A5040318856- RNA Research and Splicing
- MicroRNA in disease regulation
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Atherosclerosis and Cardiovascular Diseases
- RNA Interference and Gene Delivery
- Circular RNAs in diseases
- Phagocytosis and Immune Regulation
- Genomics and Phylogenetic Studies
- Single-cell and spatial transcriptomics
- Platelet Disorders and Treatments
- 3D Printing in Biomedical Research
- Immune Cell Function and Interaction
- Extracellular vesicles in disease
- Advanced biosensing and bioanalysis techniques
- Plant Molecular Biology Research
- Chromosomal and Genetic Variations
- Tryptophan and brain disorders
- Circadian rhythm and melatonin
- Cardiac Fibrosis and Remodeling
- Physiological and biochemical adaptations
- Cancer-related Molecular Pathways
- Renal Diseases and Glomerulopathies
- Angiogenesis and VEGF in Cancer
German Centre for Cardiovascular Research
2018-2024
Technical University of Munich
2018-2023
Institute of Pharmacology
2022
Digital Research Alliance of Canada
2022
Heartland Alliance
2022
University of Regensburg
2011-2016
Hospital de Clínicas "José de San Martín"
2015
University of Buenos Aires
2015
University of Groningen
2012
University Medical Center Groningen
2012
Background: Long noncoding RNAs have emerged as critical molecular regulators in various biological processes and diseases. Here we sought to identify functionally characterize long potential mediators abdominal aortic aneurysm development. Methods: We profiled RNA transcript expression 2 murine models, Angiotensin II (ANGII) infusion apolipoprotein E–deficient ( ApoE −/− ) mice (n=8) porcine pancreatic elastase instillation C57BL/6 wild-type (n=12). The H19 was identified 1 of the most...
Cardiac macrophages (cMPs) are increasingly recognized as important regulators of myocardial homeostasis and disease, yet the role noncoding RNA in these cells is largely unknown. Small sequencing entire miRNomes major cardiac cell fractions revealed microRNA-21 (miR-21) single highest expressed microRNA cMPs, both health disease (25% 43% all reads, respectively). MiR-21 has been previously reported a key driving tissue fibrosis. Here, we aimed to determine function macrophage miR-21 on...
Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity mortality. Short-term immobility-related conditions are risk factor for the development VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears paralyzed spinal cord injury (SCI) patients protected from We aimed to identify mechanisms immobility-associated VTE protection in cross-species approach. Mass spectrometry-based proteomics revealed an...
Disruption of the physiologic sleep-wake cycle and low melatonin levels frequently accompany cardiac disease, yet underlying mechanism has remained enigmatic. Immunostaining sympathetic axons in optically cleared pineal glands from humans mice with disease revealed their substantial denervation compared controls. Spatial, single-cell, nuclear, bulk RNA sequencing traced this defect back to superior cervical ganglia (SCG), which responded accumulation inflammatory macrophages, fibrosis,...
MicroRNAs (miRNAs) are small noncoding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located the 3′-untranslated region (3′-UTR) of mRNAs leading translational repression deadenylation-induced mRNA degradation. Most processed from hairpin-structured precursors by consecutive action RNase III enzymes Drosha Dicer. However, processing miR-451 is Dicer independent cleavage mediated endonuclease Ago2....
miR-21 is a central regulator of cardiac fibrosis, and its inhibition in small-animal models has been shown to be an effective antifibrotic strategy various organs, including the heart. Effective delivery therapeutic antisense micro–ribonucleic acid (antimiR) molecules myocardium larger organisms challenging, though, remains established for chronic heart failure. The aims this study were test applicability efficacy local, catheter-based antimiR-21 pig model failure determine effect on...
Renal ischemia-reperfusion (I/R) injury is a major cause of AKI. Noncoding RNAs are intricately involved in the pathophysiology this form Transcription hypoxia-induced, long noncoding RNA H19, which shows high embryonic expression and silenced adults, upregulated renal I/R injury.Lentivirus-mediated overexpression, as well antisense oligonucleotide-based silencing, modulated H19 vitro. In vivo analyses used constitutive knockout mice. addition, vein injection adeno-associated virus 2 (AAV2)...
MicroRNAs (miRNAs) are short regulatory RNAs derived from longer precursor RNAs. miRNA biogenesis has been studied in animals and plants, recently elucidating more complex aspects, such as non-conserved, species-specific, heterogeneous populations. Small RNA sequencing data can help computationally identifying genomic loci of precursors. The challenge is to predict a valid inhomogeneous read coverage library: while the mature typically produces many sequence reads, remaining part covered...
We determined the effect of p53 activation on de novo protein synthesis using quantitative proteomics (pulsed stable isotope labeling with amino acids in cell culture/pSILAC) colorectal cancer line SW480. This was combined mRNA and noncoding RNA expression analyses by next generation sequencing (RNA-, miR-Seq). Furthermore, genome-wide DNA binding analyzed chromatin-immunoprecipitation (ChIP-Seq). Thereby, we identified differentially regulated proteins (542 up, 569 down), mRNAs (1258 415...
Abstract Platelet homeostasis is essential for vascular integrity and immune defence 1,2 . Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, cellular molecular mechanisms required to constantly replenish pool MKs their progenitor cells (megakaryopoiesis) remains unclear 3,4 Here we use intravital imaging track dynamics megakaryopoiesis over days. We identify plasmacytoid dendritic (pDCs) as homeostatic sensors that...
The Epstein-Barr virus (EBV) is an oncogenic human Herpes involved in the pathogenesis of nasal NK/T-cell lymphoma. EBV encodes microRNAs (miRNAs) and induces changes host cellular miRNA profile. MiRNAs are short non-coding RNAs about 19–25 nt length that regulate gene expression by post-transcriptional mechanisms frequently deregulated malignancies including cancer. microRNA profiles EBV-positive lymphoma, non-infected T-cell lymphoma normal thymus were established deep sequencing small RNA...
Argonaute (Ago) proteins form the core of RNA-induced silencing complexes (RISCs) and mediate small RNA-guided gene silencing. In RNAi, short interfering RNAs (siRNAs) guide RISCs to complementary target RNAs, leading cleavage by endonuclease Ago2. Noncatalytic Ago proteins, however, contribute RNAi as well but cannot cleave RNA often generate off-target effects. Here we show that synthetic siRNA duplexes interact with all a functional RISC rapidly assembles only around By stabilizing...
In this study, organ-on-chip technology is used to develop an in vitro model of medium-to-large size arteries, the artery-on-a-chip (AoC), with objective recapitulate structure arterial wall and relevant hemodynamic forces affecting luminal cells. AoCs exposed either vivo-like shear stress values or kept static conditions are assessed generate a panel novel genes modulated by stress. Considering crucial role played alterations carotid arteries affected atherosclerosis (CAD) abdominal aortic...
To secure the functionality of activated macrophages in innate immune response, efficient life span control is required. Recognition bacterial lipopolysaccharides (LPS) by toll-like receptor 4 (TLR4) induces downstream signaling pathways, which merge to induce expression cytokine genes and anti-apoptotic genes. MicroRNAs (miRNAs) have emerged as important inflammatory response modulators, but information about their functional impact on apoptosis scarce. identify miRNAs differentially...
Abstract Abnormalities of ventricular action potential cause malignant cardiac arrhythmias and sudden death. Here, we aim to identify microRNAs that regulate the human ask whether their manipulation allows for therapeutic modulation abnormalities. Quantitative analysis microRNA targetomes in myocytes identifies miR-365 as a primary repolarizing ion channels. Action recordings patient-specific induced pluripotent stem cell-derived show elevation significantly prolongs duration derived from...
MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in many cellular pathways. MiRNAs associate with members of the Argonaute protein family and bind to partially complementary sequences on mRNAs induce translational repression or mRNA decay. Using deep sequencing Northern blotting, we characterized miRNA expression wild type miR‐155‐deficient dendritic cells (DCs) macrophages. Analysis different stimuli (LPS, LDL, eLDL, oxLDL) reveals a direct influence miR‐155 levels...
Abstract RNA.DNA:DNA triple helix (triplex) formation is a form of RNA–DNA interaction which regulates gene expression but difficult to study experimentally in vivo. This makes accurate computational prediction such interactions highly important the field RNA research. Current predictive methods use canonical Hoogsteen base pairing rules, whilst biophysically valid, may not reflect plastic nature cell biology. Here, we present first optimization approach learn probabilistic model describing...
The highly conserved, multifunctional YB-1 is a powerful breast cancer prognostic indicator. We report on pervasive role for in which it associates with thousands of nonpolyadenylated short RNAs (shyRNAs) that are further processed into small (smyRNAs). Many these have previously been identified as functional noncoding (http://www.johnlab.org/YB1). novel, abundant, 3′-modified RNA antisense to Dicer1 (Shad1) colocalizes P-bodies and stress granules. expression Shad1 was shown correlate whose...
Volvox carteri (V. carteri) is a multicellular green alga used as model system for the evolution of multicellularity. So far, contribution small RNA pathways to these phenomena not understood. Thus, we have sequenced V. Argonaute 3 (VcAGO3)-associated RNAs from different developmental stages. Using this functional approach, define microRNA (miRNA) repertoire and show that miRNAs are conserved in closely related unicellular Chlamydomonas reinhardtii. Furthermore, find differentially expressed...
Obesity is accompanied by chronic inflammation of VAT, which promotes metabolic changes, and purinergic signaling has a key role in wide range inflammatory diseases. Therefore, we addressed whether fat could be differentially modulated this pathway the MUO individuals who remain MHO. Our results show that necrotized VAT both groups released greater levels ATP compared with lean donors. Interestingly, tissue SVCs showed up-regulation engagement P2X7R. The extracellular concentration regulated...