Publications by authors named "Lieve E van der Maarel"
The electrical impulses that coordinate the sequential, rhythmic contractions of the atria and ventricles are initiated and tightly regulated by the specialized tissues of the cardiac conduction system. In the mature heart, these impulses are generated by the pacemaker cardiomyocytes of the sinoatrial node, propagated through the atria to the atrioventricular node where they are delayed and then rapidly propagated to the atrioventricular bundle, right and left bundle branches, and finally, the peripheral ventricular conduction system. Each of these specialized components arise by complex patterning events during embryonic development.
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- - The study investigates the role of 3D chromatin organization in gene regulation and its link to human Mendelian diseases, particularly focusing on a new cardiac condition found in 7 families caused by a deletion of CTCF binding sites on chromosome 4q25.
- - This deletion results in the fusion of topologically associating domains (TADs) and alters chromatin structure, affecting the expression of the PITX2 gene, which is critical for heart function.
- - Using a mouse model that mimics the human genetic deletion, researchers observed changes in PITX2 expression in the heart, leading to the conclusion that TAD remodeling due to CTCF site deletion is responsible for a novel autosomal dominant Mend
The sinoatrial node (SAN) is the primary pacemaker of the mammalian heart, initiating its electrical activation and ensuring that the heart's functional cardiac output meets physiological demand. SAN dysfunction (SND) can cause complex cardiac arrhythmias that can manifest as severe sinus bradycardia, sinus arrest, chronotropic incompetence and increased susceptibility to atrial fibrillation, among other cardiac conditions. SND has a complex aetiology, with both pre-existing disease and heritable genetic variation predisposing individuals to this pathology.
View Article and Find Full Text PDFT-cell products derived from third-party donors are clinically applied, but harbor the risk of off-target toxicity induction of allo-HLA cross-reactivity directed against mismatched alleles. We used third-party donor-derived virus-specific T cells as model to investigate whether virus-specificity, HLA restriction and/or HLA background can predict the risk of allo-HLA cross-reactivity. Virus-specific CD8 T cells were isolated from HLA-A01:01/B08:01 or HLA-A02:01/B07:02 positive donors.
View Article and Find Full Text PDFBackground: Adoptive transfer of genetically engineered T cells expressing antigen-specific T-cell receptors (TCRs) is an appealing therapeutic approach for Epstein-Barr virus (EBV)-associated malignancies of latency type II/III that express EBV antigens (LMP1/2). Patients who are HLA-A*01:01 positive could benefit from such products, since no T cells recognizing any EBV-derived peptide in this common HLA allele have been found thus far.
Methods: HLA-A*01:01-restricted EBV-LMP2-specific T cells were isolated using peptide major histocompatibility complex (pMHC) tetramers.