A5026527049- RNA and protein synthesis mechanisms
- Prostate Cancer Treatment and Research
- RNA Research and Splicing
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Prostate Cancer Diagnosis and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer-related molecular mechanisms research
- Advanced MRI Techniques and Applications
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- Statistical Methods in Clinical Trials
- Cancer, Lipids, and Metabolism
- MicroRNA in disease regulation
- Sperm and Testicular Function
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- Prenatal Screening and Diagnostics
- Advanced Proteomics Techniques and Applications
- Reproductive Biology and Fertility
- Advanced Neuroimaging Techniques and Applications
- Glioma Diagnosis and Treatment
- Thermal Regulation in Medicine
Cancer Research UK
2015-2024
University of Cambridge
2016-2024
École Polytechnique Fédérale de Lausanne
2022-2024
Cancer Research UK Cambridge Center
2016-2019
European Bioinformatics Institute
2018-2019
Epigenomics (Germany)
2013-2016
German Cancer Research Center
2013-2016
Heidelberg University
2013-2016
Medical University of Graz
2013-2015
Dublin City University
2013
Topological domains are key architectural building blocks of chromosomes, but their functional importance and evolutionary dynamics not well defined. We performed comparative high-throughput chromosome conformation capture (Hi-C) in four mammals characterized the conservation divergence chromosomal contact insulation resulting domain architectures within distantly related genomes. show that modular organization chromosomes is robustly conserved syntenic regions this compatible with binding...
Abstract Male gametes are generated through a specialised differentiation pathway involving series of developmental transitions that poorly characterised at the molecular level. Here, we use droplet-based single-cell RNA-Sequencing to profile spermatogenesis in adult animals and multiple stages during juvenile development. By exploiting first wave spermatogenesis, both precisely stage germ cell development enrich for rare somatic cell-types spermatogonia. To capture full complexity including...
Prostate cancer aggressiveness and appropriate therapy are routinely determined following biopsy sampling. Current clinical pathologic parameters insufficient for accurate risk prediction leading primarily to overtreatment also missed opportunities curative therapy.An 8-biomarker proteomic assay intact tissue biopsies predictive of prostate pathology was defined in a study 381 patient with matched prostatectomy specimens. A second blinded 276 cases validated this assay's ability distinguish...
Key challenges of biopsy-based determination prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty risk assessment leads to significant overtreatment, with associated costs morbidity. We developed a performance-based strategy identify protein biomarkers predictive lethality regardless variation. Prostatectomy samples from large patient cohort long follow-up were blindly assessed by expert...
The molecular mechanisms underlying the genesis of cholangiocarcinomas (CCs) are poorly understood. Epigenetic changes such as aberrant hypermethylation and subsequent atypical gene expression characteristic features most human cancers. In CC, data regarding global methylation lacking so far. We performed a genome-wide analysis for promoter in CCs. profiled 10 intrahepatic 8 extrahepatic CCs comparison to non-neoplastic biliary tissue specimens, using methyl-CpG immunoprecipitation (MCIp)...
Mammalian species exhibit a wide range of lifespans. To date, robust and dynamic molecular readout these lifespan differences has not yet been identified. Recent studies have established the existence ageing-associated differentially methylated positions (aDMPs) in human mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesise that aDMPs pan-mammalian variation among different mammalian species. A large-scale integrated analysis six...
Genome stability relies on proper coordination of mitosis and cytokinesis, where dynamic microtubules capture faithfully segregate chromosomes into daughter cells. With a high-content RNAi imaging screen targeting more than 2,000 human lncRNAs, we identify numerous lncRNAs involved in key steps cell division such as chromosome segregation, mitotic duration cytokinesis. Here, provide evidence that the chromatin-associated lncRNA, linc00899, leads to robust delay upon its depletion multiple...
Cholangiocarcinoma (CC) is a rare malignancy of the extrahepatic or intrahepatic biliary tract with an outstanding poor prognosis. Non-surgical therapeutic regimens result in minimally improved survival CC patients. Global genomic analyses identified few recurrently mutated genes, some them genes involved epigenetic patterning. In previous study, we demonstrated global DNA methylation changes CC, indicating major contribution alterations to cholangiocarcinogenesis. Here, aimed at...
Purpose Magnetic resonance relaxation times of most tissues are expected to depend on temperature, which can impact findings in postmortem magnetic imaging or when using for relaxation‐based thermometry. The purpose this study was investigate the exact temperature dependency T 1 , 2 *, and magnetization transfer ratio different structures human brain. Methods To prevent fixation autolysis effects, performed with fresh brain tissues. Following autopsy, coronal slices from five deceased...
The human LINE-1/L1 ORF2 protein is a multifunctional enzyme which plays vital role in the life cycle of L1 retrotransposon. consists an endonuclease domain, followed by central reverse transcriptase domain and carboxy-terminal C-domain with unknown function. Here, we explore nucleic acid binding properties 180-amino segment (CTS) ORF2p vitro. In series experiments involving gel shift assay, demonstrate that CTS binds RNA non-sequence-specific manner. Finally, report mutations destroying...
The assessment of iron content in brain white matter (WM) is high importance for studying neurodegenerative diseases. While R2 * mapping and quantitative susceptibility suitable gray matter, WM still remains an unsolved problem. We propose a new approach mapping, independent diamagnetic contributions myelin by assessing the temperature dependency paramagnetic susceptibility.We used unfixed human slices relaxometry calculated ' as measure microscopic variations at several temperatures...
Abstract Structural variants can contribute to oncogenesis through a variety of mechanisms, yet, despite their importance, the identification structural in cancer genomes remains challenging. Here, we present an integrative framework for comprehensively identifying variation genomes. For first time, apply next-generation optical mapping, high-throughput chromosome conformation capture (Hi-C), and whole genome sequencing systematically detect SVs cells. Using this approach, identify...
Abstract How chronic mutational processes and punctuated bursts of DNA damage drive evolution the cancer genome is poorly understood. Here, we demonstrate a strategy to disentangle quantify distinct mechanisms underlying in single cells, during mitoses at single-strand resolution. To distinguish between (reactive oxygen species (ROS)) acute (ultraviolet light (UV)) mutagenesis, microfluidically separate pairs sister cells from first mitosis following burst UV damage. Strikingly, mutations...
MR relaxation times of most tissues are expected to depend on temperature which can impact findings in post mortem MRI or based thermometry.The purpose this study was investigate the exact dependency T 1 different structures unfixed and fixed human brain samples.Following autopsy, coronal slices from five deceased subjects underwent at 3T a range between 4°C 37°C.T showed linear with highest coefficient cortex (17 ms/°C) lowest white matter (3ms/°C).The fixation tissue lowered additionally...
SUMMARY Understanding male fertility requires an in-depth characterisation of spermatogenesis, the developmental process by which gametes are generated. Spermatogenesis occurs continuously throughout a male’s reproductive window and involves complex sequence steps, both make this difficult to decipher at molecular level. To overcome this, we transcriptionally profiled single cells from multiple distinct stages during first wave where most mature germ cell type is known. This naturally...
Most human aneuploidies originate maternally, due in part to the presence of highly stringent checkpoints during male meiosis. Indeed, sterility is common among aneuploid mice used study chromosomal abnormalities, and germline transmission exogenous DNA has been rarely reported. Here we show that, despite aberrant testis architecture, males Tc1 mouse strain produce viable sperm transmit chromosome 21 create offspring. In these offspring, mapped transcription, transcriptional initiation,...
5090 Background: Current clinical and pathological parameters are insufficient for accurate prediction of progression risk patients with biopsy Gleason grades 3+3 or 3+4. Reasons this include sampling error pathologist grading discordance, resulting in inaccurate prostate pathology assessment. Consequently, a majority these over-treated. We have established novel proteomics-based test, ProMark automated quantitative measurements biomarkers from tumor epithelium intact FFPE tissue. The test...
ABSTRACT Genome stability relies on proper coordination of mitosis and cytokinesis, where dynamic microtubules capture faithfully segregate chromosomes into daughter cells. The role long noncoding RNAs (lncRNAs) in controlling these processes however remains largely unexplored. To identify lncRNAs with mitotic functions, we performed a high-content RNAi imaging screen targeting more than 2,000 human lncRNAs. By investigating major hallmarks cell division such as chromosome segregation,...
Natalizumab is an effective treatment in patients with highly active relapsing-remitting multiple sclerosis (RRMS). However, its positive therapeutic effects have to be weighed against the potential serious adverse event of progressive multifocal leukoencephalopathy (PML). Thus, whenever MS on natalizumab develop uncommon and neurologic symptoms, suspicion PML has raised. The risk becomes higher increasing duration treatment, prior immunosuppressive JC virus (JCV) antibody seropositivity.1...
Abstract Cis- genetic effects are key determinants of transcriptional divergence in discrete tissues and cell types. However, how cis- trans- act across continuous trajectories cellular differentiation vivo is poorly understood. Here, we quantify allele-specific expression during spermatogenic at single-cell resolution an F1 hybrid mouse system, allowing for the comprehensive characterisation trans -genetic effects, including their dynamics differentiation. Collectively, almost half genes...