possibilities to develop yourself personally and professionally.
• Year-end bonus of 8.3% and holiday allowance of 8%.
• Pension insurance with ABP. We take care of approximately 70% of the monthly contribution.
• Public transport reimbursement.
• The option to select additional employment benefits in exchange for gross salary, such as purchasing a bicycle and memberships (Cao á la carte).