A5024442204- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Genetics, Bioinformatics, and Biomedical Research
- RNA Research and Splicing
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- FOXO transcription factor regulation
- NF-κB Signaling Pathways
- Peptidase Inhibition and Analysis
- Gene expression and cancer classification
- Animal Genetics and Reproduction
- Cancer-related molecular mechanisms research
- Esophageal Cancer Research and Treatment
- Protein Degradation and Inhibitors
- RNA and protein synthesis mechanisms
- Single-cell and spatial transcriptomics
- Protein Kinase Regulation and GTPase Signaling
- interferon and immune responses
- Chromosomal and Genetic Variations
- Molecular Biology Techniques and Applications
University of Manchester
2016-2025
Manchester Academic Health Science Centre
2017-2024
University of Tsukuba
2024
Columbia University
2019
Université de Lille
2019
Centre National de la Recherche Scientifique
2019
Unité de Glycobiologie Structurale et Fonctionnelle
2019
University of Cambridge
2017
MRC Cancer Unit
2017
University of Coimbra
2016-2017
The ternary complex factor (TCF) subfamily of ETS-domain transcription factors bind with serum response (SRF) to the element (SRE) and mediate increased gene expression. TCF protein Elk-1 is phosphorylated by JNK ERK groups mitogen-activated (MAP) kinases causing DNA binding, formation, transcriptional activation. Activated SRE-dependent expression induced in cells treated interleukin-1 after treatment phorbol ester. therefore integrates MAP kinase signaling pathways vivo coordinate...
The transcription factors Elk-1 and SAP-1 bind together with serum response factor to the element present in c-fos promoter mediate increased gene expression. ERK, JNK, p38 groups of mitogen-activated protein (MAP) kinases phosphorylate activate a variety extracellular stimuli. In contrast, is activated by ERK MAP but not JNK. proinflammatory cytokine interleukin-1 (IL-1) activates JNK induces transcriptional activity SAP-1. These effects IL-1 appear be mediated Rho family GTPases. To...
Abstract CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost Barrett’s esophagus (BE) esophageal adenocarcinoma (EAC). How other gene co-deletions affect EAC evolution remains understudied. We explored the effects of loss EACs cancer progressor non-progressor BEs with matched genomic, transcriptomic clinical data. Despite its driver role, BE prevents initiation by counterselecting subsequent TP53 alterations. predict poor patient survival but not through...
The phosphorylation of transcription factors by mitogen-activated protein kinases (MAP) is a pivotal event in the cellular response to activation MAP kinase signal transduction pathways. Mitogenic and stress stimuli activate different pathways lead distinct groups target proteins. Elk-1 targeted three In this study, we demonstrate that ERK2 domain which from, located N-terminally to, its phosphoacceptor motifs. Targeting via essential for efficient rapid vitro full vivo. Specific residues...
Mitogen-activated protein (MAP) kinase-mediated signalling to the nucleus is an important event in conversion of extracellular signals into a cellular response. However, existence multiple MAP kinases which phosphorylate similar phosphoacceptor motifs poses problem maintaining substrate specificity and hence correct biological Both signal-regulated kinase (ERK) c-Jun NH2-terminal (JNK) subfamilies use second determinant require docking their transcription factor substrates achieve maximal...
Embryonic stem cells (ESCs) are unique in that they have the capacity to differentiate into all of cell types body. We know a lot about complex transcriptional control circuits maintain naive pluripotent state under self-renewing conditions but comparatively less how exit from this response differentiation stimuli. Here, we examined role Otx2 process mouse ESCs and demonstrate it plays leading remodeling gene regulatory networks as ground pluripotency. drives enhancer activation through...
Transcriptional induction of the c-fos gene in response to epidermal growth factor stimulation is mediated part by a ternary nucleoprotein complex within promoter consisting serum (SRF), p62TCF/Elk-1 and element (SRE). Both SRF contact DNA bind cooperative manner SRE. In this study, we demonstrate that Elk-1 interact directly absence A 30-amino-acid peptide from (B-box) both necessary sufficient mediate protein-protein contacts with SRF. Moreover, B-box enable SRF-dependent binding an...
AbstractThe transcriptional status of eukaryotic genes is determined by a balance between activation and repression mechanisms. The nuclear hormone receptors represent classical examples transcription factors that can regulate this recruiting corepressor coactivator complexes in ligand-dependent manner. Here, we demonstrate the equilibrium via single factor, Elk-1, altered following Erk mitogen-activated protein kinase cascade. In addition to its C-terminal domain, Elk-1 contains an...
The Id subfamily of helix-loop-helix (HLH) proteins plays a fundamental role in the regulation cellular proliferation and differentiation. major mechanism by which are thought to inhibit differentiation is through interaction with other HLH inhibition their DNA-binding activity. However, have also been shown interact involved regulating differentiation, suggesting more widespread regulatory function. In this study we demonstrate functional interactions between members Pax-2/-5/-8...
Transcription factors play an important role in orchestrating the activation of specific networks genes through targeting their proximal promoter and distal enhancer regions. However, it is unclear how specificity downstream responses maintained by individual members transcription-factor families and, most cases, what target repertoire is. We have used ChIP-chip analysis to identify ETS-domain transcription factor ELK1. Two distinct modes ELK1 gene selection are identified; first involves...
Osteopontin (OPN) is an important component of the extracellular matrix (ECM), which promotes liver fibrosis and has been described as a biomarker for its severity. Previously, we have demonstrated that Sex-determining region Y-box 9 (SOX9) ectopically expressed during activation hepatic stellate cells (HSC) when it responsible production type 1 collagen, causes scar formation in fibrosis. Here, demonstrate SOX9 regulates OPN. During normal development mature liver, OPN are coexpressed...
There are numerous forkhead transcription factors in mammalian cells but we know little about the molecular functions of majority these. FOXK2 is a ubiquitously expressed family member suggesting an important function across multiple cell types. Here, show that binds to SIN3A and PR-DUB complexes. The complex contains tumour suppressor protein, deubiquitinase BAP1. recruits BAP1 DNA, promotes local histone deubiquitination causes changes target gene activity. Our results therefore provide...
ATAC-seq is a recently developed method to identify the areas of open chromatin in cell. These regions usually correspond active regulatory elements and their location profile unique given cell type. When done at single-cell resolution, provides an insight into cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying genomic sites each cells. This paper presents Scasat (single-cell analysis tool), complete pipeline process scATAC-seq data with simple steps....