A5077222290- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Peptidase Inhibition and Analysis
- Pulmonary Hypertension Research and Treatments
- Cancer Mechanisms and Therapy
- Genomics and Chromatin Dynamics
- Pancreatic and Hepatic Oncology Research
- Pluripotent Stem Cells Research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer-related Molecular Pathways
- Chromatin Remodeling and Cancer
- Pleural and Pulmonary Diseases
- Occupational and environmental lung diseases
- Lung Cancer Research Studies
- Data Visualization and Analytics
- Cancer Cells and Metastasis
- Multiple Myeloma Research and Treatments
- Chromosomal and Genetic Variations
- Protein Degradation and Inhibitors
- Neuroendocrine Tumor Research Advances
- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- Complex Network Analysis Techniques
- Renal and related cancers
University of Oxford
2019-2024
Nuffield Orthopaedic Centre
2023-2024
University of Cambridge
2022-2024
Southern University of Science and Technology
2023
Wenzhou-Kean University
2023
Addenbrooke's Hospital
2022
Oxford University Hospitals NHS Trust
2018
University of Haifa
2014-2015
Stem cells undergo cellular division during their differentiation to produce daughter with a new identity. However, the epigenetic events and molecular mechanisms occurring between consecutive cell divisions have been insufficiently studied due technical limitations. Here, using FUCCI reporter we developed cell-cycle synchronised human pluripotent stem (hPSC) system for uncovering epigenome transcriptome dynamics first two leading definitive endoderm. We observed that transcription of key...
Abstract Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression multiple clinical cohorts comprising 402 primary, locally recurrent metastatic NPCs. We show that SSTR2 induced by Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) via NF-κB pathway. Using cell-based preclinical...
Modifications of histone tails, including lysine/arginine methylation, provide the basis a "chromatin or code". Proteins that contain "reader" domains can bind to these modifications and form specific effector complexes, which ultimately mediate chromatin function. The spindlin1 (SPIN1) protein contains three Tudor methyllysine/arginine reader was identified as putative oncogene transcriptional coactivator. Here we report SPIN1 chemical probe inhibitor with low nanomolar in vitro activity,...
The lethality, chemoresistance and metastatic characteristics of cancers are associated with phenotypically plastic cancer stem cells (CSCs). How the non-cell autonomous signalling pathways cell-autonomous transcriptional machinery orchestrate cell-like CSCs is still poorly understood. Here we use a quantitative proteomic approach for identifying secreted proteins in pancreatic cancer. We uncover that E2F1/4-pRb/RBL2 axis balances non-cell-autonomous healthy ductal but becomes deregulated...
Abstract Pancreatic cancer (PC), one of the most aggressive and life-threatening human malignancies, is known for its resistance to cytotoxic therapies. This increasingly ascribed subpopulation undifferentiated cells, as pancreatic stem cells (PCSCs), which display greater evolutionary fitness than other tumor evade effects chemotherapy. PCSCs are crucial relapse they possess ‘stem cell-like’ features that characterized by self-renewal differentiation. However, molecular mechanisms maintain...
The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence cancer stem-like cells (CSCs) that respond poorly current chemotherapy regimens. epigenetic mechanisms regulating CSCs are currently insufficiently understood, which hampers development novel strategies for eliminating CSCs.
The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety conditions, both benign malignant, including mesothelioma, can affect this tissue. lack knowledge concerning mesothelial stromal cells comprising pleura has hampered development targeted therapies. Here, we present first comprehensive single-cell transcriptomic atlas human parietal demonstrate its utility in elucidating biology. We confirm presence known universal fibroblasts describe novel,...
The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence cancer stem-like cells (CSCs) that respond poorly current chemotherapy regimens. By small molecule compound screening targeting 142 epigenetic enzymes, we identified bromodomain-containing protein BRD9, a component BAF histone remodelling complex, key chromatin regulator orchestrate stemness CSCs via cooperating with TGFβ/Activin-SMAD2/3 signalling pathway. Inhibition and genetic ablation BDR9 block...
Recently developed latest version of the sequence-directed single-base resolution nucleosome mapping reveals existence strong nucleosomes and chromatin columnar structures (columns). Broad application this simple technique for further studies chromosome structure requires some basic understanding as to how it works what information affords. The paper provides such an introduction method. oscillating maps singular nucleosomes, short long oligonucleosome columns, are explained, well on...
The bulk of strong nucleosomes (SNs, with visibly periodic DNA sequences) is described by consensus pattern 5 or 6 base runs purines alternating similar pyrimidines – RR/YY SNs. Yet, the strongest known nucleosome positioning sequence, 601 clone Lowary and Widom, rather repetition TA dinucleotides following one another every 10 bases. We located “601”-like TA-periodic sequences in genome A. thaliana. Several families such are discovered repeating almost exclusively centromeres. Thus, while...
Abstract Tissue formation and organ homeostasis is achieved by precise coordination of proliferation differentiation stem cells progenitors. While deregulation these processes can result in degenerative disease or cancer, their molecular interplays remain unclear. Here we show that the switch human pluripotent cell (hPSC) self-renewal to associated with induction distinct Cyclin Dependent Kinase Inhibitors (CDKIs). In hPSCs, Activin/Nodal/TGFβ signalling maintains CDKIs a poised state via...
Abstract Tissue formation and organ homeostasis are achieved by precise coordination of proliferation differentiation stem cells progenitors. While deregulation these processes can result in degenerative disease or cancer, their molecular interplays remain unclear. Here we show that the switch human pluripotent cell (hPSC) self-renewal to is associated with induction distinct cyclin-dependent kinase inhibitors (CDKIs). In hPSCs, Activin/Nodal/TGFβ signaling maintains CDKIs a poised state via...
The retinoblastoma family proteins (RBs) and E2F transcription factors are cell-autonomous regulators of cell-cycle progression, but they also impact fate choice in addition to tumor suppression. range mechanisms involved remains be uncovered. Here, we show that RBs, particularly RBL2/p130, repress WNT ligands such as WNT4 WNT8A, thereby directing ectoderm specification between neural crest neuroepithelium. RBL2 achieves this function through cell-cycle-dependent cooperation with E2Fs GCN5...
Modifications of histone tails, including lysine/arginine methylation, provide the basis a 'chromatin or code'. Proteins that contain 'reader' domains can bind to these modifications and form specific effector complexes, which ultimately mediate chromatin function. The spindlin1 (SPIN1) protein contains three Tudor methyllysine/arginine reader was identified as putative oncogene transcriptional co-activator. Here we report SPIN1 chemical probe inhibitor with low nanomolar in vitro activity,...
An evolutionary network (EN) in formatted protein sequence space is a very large graph representing information about similarity of relatively short fragments.This can be used for detecting hidden relatedness between proteins, which highly significant annotation.Effective EN analysis requires an appropriate clustering approach.Based on the fact that biological strongly dependent number independent nodes connections, we develop method capable to produce quality clusters members have...
<b>Rationale:</b> Pulmonary veno-occlusive disease (PVOD) is an incurable condition characterised by the progressive remodelling of pulmonary veins, venules and capillaries. The resulting hypertension leads to right ventricular hypertrophy, death within 1-2 years if untreated. Biallelic mutations in stress sensing kinase, EIF2AK4 (GCN2), are main genetic cause PVOD. We hypothesized that loss GCN2 may lead a pro-inflammatory phenotype which be contributing development <b>Results &...
<title>Abstract</title> Tumorigenesis leads to the dedifferentiation of some cancer cells partly resemble stem cells. The maintenance circuitries and epigenetic regulatory complexes that regulate this cell-like state known as (CSCs) are largely unclear. Here we aimed find strategies for eliminating CSCs in pancreatic (PDAC), one most metastatic lethal cancers human. Proteomic analyses SMAD2/3 cofactors screening CSC self-renewal regulators uncovered BAZ2A SUV39H1 therapeutic targets...
Modifications of histone tails, including lysine/arginine methylation, provide the basis a 'chromatin or code'. Proteins that contain 'reader' domains can bind to these modifications and form specific effector complexes, which ultimately mediate chromatin function. The spindlin1 (SPIN1) protein contains three Tudor methyllysine/arginine reader was identified as putative oncogene transcriptional co-activator. Here we report SPIN1 chemical probe inhibitor with low nanomolar in vitro activity,...
Lysine and arginine methylation are amongst the most frequent modifications on unstructured histone tails incombination with other provide basis for a combinatorial 'chromatin or code'. Recognition of modifiedhistone residues is accomplished in specific manner by 'reader' domains that recognize chromatin modifications, allowing forassociation effector complexes mediate functions. The methyl-lysine methyl-arginine reader domainprotein SPINDLIN1 (SPIN1) belongs to family 5 human genes, has...
ABSTRACT The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety conditions, both benign malignant including mesothelioma, can affect this tissue. lack knowledge concerning mesothelial stromal cells comprising pleura has hampered development targeted therapies. Here we present first comprehensive single cell transcriptomic atlas human parietal demonstrate its utility in elucidating biology. We confirm presence known universal fibroblasts describe novel,...
<h3>Introduction</h3> Pulmonary veno-occlusive disease (PVOD) is an incurable condition characterised by the progressive remodelling and narrowing of small pulmonary veins, venules capillaries. This leads to right ventricular hypertrophy, hypertension, death within 1–2 years if untreated. In 2014, homozygous mutations in stress sensing kinase GCN2 were shown be main genetic cause PVOD. activated amino acid starvation phosphorylates alpha subunit eIF2 which reduces global translation while...
Pulmonary arterial hypertension (PAH) is a rare and fatal lung disease. To date, in only third of patients, the cause can be attributed to genetic variation protein-coding space. The sequencing 15,000 whole genomes by NIHR BioResource – Rare Diseases (NBR), including ~1,200 PAH samples, provides an unprecedented opportunity estimate contribution regulatory genome development PAH. This work aims determine whether sequence-based predictions epigenetic features used narrow down possible regions...