A5002034203- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- RNA Research and Splicing
- Protist diversity and phylogeny
- Estrogen and related hormone effects
- Parasitic Infections and Diagnostics
- Reproductive Biology and Fertility
- Pharmacogenetics and Drug Metabolism
- Cystic Fibrosis Research Advances
- Bacterial biofilms and quorum sensing
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- Prostate Cancer Treatment and Research
- TGF-β signaling in diseases
- HIV/AIDS drug development and treatment
- Endoplasmic Reticulum Stress and Disease
- Methane Hydrates and Related Phenomena
- Cancer-related molecular mechanisms research
- Advanced biosensing and bioanalysis techniques
- Inflammatory mediators and NSAID effects
- Pneumonia and Respiratory Infections
- Breast Cancer Treatment Studies
- Lung Cancer Treatments and Mutations
- Antibiotic Resistance in Bacteria
University of Copenhagen
2008-2025
Business Innovation Centre
2021
Rigshospitalet
2013
Copenhagen University Hospital
2012-2013
University of California, Berkeley
2011
University of Oxford
1988
Impairment of translation can lead to collisions ribosomes, which constitute an activation platform for several ribosomal stress-surveillance pathways. Among these is the ribotoxic stress response (RSR), where sensing by MAP3K ZAKα leads p38 and JNK kinases. Despite insights, physiological ramifications impairment downstream RSR signaling remain elusive. Here, we show that stalling ribosomes sufficient activate ZAKα. In amino acid deprivation full nutrient starvation, impacts on ensuing...
In mammals, members of the transforming growth factor-beta (TGF-β) superfamily are known to have key roles in regulation follicular and development. The aim study was evaluate expression TGF-β factors, their receptors, downstream SMAD signalling molecules TGF-β/bone morphogenetic protein (BMP) antagonists during early human folliculogenesis. Human pre-antral follicles were enzymatically isolated from surplus ovarian tissue obtained women having cortical frozen for fertility preservation. A...
RNase T2 enzymes are produced by a wide range of organisms and have been implicated to function in diverse cellular processes, including stress-induced anticodon loop cleavage mature tRNAs generate tRNA halves. Here we describe family eight genes (RNT2A-RNT2H) the ciliate Tetrahymena thermophila. We constructed strains lacking individual or combinations these RNT2 that were viable but had distinct molecular phenotypes. In only one Rnt2 protein subfamily three catalytically inactive proteins,...
Twenty new compounds, targeting CYP17A1, were synthesized, based on our previous work a benzimidazole scaffold, and their biological activity evaluated. Inhibition of CYP17A1 is an important modality in the treatment prostate cancer, which remains most abundant cancer type men. The assessment included hydroxylase lyase inhibition, CYP3A4 P450 oxidoreductase (POR) as well antiproliferative PC3 cells. potent compounds selected for further analyses including silico modeling. This combined...
Pseudomonas aeruginosa colonizes the cystic fibrosis (CF) airways causing chronic bacterial lung infections. CF patients are routinely treated with macrolides, however, P. is considered insusceptible as consequence of inadequate susceptibility testing leaving resistance mechanism completely overlooked. Here, we investigated a new macrolide caused by ribosomal protein mutations.Investigating longitudinal collection 529 isolates from and analysing 5758 sequences different sources, mutations in...
Ribosomopathies constitute a range of disorders associated with defective protein synthesis mainly affecting hematopoietic stem cells (HSCs) and erythroid development. Here, we demonstrate that deletion poly-pyrimidine-tract-binding 1 (PTBP1) in the compartment leads to development ribosomopathy-like condition. Specifically, loss PTBP1 is decreases HSC self-renewal, differentiation, synthesis. Consistent its function as splicing regulator, deficiency results defects hundreds genes,...
The current study presents the design, synthesis, and evaluation of novel cytochrome P450 17A1 (CYP17A1) ligands. CYP17A1 is a key enzyme in steroidogenic pathway that produces androgens among other steroids, it implicated prostate cancer. obtained compounds are potent inhibitors (sub µM) with antiproliferative activity cancer cell lines. binding mode these also discussed.
Group I introns in nuclear ribosomal RNA of eukaryotic microorganisms are processed by splicing or circularization. The latter results formation full-length circular without ligation the exons and has been proposed to be active intron mobility. We applied qRT-PCR estimate copy number from myxomycete Didymium iridis. In exponentially growing amoebae, found 70 copies per cell. During heat-shock, form is up-regulated more than 500 harbours two ribozymes that have potential linearize circle. To...
The ciliate Tetrahymena thermophila is an important eukaryotic model organism that has been used in pioneering studies of general phenomena, such as ribozymes, telomeres, chromatin structure and genome reorganization. Recent work shown many classes small RNA molecules expressed during vegetative growth or sexual In order to get overview medium-sized (40-500 nt) RNAs from the genome, we created a size-fractionated cDNA library macronuclear analyzed 80 RNAs, most which were previously unknown....
Preantral follicle development is regulated predominantly by factors produced locally within the ovary and itself. In rodents, it well known that transforming growth factor beta (TGF-β) superfamily, including TGF-βs, bone morphogenic proteins (BMPs), differentiation (GDFs), inhibins/activins, follistatin (FST), anti-Müllerian hormone (AMH), one of prominent families via paracrine and/or autocrine mechanisms involved in regulating follicular development. However, full functional significance...
Abstract Ribosomes are complex ribozymes that interpret genetic information by translating messenger RNA (mRNA) into proteins. Natural variation in ribosome composition has been documented several organisms, and can stem from different sources. A key question is whether specific control over heterogeneity represents a mechanism which translation be regulated. We used RiboMeth-seq to demonstrate differential 2’-O-methylation of ribosomal (rRNA) considerable source human cells, modification...
In eukaryotes, 18S, 5.8S, and 28S rRNAs are transcribed as precursor molecules that undergo extensive modification nucleolytic processing to form the mature rRNA species. Central in process small nucleolar RNAs (snoRNAs). The majority of snoRNAs guide site specific chemical modifications but a few involved defining pre-rRNA cleavages. Here, we describe an unusual snoRNA (TtnuCD32) belonging box C/D subgroup from ciliate Tetrahymena thermophila. We show TtnuCD32 is unlikely function it...
Summary Background Cystic fibrosis (CF) patients have reduced mucociliary clearance resulting in recurring and chronic bacterial lung infections. Pseudomonas aeruginosa is one of the most common pathogens to colonize airways CF can persist lungs for decades. infected with P. are treated macrolides inhibit quorum sensing, mucoidity has additional immunomodulatory effects. However, according EUCAST committee, not susceptible leaving resistance mechanisms largely overlooked. Methods Using a...