A5068852417- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Hippo pathway signaling and YAP/TAZ
- Cancer Cells and Metastasis
- Ubiquitin and proteasome pathways
- Cellular Mechanics and Interactions
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- Genetic and Kidney Cyst Diseases
- Chromosomal and Genetic Variations
- Cancer-related Molecular Pathways
- Cellular transport and secretion
- Extracellular vesicles in disease
- Developmental Biology and Gene Regulation
- HER2/EGFR in Cancer Research
- MicroRNA in disease regulation
- RNA modifications and cancer
- Caveolin-1 and cellular processes
- Genomic variations and chromosomal abnormalities
- Lipid metabolism and biosynthesis
- Cancer Immunotherapy and Biomarkers
- Protein Degradation and Inhibitors
- Phagocytosis and Immune Regulation
Queen Mary University of London
2015-2025
Dana-Farber Cancer Institute
2008-2018
Harvard University
2007-2018
Instituto Gulbenkian de Ciência
2005-2018
University of Cambridge
2018
University of Lisbon
2018
Howard Hughes Medical Institute
2009-2014
Cancer Institute (WIA)
2014
International Charter School
2014
Multiple centrosomes in tumor cells create the potential for multipolar divisions that can lead to aneuploidy and cell death. Nevertheless, many cancer successfully divide because of mechanisms suppress mitoses. A genome-wide RNAi screen Drosophila S2 a secondary analysis defined In addition proteins organize microtubules at spindle poles, we identified novel roles assembly checkpoint, cortical actin cytoskeleton, adhesion. Using live imaging fibronectin micropatterns, found interphase shape...
Significance Ribosomes are essential intracellular machines composed of proteins and RNA molecules. The DNA sequences [i.e., ribosomal (rDNA)] encoding rRNAs tandemly repeated give rise to the nucleolus. transcribed from two array kinds (the 5S 45S arrays). Here we show that variation in rDNA arrays is tightly coupled, despite their location on different chromosomes. Our observations suggest natural selection contributes maintain balanced dosage across unlinked arrays. Finally, bisphenol A...
Abstract Centrosomes are the major microtubule organising centres of animal cells. Deregulation in their number occurs cancer and was shown to trigger tumorigenesis mice. However, incidence, consequence origins this abnormality poorly understood. Here, we screened NCI-60 panel human cell lines systematically analyse centriole structure. Our screen shows that amplification is widespread highly prevalent aggressive breast carcinomas. Moreover, identify another recurrent feature cells: size...
Centrosomal abnormalities, in particular centrosome amplification, are recurrent features of human tumors. Enforced amplification vivo plays a role tumor initiation and progression. However, occurs only subset cancer cells, thus, partly due to this heterogeneity, the contribution tumors is unknown. Here, we show that supernumerary centrosomes induce paracrine-signaling axis via secretion proteins, including interleukin-8 (IL-8), which leads non-cell-autonomous invasion 3D mammary organoids...
Bidirectional communication between cells and their surrounding environment is critical in both normal pathological settings. Extracellular vesicles (EVs), which facilitate the horizontal transfer of molecules cells, are recognized as an important constituent cell-cell communication. In cancer, alterations EV secretion contribute to growth metastasis tumor cells. However, mechanisms underlying these changes remain largely unknown. Here, we show that centrosome amplification associated with...
T cell activation is associated with a profound and rapid metabolic response to meet increased energy demands for division, differentiation development of effector function. Glucose uptake engagement the glycolytic pathway are major checkpoints this event. Here we show that low-affinity, concentration-dependent glucose transporter 2 (Glut2) regulates CD8
Fanconi anemia (FA) is a genomic instability disorder characterized by bone marrow failure and cancer predisposition. FA caused mutations in any one of several genes that encode proteins cooperating repair pathway required for cellular resistance to DNA crosslinking agents. Recent studies suggest the may also play role mitosis, since FANCD2 FANCI, 2 key proteins, are localized extremities ultrafine bridges (UFBs), which link sister chromatids during cell division. However, whether regulate...
Centrosome amplification is a common feature of human tumors. To survive, cancer cells cluster extra centrosomes during mitosis, avoiding the detrimental effects multipolar divisions. However, it unclear whether clustering requires adaptation or inherent to all cells. Here, we show that have varied abilities centrosomes. Epithelial are innately inefficient at even in presence HSET/KIFC1, which essential but not sufficient promote clustering. The E-cadherin decreases cortical contractility...
Intracellular organelle organization is conserved in eukaryotic cells and primarily achieved through active transport by motor proteins along the microtubule cytoskeleton. Microtubule post-translational modifications (PTMs) can contribute to diversity differentially regulate motor-mediated transport. Here, we show that centrosome amplification, commonly observed cancer shown promote aneuploidy invasion, induces a global change positioning towards cell periphery facilitates nuclear migration...
The forkhead transcription factor FoxM1 has been reported to regulate, variously, proliferation and/or spindle formation during the G2/M transition of cell cycle. Here we define specific functions brain development by investigation loss-of-function mutations in context Sonic hedgehog (Shh)-induced neuroproliferation cerebellar granule neuron precursors (CGNP). We show that is expressed anlagen as well postnatal proliferating CGNP and it upregulated response activated Shh signaling. To...
ABSTRACT Overexpression of the HER2 protein in breast cancer patients is a predictor poor prognosis and resistance to therapies. We used an inducible transformation system that allows investigation early molecular changes. overexpression similar levels as those observed subtype HER2-positive induced MCF10A cells resulted gross morphological changes, increased anchorage-independent growth cells, altered transcriptional programme genes associated with oncogenic transformation. Global...
Article13 January 2020Open Access Source DataTransparent process Macrophages induce malignant traits in mammary epithelium via IKKε/TBK1 kinases and the serine biosynthesis pathway Ewa Wilcz-Villega Centre for Molecular Oncology, Barts Cancer Institute, John Vane Science Centre, Queen Mary University of London, UK Search more papers by this author Edward Carter Tumour Biology, Alastair Ironside Ruoyan Xu Isabella Mataloni Julie Holdsworth William Jones Rocío Moreno Béjar Lukas Uhlik Robert B...
AbstractCorrect chromosome structure is essential to ensure faithful segregation during mitosis. Chromosome condensation occurs at the same time as cohesion released from arms of sister chromatids. It not until metaphase-anaphase transition that chromosomes lose completely, by proteolysis component cohesin complex Scc1 (Sister chromatid 1). has been shown in vertebrates Polo-like kinase, Plk1, important for this process inducing destabilization arms. still unclear if conserved other high...
Despite being a common feature of human cancer, the role supernumerary centrosomes in tumourigenesis is still poorly understood. We have recently described novel for centrosome amplification promoting cell invasion that could impact tumor progression.