A5081073903- CRISPR and Genetic Engineering
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Receptor Mechanisms and Signaling
- Pluripotent Stem Cells Research
- Neuroscience and Neural Engineering
- Gastroesophageal reflux and treatments
- Helicobacter pylori-related gastroenterology studies
- RNA regulation and disease
- Nanoplatforms for cancer theranostics
- Chromosomal and Genetic Variations
- Neonatal Respiratory Health Research
- RNA Interference and Gene Delivery
- Cancer, Stress, Anesthesia, and Immune Response
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- bioluminescence and chemiluminescence research
- Peripheral Nerve Disorders
- Nuclear Structure and Function
- Eosinophilic Esophagitis
- Amyotrophic Lateral Sclerosis Research
- Cancer-related gene regulation
- Advanced Fluorescence Microscopy Techniques
- Photochromic and Fluorescence Chemistry
- Cancer Research and Treatments
MRC Toxicology Unit
2024
University of Cambridge
2024
University of Nottingham
2009-2023
Sechenov University
2015-2018
University of Glasgow
2006
University of Münster
2002-2005
Institute of Cytology
2001
Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic opened a new era safety pharmacology. Nevertheless, predictive using hPSC-CMs contrasts almost total success. Since this likely relates...
UVB-induced lesions in mammalian cellular DNA can, through the process of mutagenesis, lead to carcinogenesis. However, eukaryotic cells have evolved complex mechanisms genomic surveillance and damage repair counteract effects UVB radiation. We show that following damage, there is an overall inhibition protein synthesis translational reprogramming. This reprogramming allows selective DDR proteins, such as ERCC1, ERCC5, DDB1, XPA, XPD, OGG1 relies on upstream ORFs 5′ untranslated region these...
Cordycepin (3′ deoxyadenosine) has long been used in the study of vitro assembled polyadenylation complexes, because it terminates poly(A) tail and arrests cleavage complex. It is derived from caterpillar fungi, which are highly prized Chinese traditional medicine. Here we show that cordycepin specifically inhibits induction inflammatory mRNAs by cytokines human airway smooth muscle cells without affecting expression control mRNAs. treatment results shorter tails, a reduction efficiency mRNA...
We show that a common polymorphic variant in the ERCC5 5′ untranslated region (UTR) generates an upstream ORF (uORF) affects both background expression of this protein and its ability to be synthesized following exposure agents cause bulky adduct DNA damage. Individuals harbor uORF1 have marked resistance platinum-based agents, illustrated by significantly reduced progression-free survival pediatric ependymoma patients treated with such compounds. Importantly, inhibition DNA-PKcs restores...
The therapeutic action of a drug depends on its ability to engage with molecular target in vivo. However, current discovery strategies quantify levels within organs rather than determining the binding drugs directly their specific targets This is particular problem for assessing potential that malignant tumors where access and may be impaired by disrupted vasculature local hypoxia. Here we have used triple-negative human breast cancer cells expressing β2-adrenoceptors tagged bioluminescence...
Vascular endothelial growth factor (VEGF) is an important mediator of cell proliferation and angiogenesis via its receptor VEGFR2. A common tumor associated with elevated VEGFR2 signaling infantile hemangioma that caused by a rapid vascular cells. The current first-line treatment for the β-adrenoceptor antagonist, propranolol, although mechanism action not understood. Here we have used bioluminescence resonance energy transfer genetically tagged NanoLuc luciferase to demonstrate oligomeric...
CUGBP, Elav-like family member 1 (CELF1) is an RNA binding protein with important roles in the regulation of splicing, mRNA decay and translation. CELF1 contains three recognition motifs (RRMs). We used gel retardation, filtration, isothermal titration calorimetry NMR studies to investigate by first two RRMs CELF1. shows that RRM1 promiscuous both UGU CUG repeat sequences comparable chemical shift perturbations. In contrast, RRM2 greater selectivity for UGUU rather than motifs. A construct...
Modeling disease with human pluripotent stem cells (hPSCs) is hindered because the impact on cell phenotype from genetic variability between individuals can be greater than pathogenic mutation. While "footprint-free" Cas9/CRISPR editing solves this issue, existing approaches are inefficient or lengthy. In study, a simplified PiggyBac strategy shortened hPSC by 2 weeks and required one round of clonal expansion genotyping rather two, similar efficiencies to longer conventional process....
Anatomy of the conduction tracts cerebral cortex has been studied for a long time. Invention diffusion tensor tractography renewed interest in this subject. The objectives work were to develop and improve protocols dissection association human brain with studying features their segmentation, topography, variability, compare obtained data MR data, prepare further clinical anatomical studies.We used 18 hemispheres (from 10 males 8 females; 9 left right hemispheres). mean age cadavers was 68...
Abstract The importance of cell phenotype in determining the molecular mechanisms underlying β 2 ‐adrenoceptor (β2AR) function has been noted previously when comparing responses primary cells and recombinant model lines. Here, we have generated haplotype‐specific SNAP‐tagged β2AR human embryonic stem (ES) lines applied fluorescence correlation spectroscopy (FCS) to study surface receptors progenitor differentiated fibroblasts cardiomyocytes. FCS was able quantify number diffusion both...
The median overall survival of glioblastoma patients is about 15 months. Only a small number survive 3 years. factors favorable prognosis for the 'longevity phenomenon' in are not fully understood.to determine occurrence rate long-living with glioblastomas, identify clinical predictors prognosis, and presence prognostic significance an IDH1 mutation.Among 1494 operated on at Burdenko Neurosurgical Institute from 2007 to 2012, there were 84 (5.6%) who lived more than years after primary...
Abstract Chromatin of male and female gametes undergoes a number reprogramming events during the transition from germ cell to embryonic developmental programs. Although rearrangement DNA methylation patterns occurring in zygote has been extensively characterized, little is known about dynamics modifications spermatid maturation. Here, we demonstrate that 5-carboxylcytosine (5caC) correlate with active transcription LINE-1 retroelements murine spermiogenesis. We show open reading frames...
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The results of a clinical study showing the importance surfactant proteins A and D in assessing activity progression idiopathic pulmonary fibrosis chronic lung sarcoidosis are presented. Aim. To significance SP-A, SP-D sarcoidosis. We examined 81 patients with morphologically confirmed diagnoses (ILF) sarcoidosis, control group 20 healthy individuals. MSCT thoracic organs chest was performed, diffusivity lungs examined, oxygen saturation determined. In serum, SP-A were determined by...
During normal- and patho-physiological situations, the behavior of beta2-adrenoreceptor (β2AR) is influenced by polymorphic variants. The functional impact such polymorphisms has been suggested from data derived genetic association studies, in vitro experiments with primary cells, transgenic overexpression models. However, heterogeneous background non-physiological transgene expression levels confound interpretation, leading to conflicting mechanistic conclusions. To overcome these...