A5083528942- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- DNA Repair Mechanisms
- Congenital Heart Disease Studies
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- Cardiovascular and Diving-Related Complications
- Cardiac Structural Anomalies and Repair
- Immune responses and vaccinations
- HIV Research and Treatment
- Genetic Syndromes and Imprinting
- Cardiovascular Issues in Pregnancy
- Natural Language Processing Techniques
- Immune cells in cancer
- RNA Research and Splicing
- Cardiac electrophysiology and arrhythmias
- Retirement, Disability, and Employment
- melanin and skin pigmentation
- Single-cell and spatial transcriptomics
- Advanced biosensing and bioanalysis techniques
- MicroRNA in disease regulation
- Genomic variations and chromosomal abnormalities
University of Oxford
2015-2025
University of California, Davis
2022-2024
Ludwig Cancer Research
2016-2024
Na Homolce Hospital
2015-2022
Charles University
2015
Interface (United Kingdom)
2015
Abstract The quality of human translation was long thought to be unattainable for computer systems. In this study, we present a deep-learning system, CUBBITT, which challenges view. context-aware blind evaluation by judges, CUBBITT significantly outperformed professional-agency English-to-Czech news in preserving text meaning (translation adequacy). While is still rated as more fluent, shown substantially fluent than previous state-of-the-art Moreover, most participants Translation Turing...
DNA replication plays an important role in mutagenesis, yet little is known about how it interacts with other mutagenic processes. Here, we use somatic mutation signatures-each representing a process-derived from 3056 patients spanning 19 cancer types to quantify the strand asymmetry of mutational signatures around origins and between early late replicating regions.
Abstract Precision epigenome editing has gained significant attention as a method to modulate gene expression without altering genetic information. However, major limiting factor been that the changes are often transient, unlike life-long epigenetic occur frequently in nature. Here, we systematically interrogate ability of CRISPR/dCas9-based editors (Epi-dCas9) engineer persistent silencing. We elucidated cis regulatory features contribute differential stability reprogramming, such active...
For inoperable esophageal adenocarcinoma (EAC), identifying patients likely to benefit from recently approved immunochemotherapy (ICI+CTX) treatments remains a key challenge. We address this using uniquely designed window-of-opportunity trial (LUD2015-005), in which 35 EAC received first-line immune checkpoint inhibitors for four weeks (ICI-4W), followed by ICI+CTX. Comprehensive biomarker profiling, including generation of 65,000-cell single-cell RNA-sequencing atlas cancer, as well...
Abstract Promoter DNA methylation is a key epigenetic mark, commonly associated with gene silencing. However, we noticed that positive association between promoter and expression surprisingly common in cancer. Here, use hit-and-run CRISPR/dCas9 epigenome editing to evaluate how deposition of can regulate dependent on pre-existing chromatin environment. While the predominant effect non-bivalent promoters repression, show bivalent this often leads activation. We demonstrate gain reduced MTF2...
Cardiovascular disease is the leading cause of death, demanding new tools to improve mechanistic understanding and overcome limitations stem cell animal-based research. We introduce T-World, a highly general virtual model human ventricular cardiomyocyte suitable for multiscale studies. T-World shows comprehensive agreement with physiology, from electrical activation contraction, first replicate all key cellular mechanisms driving life-threatening arrhythmias. Extensively validated on unseen...
Natriuretic peptides are often elevated in congenital heart disease (CHD); however, the clinical impact on mortality is unclear. The aim of our study was to evaluate prognostic value N-terminal pro-brain natriuretic peptide (NT-proBNP) prediction all-cause adults with different CHD. In this prospective longitudinal study, we evaluated NT-proBNP 1,242 blood samples from 646 outpatient stable CHD (mean age 35 ± 12 years; 345 women). Patients were followed up for 6 3 (1 10) years. rate 5% (35...
CpG dinucleotides are the main mutational hot-spot in most cancers. The characteristic elevated C>T mutation rate sites has been related to 5-methylcytosine (5mC), an epigenetically modified base which resides CpGs and plays a role transcription silencing. In brain nearly third of 5mCs have recently found exist form 5-hydroxymethylcytosine (5hmC), yet effect 5hmC on processes is still poorly understood. Here we show that associated with up 53% decrease frequency mutations context compared...
Background: Cardiac alternans is an important precursor to arrhythmia, facilitating formation of conduction block, and re-entry. Diseased hearts were observed be particularly vulnerable alternans, mainly in heart failure or after myocardial infarction. Alternans typically linked oscillation calcium cycling, the sarcoplasmic reticulum (SR). While role SR reuptake well established, altered release by ryanodine receptors has not yet been studied extensively. At same time, there strong evidence...
Background: Following myocardial infarction (MI), the myocardium is prone to calcium-driven alternans, which typically precedes ventricular tachycardia and fibrillation. MI also associated with remodeling of sympathetic innervation in infarct border zone, although how this influences arrhythmogenesis controversial. We hypothesize that zone most vulnerable β-adrenergic receptor stimulation can suppresses this, investigate consequences terms arrhythmogenic mechanisms. Methods Results: Anterior...
Abstract Human cell line models, including the neuronal precursor LUHMES, are important for investigating developmental transcriptional dynamics within imprinted regions, particularly 15q11-q13 Angelman (AS) and Prader-Willi (PWS) syndrome locus. AS results from loss of maternal UBE3A in neurons, where paternal allele is silenced by a convergent antisense transcript UBE3A-ATS, lncRNA that terminates at PWAR1 non-neurons. qRT-PCR analysis confirmed exclusive progressive increase UBE3A-ATS...
Objective The patients after Mustard and Senning corrections of transposition the great arteries (TGA) are at an increased risk unexpected death. aim this study was to identify markers allowing stratification atrial switch correction TGA provide them with optimum care. Methods Results In study, 87 were retrospectively evaluated followed-up between 2005 2015. mortality during follow-up 9% (8 cardiac deaths). Markers significantly predictive death using univariable Cox proportional hazard...
Since genome instability can drive cancer initiation and progression, cells have evolved highly effective ubiquitous DNA damage response (DDR) programs. However, some (for example, in skin) are normally exposed to high levels of DNA-damaging agents. Whether such high-risk possess lineage-specific mechanisms that tailor repair the tissue remains largely unknown. Using melanoma as a model, we show here microphthalmia-associated transcription factor MITF, lineage addition oncogene coordinates...
C-to-T transitions in CpG dinucleotides are the most prevalent mutations human cancers and genetic diseases. These have been attributed to deamination of 5-methylcytosine (5mC), an epigenetic modification found on CpGs. We recently linked CpG>TpG replication hypothesized that errors introduced by polymerase ε (Pol ε) may represent alternative source mutations. Here we present a new method called error rate sequencing (PER-seq) measure spectrum DNA polymerases isolation. find common...
Atrial septal defect (ASD) is the most common congenital heart disease (CHD) in adults and pulmonary hypertension (PH) an established risk factor. A decision whether to perform ASD closure, especially elderly patients with PH, a complex dilemma. The aim of our study was compare long-term survival closed open ASD.A retrospective cohort performed on 427 (median age at diagnosis 38 years, IQR 18-56) out which 186 (44%) manifested PH. closure PH only considered without Eisenmenger syndrome...
Since genome instability can drive cancer initiation and progression, cells have evolved highly effective ubiquitous DNA Damage Response (DDR) programs. However, some cells, in skin for example, are normally exposed to high levels of damaging agents. Whether such high-risk possess lineage-specific mechanisms that tailor repair the tissue remains largely unknown. Here we show, using melanoma as a model, microphthalmia-associated transcription factor MITF, lineage addition oncogene coordinates...
ABSTRACT DNA replication plays an important role in mutagenesis, yet little is known about how it interacts with other mutagenic processes. Here, we use somatic mutation signatures – each representing a process derived from 3056 patients spanning 19 cancer types to quantify the asymmetry of mutational around origins and between early late replicating regions. We observe that 22 out 29 are significantly impacted by replication. The distinct associations different timing direction shed new...