A5071937290- Epigenetics and DNA Methylation
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- Acute Lymphoblastic Leukemia research
- Hemoglobinopathies and Related Disorders
- CRISPR and Genetic Engineering
- Metabolism and Genetic Disorders
- Protein Degradation and Inhibitors
- Erythropoietin and Anemia Treatment
- Antimicrobial Resistance in Staphylococcus
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Renal and related cancers
- Kruppel-like factors research
- Cytokine Signaling Pathways and Interactions
- Toxin Mechanisms and Immunotoxins
- Biochemical and Structural Characterization
- Immune Response and Inflammation
- RNA regulation and disease
- MicroRNA in disease regulation
- Cancer Cells and Metastasis
- Erythrocyte Function and Pathophysiology
University Hospital of Basel
2016-2024
University of Basel
2016-2024
Research Institute of Molecular Pathology
2022-2024
Vienna Biocenter
2018-2023
Medical University of Vienna
2023
Boehringer Ingelheim (Austria)
2023
Nabriva Therapeutics (Austria)
2023
Slovak Academy of Sciences
2014
Abstract Epigenetic gene regulation and metabolism are highly intertwined, yet little is known about whether altered epigenetics influence cellular during cancer progression. Here, we show that EZH2 NRASG12D mutations cooperatively induce progression of myeloproliferative neoplasms to penetrant, transplantable, lethal myeloid leukemias in mice. EZH1, an homolog, indispensable for EZH2-deficient leukemia-initiating cells constitutes epigenetic vulnerability. BCAT1, which catalyzes the...
Staphylococcus aureus is a major human pathogen associated with high mortality. The emergence of antibiotic resistance and the inability antibiotics to counteract bacterial cytotoxins involved in pathogenesis S. call for novel therapeutic approaches, such as passive immunization monoclonal antibodies (mAbs). complexity staphylococcal past failures single mAb products represent considerable barriers antibody-based therapeutics. Over few years, efforts have focused on neutralizing α-hemolysin....
Myeloproliferative neoplasm (MPN) patients frequently show co-occurrence of JAK2-V617F and mutations in epigenetic regulator genes, including EZH2. In this study, we that loss Ezh2 hematopoietic cells contribute synergistically to the development MPN. The MPN phenotype induced by was accentuated JAK2-V617F;Ezh2−/− mice, resulting very high platelet neutrophil counts, more advanced myelofibrosis, reduced survival. These mice also displayed expansion stem cell progenitor compartments a shift...
Familial erythrocytosis with elevated erythropoietin levels is frequently caused by mutations in genes that regulate oxygen-dependent transcription of the gene encoding ( EPO). We identified a mutation EPO cosegregated disease logarithm odds (LOD) score 3.3 family autosomal dominant erythrocytosis. This mutation, single-nucleotide deletion (c.32delG), introduces frameshift exon 2 interrupts translation main messenger RNA (mRNA) transcript but initiates excess production from what normally...
ABSTRACT The Escherichia coli sequence type 131 (ST131)-O25b:H4 clone has spread worldwide and become responsible for a significant proportion of multidrug-resistant extraintestinal infections. We generated humanized monoclonal antibodies (MAbs) that target the lipopolysaccharide O25b antigen conserved within this lineage. These MAbs bound to surface live bacterial cells irrespective capsular expressed. In serum bactericidal assay in vitro , induced >95% killing presence human as...
Janus kinase 2 (JAK2) plays a critical role in orchestrating hematopoiesis, and its deregulation leads to various blood disorders, most importantly myeloproliferative neoplasms (MPNs). Ruxolitinib, fedratinib, momelotinib, pacritinib are FDA-/EMA-approved JAK inhibitors effective relieving symptoms MPN patients but show variable clinical profiles due poor selectivity. The development of next-generation JAK2 is hampered by the lack comparative functional analysis knowledge molecular basis...
Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient inducible suppression of any gene upon introduction a synthetic target sequence into non-coding transcript regions. ARTi establishes scalable loss-of-function tool with full control over
Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient inducible suppression of any gene upon introduction a synthetic target sequence into non-coding transcript regions. ARTi establishes scalable loss-of-function tool with full control over
Host defense against Staphylococcus aureus greatly depends on bacterial clearance by phagocytic cells. LukGH (or LukAB) is the most potent staphylococcal leukocidin towards human phagocytes in vitro, but its role pathogenesis obscured lack of suitable small animal models because has limited or no cytotoxicity rodent and rabbit compared with polymorphonuclear cells (PMNs) likely due to an impaired interaction cellular receptor, CD11b. We aimed at adapting for host improving binding homolog...
Abstract The vertebrate transcription factor SOX2 (SRY Homology Box 2) is essential for stem cell maintenance, a prominent (co)inductor of pluripotency in reprogramming technology, and an oncogenic driver transformation, therapy resistance, disease relapse cancer. These fate discriminatory events are currently understood as SOX2-imposed changes DNA activity the resultant co-transcriptional rewiring inside cell’s nucleus. Cytoplasmic forms SOX2, on other hand, receive comparatively little...
Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient, inducible, reversible suppression of any gene upon introduction a synthetic target sequence into non-coding transcript regions. ARTi establishes scalable loss-of-function tool with full control over
<p>Table S2 shows differentially expressed genes by RNA-seq</p>
<p>Table S4 shows key reagents and resources</p>
<p>Table S1 shows the list of genomic datasets</p>
<p>Table S5 shows transitions and parameters used for LC-MS</p>
<div>Abstract<p>Epigenetic gene regulation and metabolism are highly intertwined, yet little is known about whether altered epigenetics influence cellular during cancer progression. Here, we show that EZH2 NRAS<sup>G12D</sup> mutations cooperatively induce progression of myeloproliferative neoplasms to penetrant, transplantable, lethal myeloid leukemias in mice. EZH1, an homolog, indispensable for EZH2-deficient leukemia-initiating cells constitutes epigenetic...
<p>Supplementary Figures and Legends combined file contains 14 supplementary figures</p>
<p>Table S1 shows the list of genomic datasets</p>
<p>Table S3 shows sequences of primers and shRNAs</p>