A5036989588- Cell Image Analysis Techniques
- Digital Imaging for Blood Diseases
- Image Processing Techniques and Applications
- Blood groups and transfusion
- Autophagy in Disease and Therapy
- Color Science and Applications
- Platelet Disorders and Treatments
- Leprosy Research and Treatment
- Mitochondrial Function and Pathology
- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Radiomics and Machine Learning in Medical Imaging
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Blood Coagulation and Thrombosis Mechanisms
- Receptor Mechanisms and Signaling
- ATP Synthase and ATPases Research
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Genetic Neurodegenerative Diseases
- Amino Acid Enzymes and Metabolism
University College London
2016-2025
MRC Laboratory for Molecular Cell Biology
2016-2025
Medical Research Council
2011-2022
Agency for Science, Technology and Research
2010-2011
Bioinformatics Institute
2010-2011
Kyoto University
2003-2008
Magyar Agrár- és Élettudományi Egyetem
2003
Lymph nodes (LNs) act as filters, constantly sampling peripheral cues. This is facilitated by the conduit network, a tubular structure of aligned extracellular matrix (ECM) fibrils ensheathed fibroblastic reticular cells (FRCs). LNs undergo rapid 3- to 5-fold expansion during adaptive immune responses, but these ECM-rich structures are not permanently damaged. Whether flow or filtering function affected LN unknown. Here, we show that conduits partially disrupted acute expansion, FRC-FRC...
Tumor growth is driven by continued cellular and proliferation. Cyclin-dependent kinase 7's (CDK7) role in activating mitotic CDKs global gene expression makes it therefore an attractive target for cancer therapies. However, what cells particularly sensitive to CDK7 inhibition (CDK7i) remains unclear.Here, we address this question. We show that CDK7i, samuraciclib, induces a permanent cell-cycle exit, known as senescence, without promoting DNA damage signaling or cell death. A chemogenetic...
Weibel-Palade bodies (WPBs), endothelial-specific secretory granules that are central to primary hemostasis and inflammation, occur in dimensions ranging between 0.5 5 μm. How their size is determined whether it has a functional relevance at present unknown. Here, we provide evidence for dual role of the Golgi apparatus controlling these carriers. At ministack level, cisternae constrain nanostructures ("quanta") von Willebrand factor (vWF), main WPB cargo. The ribbon architecture then allows...
Abstract Post-translational modifications are necessary for collagen precursor molecules (procollagens) to acquire final shape and function. However, the mechanism contribution of that occur outside endoplasmic reticulum Golgi not understood. We discovered VIPAR, with its partner proteins, regulate sorting lysyl hydroxylase 3 (LH3, also known as PLOD3) into newly identified post-Golgi IV carriers VIPAR-dependent is essential modification lysines in multiple types. Identification structural...
Recent work established DNA replication stress as a crucial driver of genomic instability and key event at the onset cancer. Post-translational modifications play an important role in cellular response to by regulating activity components prevent replication-stress-induced damage. Here, we establish far greater for transcriptional control determining outcome events than previously suspected. Sustained E2F-dependent transcription is both required sufficient many checkpoint functions,...
The canine transmissible venereal tumor (CTVT) is a clonally cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylation, and functional pathway analyses on serial biopsies of vincristine-treated CTVTs found occurs in sequential steps; activation innate immune system host epithelial tissue remodeling followed by infiltration tumor, arrest cell cycle, repair damage. identified...
Mitochondrial dysfunction is implicated in many neurodegenerative diseases including Parkinson's disease (PD). Induced pluripotent stem cells (iPSCs) provide a unique cell model for studying neurological diseases. We have established high-content assay that can simultaneously measure mitochondrial function, morphology and viability iPSC-derived dopaminergic neurons. iPSCs from PD patients with mutations SNCA unaffected controls were differentiated into neurons, seeded 384-well plates stained...
Abstract Aims Genetic and pharmacological inhibition of mitochondrial fission induced by acute myocardial ischaemia/reperfusion injury (IRI) has been shown to reduce infarct size. The clinically used anti-hypertensive heart failure medication, hydralazine, is known have anti-oxidant anti-apoptotic effects. Here, we investigated whether hydralazine confers cardioprotection inhibiting Drp1-mediated fission. Methods results Pre-treatment with was inhibit both membrane depolarisation oxidative...
Objective Salmonella enterica infections can lead to Reactive Arthritis (ReA), which exhibit an association with human leucocyte antigen (HLA)-B*27:05, a molecule prone misfolding and initiation of the unfolded protein response (UPR). This study examined how HLA-B*27:05 expression UPR affect life-cycle within epithelial cells. Methods Isogenic cell lines expressing two copies either control HLA-B*35:01 heavy chain (HC) were generated determine effect on infection life-cycle. A line...
Cardiomyocytes from human embryonic stem cells (hESC-CMs) and induced pluripotent (hiPSC-CMs) represent new models for drug discovery.Although hypertrophy is a high-priority target, we found that hiPSC-CMs were systematically unresponsive to hypertrophic signals such as the a-adrenoceptor (aAR) agonist phenylephrine (PE) compared hESC-CMs.We investigated signaling at multiple levels understand underlying mechanism of this differential responsiveness.The expression normal 1 AR gene, ADRA1A,...
Changes in the size of cellular organelles are often linked to modifications their function. Endothelial cells store von Willebrand Factor (vWF), a glycoprotein essential haemostasis Weibel-Palade bodies (WPBs), cigar-shaped secretory granules that generated wide range sizes. We recently showed forcing changes WPBs modifies activity this cargo. now find endothelial treated with statins produce shorter and vWF they release at exocytosis displays reduced capability recruit platelets cell...
Oral presentations Session 1: Entry & uncoating O1 Host cell polo-like kinases (PLKs) promote early prototype foamy virus (PFV) replication Irena Zurnic, Sylvia Hütter, Ute Lehmann, Nicole Stanke, Juliane Reh, Tobias Kern, Fabian Lindel, Gesche Gerresheim, Martin Hamann, Erik Müllers, Paul Lesbats, Peter Cherepanov, Serrao, Alan Engelman, Dirk Lindemann O2 A novel entry/uncoating assay reveals the presence of at least two species viral capsids during synchronized HIV-1 infection Claire Da...
HIV-1 integrates more frequently into transcribed genes, however the biological significance of integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that cardiac glycoside digoxin inhibits wild-type infection potently than bearing single point mutation (N74D) in capsid protein. We confirmed repressed viral gene expression by cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and mapping infected cells...
Robust cellular models are key in determining pathological mechanisms that lead to neurotoxicity Huntington's disease (HD) and for high throughput pre-clinical screening of potential therapeutic compounds. Such exist but mostly comprise non-human or non-neuronal cells may not recapitulate the correct biochemical milieu involved pathology. We have developed a new human neuronal cell model HD, using neural stem (ReNcell VM NSCs) stably transduced express exon 1 huntingtin (HTT) fragments with...
Vitamin D is widely reported to inhibit innate immune signalling and dendritic cell (DC) maturation as a potential immunoregulatory mechanism. It not known whether vitamin has global or gene-specific effects on transcriptional responses downstream of stimulation, inhibition common different cells. We confirmed nuclear factor-κB (NF-κB) p38 mitogen-activated protein kinase (MAPK) in monocyte-derived DC (MDDC) stimulated with lipopolysaccharide (LPS). This was associated but modest attenuation...
Hermansky-Pudlak syndrome (HPS) is a recessive disorder with bleeding diathesis, which has been linked to platelet granule defects. Both granules and endothelial Weibel-Palade bodies (WPBs) are members of lysosome-related organelles (LROs) whose formation regulated by HPS protein associated complexes such as BLOC (biogenesis complex) -1, -2, -3, AP-3 (adaptor complex-3) HOPS (homotypic fusion sorting complex). Von Willebrand factor (VWF) critical hemostasis, stored in highly-multimerized...
Poxvirus egress is a complex process whereby cytoplasmic single membrane–bound virions are wrapped in cell-derived double membrane. These triple-membrane particles, termed intracellular enveloped (IEVs), released from infected cells by fusion. Whereas the wrapping membrane thought to be derived virus-modified trans-Golgi or early endosomal cisternae, cellular factors that regulate virus remain largely undefined. To identify cell required for this prototypic poxvirus, vaccinia (VACV), was...
Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation function have been identified, role lipids is almost unknown. We examined two key phosphatidylinositol kinases control 4-phosphate levels at trans-Golgi network, site biogenesis. RNA interference type II 4-kinases...
It is long established that von Willebrand factor (VWF) central to hemostasis and thrombosis. Endothelial VWF stored in cell-specific secretory granules, Weibel-Palade bodies (WPBs), organelles generated a wide range of lengths (0.5-5.0 µm). WPB size responds physiological cues pharmacological treatment, secretion from shortened WPBs dramatically reduces platelet plasma adhesion an endothelial surface.
Autophagy is an essential degradation program required for cell homeostasis. Among its functions the engulfment and destruction of cytosolic pathogens, termed xenophagy. Not surprisingly, many pathogens use various strategies to circumvent or co-opt autophagic degradation. For poxviruses, it known that infection activates autophagy, which however not successful replication. Even though these complex viruses replicate exclusively in cytoplasm, autophagy-mediated control poxvirus has been...