Projects
3D vascularized cardiac organoid on-chip for modeling of dytropic and mitogenic cardiomyopathy. KU Leuven
In this project, we aim at generating 3D vascularized human cardiac organoids on-chip as unprecedented in vitro disease model to unravel novel molecular mechanistic insights on the pathogenesis of Duchenne Muscular Dystrophy (DMD)- and Alström Syndrome (ALMS)-associated cardiomyopathy. The 3D organoids will be generated via an autonomous cell aggregation process using a medium-throughput multi-microwells platform, and the disease phenotypes ...
Spatially-Organized 3D Human Cardiac Bilayer Models for Duchenne Cardiomyopathy Modelling and Drug Discovery KU Leuven
Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder characterized by DYSTROPHIN (DYS) deficiency. DYS is a sarcolemmal protein which mainly links the cytoskeleton to the extracellular matrix (ECM), by interacting with the dystrophin glycoprotein complex (DGC). Dilated Cardiomyopathy (DC) represents the major cause of death in late-stage DMD patients. In addition, DMD patients often develop left ventricular ...
It takes two to tango_ a decryption of Marfan cardiomyopathy using human iPSC- derived cardiac cells and engineered heart tissues Ghent University
Marfan syndrome is a systemic disorder caused by defects in fibrillin-1, a matrix protein. Cardiovascular manifestations, particularly in the aorta, are the most life-threatening consequences. Moreover, accumulating evidence indicates that Marfan syndrome is causing a primary cardiomyopathy. Importantly, the cardiac stroma, consisting of cardiac fibroblasts, is increasingly considered to be an active player in heart development, cardiac ...
Gene Therapy for treatment of rare inherited Arrhythmogenic Cardiomyopathy KU Leuven
Development of a cure for rare cardiac diseases is a risky, costly and time-consuming process, which is hampered by insufficient insight into pathophysiological mechanisms of the diseases and lack of relevant disease models.
The GEREMY consortium proposes to overcome this challenge by developing a gene therapy (GT) for inherited arrhythmogenic cardiomyopathy (ACM), by targeting the disease-causing PLN (non-desmosomes) and PKP2 (cardiac ...
CARdiomyopathy in type 2 DIAbetes mellitus KU Leuven
A rapidly evolving epidemic in Type 2 Diabetes (T2DM) is afflicting all ages, sexes and socioeconomic classes which includes serious comorbidities such as heart diseases. While ischaemic heart disease represents the major cause of death of T2DM patients, heart failure (80% of Heart Failure with preserved Ejection Fraction) is the second most common cardiovascular disease in T2DM patients. The aim of CARDIATEAM is to determine whether T2DM ...
Stakeholder Perspectives on Gene Therapy in Cardiomyopathy KU Leuven
Project Arrhythmogenic cardiomyopathy (ACM) is a condition affecting the myocardium, the heart’s muscle wall. A defect in proteins that connect heart muscle cells (myocytes) leads to the death of these cells, which are then replaced by scar tissue and fat cells. As a result, the heart muscle weakens and struggles to pump sufficient oxygen-rich blood to the rest of the body. Over time, ACM can lead to arrhythmias, heart failure, and sudden ...
Exploring molecular mechanisms underlying arrhythmogenic cardiomyopathy using human engineered heart tissue Ghent University
Study of the cellular and molecular mechanisms underlying cardiomyopathy caused by transcription factor PR domain containing 16 (Prdm16) deficiency in cardiomyocytes and non-cardiomyocyte cell types KU Leuven
Cardiomyopathies (CMs) are diseases of the heart with a heterogeneous origin. Despite this diversity, all CMs are treated with general symptom-relieving drugs. No curative treatments targeting the underlying disease mechanisms are available likely due to the lack of specific mechanistic knowledge for each CM subtype. In this project, we intend to use cutting edge (epi)genetic tools to resolve the cellular and molecular mechanisms that cause ...
The effects of titin-truncating variants on metabolism and a possible target for intervention for dilated cardiomyopathy KU Leuven
Dilated cardiomyopathy (DCM) has a strong genetic basis, of which truncating variants in titin (TTNtv) are the most prevalent. However, a disease penetrance with reduced expression has been suggested. It seems that TTNtv carriers can cope with the molecular consequences of the variant and prevent full disease expression, until an additional trigger is introduced. Evidence is accumulating that the metabolic adaptation and observed ...