A5012509728- Histone Deacetylase Inhibitors Research
- Angiogenesis and VEGF in Cancer
- Endoplasmic Reticulum Stress and Disease
- Galectins and Cancer Biology
- Peptidase Inhibition and Analysis
- Mesenchymal stem cell research
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Congenital heart defects research
- Signaling Pathways in Disease
- Autophagy in Disease and Therapy
- RNA regulation and disease
- Coronary Interventions and Diagnostics
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Atherosclerosis and Cardiovascular Diseases
- Protein Degradation and Inhibitors
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Nuclear Receptors and Signaling
- Ubiquitin and proteasome pathways
- 14-3-3 protein interactions
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
King's College London
2015-2024
British Heart Foundation
2011-2024
Center for Vascular Biology Research
2019
Faculty (United Kingdom)
2018
Peking University
2010-2017
The King's College
2016
Manchester Metropolitan University
2016
Queen's University Belfast
2013-2015
Queen Mary University of London
2011-2015
William Harvey Research Institute
2011-2015
The generation of induced pluripotent stem (iPS) cells is an important tool for regenerative medicine. However, the main restriction risk tumor development. In this study we found that during early stages somatic cell reprogramming toward a state, specific gene expression patterns are altered. Therefore, developed method to generate partial-iPS (PiPS) by transferring four factors (OCT4, SOX2, KLF4, and c-MYC) human fibroblasts 4 d. PiPS did not form tumors in vivo clearly displayed potential...
Reendothelialization involves endothelial progenitor cell (EPC) homing, proliferation, and differentiation, which may be influenced by fluid shear stress local flow pattern. This study aims to elucidate the role of laminar on embryonic stem (ES) differentiation underlying mechanism. We demonstrated that enhanced ES cell–derived proliferation into cells (ECs). Laminar stabilized activated histone deacetylase 3 (HDAC3) through Flk-1–PI3K–Akt pathway, in turn deacetylated p53, leading p21...
X-box binding protein 1 (XBP1) is a key signal transducer in endoplasmic reticulum stress response, and its potential role the atherosclerosis development unknown. This study aims to explore impact of XBP1 on maintaining endothelial integrity related delineate underlying mechanism. We found that was highly expressed at branch points areas atherosclerotic lesions arteries ApoE(-/-) mice, which severity lesion development. In vitro using human umbilical vein cells (HUVECs) indicated disturbed...
NADPH oxidase (Nox4) produces reactive oxygen species (ROS) that are important for vascular smooth muscle cell (SMC) behavior, but the potential impact of Nox4 in stem differentiation is unknown. When mouse embryonic (ES) cells were plated on collagen IV-coated dishes/flasks, a panel SMC-specific genes was significantly and consistently upregulated. expression markedly correlated with such gene induction as confirmed by real-time PCR, immunofluorescence, Western blot analysis. Overexpression...
Histone deacetylase 3 (HDAC3) is known to play a crucial role in the differentiation of endothelial progenitors. The HDAC3 mature cells, however, not well understood. Here, we investigated function preserving integrity areas disturbed blood flow, ie, bifurcation prone atherosclerosis development.En face staining aortas from apolipoprotein E-knockout mice revealed increased expression HDAC3, specifically these branching vivo, whereas rapid upregulation protein was observed cells exposed flow...
Background— Vascular endothelial cell growth factor plays a pivotal role in angiogenesis via regulating proliferation. The X-box binding protein 1 (XBP1) is believed to be signal transducer the endoplasmic reticulum stress response. It unknown whether there crosstalk between vascular signaling and XBP1 pathway. Methods Results— We found that induced kinase insert domain receptor internalization interaction through C-terminal with unspliced inositol requiring enzyme α reticulum, leading...
Although not fully understood, the phenotypic transition of vascular smooth muscle cells exhibits at early onset pathology aortic aneurysms. Exploring key regulators that are responsible for maintaining contractile phenotype (VSMCs) may confer homeostasis and prevent aneurysmal disease. XBP1 (X-box binding protein 1), which exists in a transcriptionally inactive unspliced form (XBP1u) spliced active (XBP1s), is component response to endoplasmic reticular stress. Compared with XBP1s, little...
Embryonic stem (ES) cells can differentiate into smooth muscle (SMCs) that be used for tissue engineering and repair of damaged organs. However, little is known about the molecular mechanisms differentiation in these cells. In present study, we found collagen IV promote ES to cell antigen-1-positive (Sca-1(+)) progenitor SMCs. Pretreatment with antibodies against significantly inhibited SMC marker expression. To further elucidate effect on induction maintenance differentiation, Sca-1(+) were...
Background— Embryonic stem cells possess the ability to differentiate into endothelium. The produce large volumes of endothelium from embryonic could provide a potential therapeutic modality for vascular injury. We describe an approach that selects endothelial using magnetic beads may be used therapeutically treat arterial Methods and Results— Large numbers (ECs) with high purity were produced Sca-1 + isolated predifferentiated (ESCs) cultured in α-MEM containing 10 ng/mL VEGF 165 minimum 21...
Rationale : Histone deacetylase (HDAC)7 is expressed in the early stages of embryonic development and may play a role endothelial function. Objective This study aimed to investigate HDAC7 cell (EC) proliferation growth underlying mechanism. Methods Results Overexpression by adenoviral gene transfer suppressed human umbilical vein (HUVEC) preventing nuclear translocation β-catenin downregulation T-cell factor-1/Id2 (inhibitor DNA binding 2) cyclin D1, leading G 1 phase elongation. Further...
Vascular endothelial cell (EC) dysfunction plays a key role in diabetic complications. This study discovers significant upregulation of Quaking-7 (QKI-7) iPS cell-derived ECs when exposed to hyperglycemia, and human iPS-ECs from patients. QKI-7 is also highly expressed coronary arterial donors, on blood vessels critical limb ischemia patients undergoing lower-limb amputation. expression tightly controlled by RNA splicing factors CUG-BP hnRNPM through direct binding. correlated with disrupted...
Previous studies have shown that integrin activation and fluid shear stress can modulate the activity of sterol regulatory element binding proteins (SREBPs) in vascular endothelial cells. We investigated role small GTPase Rho-mediated signal transduction pathway this mode SREBP activation. Fluid activates Rho downstream effectors ROCK, LIM kinase (LIMK), cofilin. The various negative mutants RhoA, LIMK, cofilin block SREBPs. stress-activated depends on S2P proteases but not caspase-3....
ATP-binding cassette transporter A1 (ABCA1) is a pivotal regulator of cholesterol efflux from cells to apolipoproteins, whereas sterol-responsive element-binding protein 2 (SREBP2) the key regulating synthesis and uptake. We investigated regulation ABCA1 by SREBP2 in vascular endothelial (ECs). Our results showed that sterol depletion activated increased its target, low density lipoprotein receptor mRNA, with concurrent decrease mRNA. Transient transfection analysis revealed decreased...
Histone deacetylases (HDACs) have a central role in the regulation of gene expression. Here we investigated whether HDAC7 has an impact on embryonic stem (ES) cell differentiation into smooth muscle cells (SMCs). ES were seeded collagen-IV-coated flasks and cultured absence leukemia inhibitory factor medium to induce SMC differentiation. Western blots double-immunofluorescence staining demonstrated that parallel expression pattern with marker genes. In ex vivo culture from SM22-LacZ...
Abstract The capability to derive endothelial cell (ECs) from induced pluripotent stem cells (iPSCs) holds huge therapeutic potential for cardiovascular disease. This study elucidates the precise role of RNA-binding protein Quaking isoform 5 (QKI-5) during EC differentiation both mouse and human iPSCs (hiPSCs) dissects how proteins can improve efficiency toward therapy important vascular diseases. represent an attractive cellular approach regenerative medicine today as they be used generate...
Recent studies have shown that Sca-1(+) (stem cell antigen-1) stem/progenitor cells within blood vessel walls may contribute to neointima formation, but the mechanism behind their recruitment has not been explored. In this work progenitor were cultivated from mouse vein graft tissue and found exhibit increased migration when cocultured with smooth muscle (SMCs) or treated SMC-derived conditioned medium. This was associated elevated levels of chemokines, CCL2 (chemokine (C-C motif) ligand 2)...
Histological assessments of synovial tissues from patients with failed CoCr alloy hip prostheses demonstrate extensive infiltration and accumulation macrophages, often loaded large quantities particulate debris. The resulting adverse reaction to metal debris (ARMD) frequently leads early joint revision. Inflammatory response starts the recruitment immune cells requires egress macrophages inflamed site for resolution reaction. Metal ions (Co2+ Cr3+) have been shown stimulate migration T...