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.

Project Background

Heart failure remains a leading cause of morbidity and mortality worldwide, intrinsically linked to 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. 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 several pre-clinical cardiac models and clinical studies. Therapies focused on reducing mechanical forces in the myocardium, including profound mechanical unloading by left ventricular assist devices (LVADs), have been shown to promote reverse remodeling, 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. 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 investigate how mechanical forces affect the regenerative capacity of the heart, aiming to identify mechano-biological mechanisms for therapeutic application. The research will span multiple experimental models, including in vitro cellular systems, engineered cardiac constructs, living myocardial slices, whole explanted hearts, and animal models of cardiac unloading. The PhD candidate will also have access to cardiac samples and datasets from patients undergoing LVAD-mediated mechanical unloading.

Key Objectives

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

Research Environment

This research is embedded in Drive-RM, a large national research consortium focused on regenerative medicine. The PhD candidate will work at the Experimental Cardiology lab of UMC Utrecht and have access to state-of-the-art platforms and technologies at the Regenerative Medicine Center Utrecht and the Department of Medical Physiology. The candidate will join a stimulating and interdisciplinary research environment at the intersection of cardiac biology, biomechanics, and regenerative medicine, working closely with clinicians from the departments 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.

Candidate Profile

We are seeking a highly motivated, curious, and independent researcher with a MSc degree and a strong collaborative mindset, able to 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 is considered advantageous.

Benefits

• 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.
• Opportunities for personal and professional development.
• Year-end bonus of 8.3% and holiday allowance of 8%.
• Pension insurance with ABP, with approximately 70% of the monthly contribution covered.
• 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).

Submit your application including your CV, a motivation letter, and two reference letters to v.m.sampaiopinto@umcutrecht.nl and j.sluijter@umcutrecht.nl.