A5012486076- Advanced Fluorescence Microscopy Techniques
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- Advanced Biosensing Techniques and Applications
- Cell Adhesion Molecules Research
- PI3K/AKT/mTOR signaling in cancer
- Medical Imaging Techniques and Applications
- Cell Image Analysis Techniques
- IL-33, ST2, and ILC Pathways
- Radiomics and Machine Learning in Medical Imaging
- Advanced MRI Techniques and Applications
- Lung Cancer Research Studies
- Cellular Mechanics and Interactions
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Protein Kinase Regulation and GTPase Signaling
- Single-cell and spatial transcriptomics
- Nanoplatforms for cancer theranostics
King's College London
2016-2025
Lung Institute
2025
Imperial College London
2024-2025
Age UK
2025
University College London
2015-2024
Cancer Research UK
2002-2024
Laboratory of Molecular Genetics
2024
Fukuoka Hospital
2024
Kyushu University
2024
Moderna Therapeutics (United States)
2024
Several studies suggest that RhoA and RhoC, despite their sequence similarity, have different roles in cell migration invasion, but the molecular basis for this is not known. Using RNAi, we show RhoA-depleted cells became elongated extended multiple Rac1-driven narrow protrusions 2D 3D environments, leading to increased invasion. These phenotypes were caused by combined distinct effects of Rho-regulated kinases ROCK1 ROCK2. Depletion ROCK2 induced delocalized reduced migratory polarity,...
Amplification of and oncogenic mutations in ERBB2, the gene encoding HER2 receptor tyrosine kinase, promote hyperactivation tumor growth. Here we demonstrate that ubiquitination internalization, rather than its overexpression, are key mechanisms underlying endocytosis consequent efficacy anti-HER2 antibody-drug conjugates (ADC) ado-trastuzumab emtansine (T-DM1) trastuzumab deruxtecan (T-DXd) lung cancer cell lines patient-derived xenograft models. These data translated into a 51% response...
Spatially resolved fluorescence resonance energy transfer (FRET) measured by lifetime imaging microscopy (FLIM), provides a method for tracing the catalytic activity of fluorescently tagged proteins inside live cell cultures and enables determination functional state in fixed cells tissues. Here, dynamic marker protein kinase Cα (PKCα) activation is identified exploited. Activation PKCα detected through binding phosphorylation site–specific antibodies; consequent FRET donor fluorophore on...
Förster resonance energy transfer (FRET) microscopy is a powerful technique that enables the visualization of signaling intermediates, protein interactions, and conformational biochemical status. With availability an ever-increasing collection fluorescent proteins, pairs spectrally different variants have been used for study FRET in living cells. However, suitable spectral overlap, necessary efficient FRET, limited by requirement proper emission separation. Currently represent compromises...
Aspergillus fumigatus and flavus are the most common cause of invasive mould infections worldwide carry a high mortality. Corticosteroid therapy Cushing's disease associated with an increase in aspergillosis. Corticosteroids impair immune function mammals and, specifically, conidicidal activity human macrophages, which was thought to be sufficient explanation for this increased risk. However, we have found 30-40% growth rate A. exposed pharmacological doses hydrocortisone (a glucocorticoid),...
The fibronectin (FN)-binding integrins alpha4beta1 and alpha5beta1 confer different cell adhesive properties, particularly with respect to focal adhesion formation migration. After analyses of alpha4+/alpha5+ A375-SM melanoma fragments FN that interact selectively alpha5beta1, we now report two differences in the signals transduced by each receptor underpin their specific properties. First, have a differential requirement for surface proteoglycan engagement migration; requires coreceptor...
Abstract Ability to grow under anchorage-independent conditions is one of the major hallmarks transformed cells. Key this capacity cells suppress anoikis, or programmed cell death induced by detachment from extracellular matrix. To model phenomenon in vitro, we plated Ewing tumor transferring them dishes coated with agar prevent attachment underlying plastic. This resulted marked up-regulation E-cadherin and rapid formation multicellular spheroids suspension. Addition calcium chelators,...
Both abundant epidermal growth factor receptor (EGFR or ErbB1) and high activity of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway are common therapeutically targeted in triple-negative breast cancer (TNBC). However, activation another EGFR family member [human 3 (HER3) (or ErbB3)] may limit antitumor effects these drugs. We found that TNBC cell lines cultured with HER3 ligand EGF heregulin, respectively, treated either an Akt inhibitor (GDC-0068) a PI3K (GDC-0941) had increased...
Transendothelial migration (TEM) is a tightly regulated process whereby leukocytes migrate from the vasculature into tissues. Rho guanosine triphosphatases (GTPases) are implicated in TEM, but contributions of individual family members not known. In this study, we use an RNA interference screen to identify which GTPases affect T cell TEM and demonstrate that RhoA critical for process. depletion leads loss migratory polarity; cells lack both leading edge uropod structures and, instead, have...
The immunosuppressive transmembrane protein PD-L1 was shown to traffic via the multivesicular body (MVB) and be released on exosomes. A high-content siRNA screen identified endosomal sorting complexes required for transport (ESCRT)-associated ALIX as a regulator of both EGFR activity surface presentation in basal-like breast cancer (BLBC) cells. depletion results prolonged enhanced stimulation-induced well defective trafficking through MVB, reduced exosomal secretion, its redistribution cell...
We demonstrate diffraction limited multiphoton imaging in a massively parallel, fully addressable time-resolved multi-beam microscope capable of producing fluorescence lifetime images with sub-50ps temporal resolution.This platform offers significant improvement acquisition speed over single-beam laser scanning FLIM by factor 64 without compromising either the or spatial resolutions system.We at 500 ms live cells expressing green fluorescent protein.The applicability technique to...
Abstract Tumour-associated macrophages (TAMs) play an important role in tumour progression, which is facilitated by their ability to respond environmental cues. Here we report, using murine models of breast cancer, that TAMs expressing fibroblast activation protein alpha (FAP) and haem oxygenase-1 (HO-1), are also found human represent a macrophage phenotype similar observed during the wound healing response. Importantly, expression wound-like cytokine response within clinically associated...
Quantum dots are promising candidates for single molecule imaging due to their exceptional photophysical properties, including intense brightness and resistance photobleaching. They also notorious blinking. Here we report a novel way take advantage of quantum dot blinking develop an technique in three-dimensions with nanometric resolution. We first applied this method simulated images then immobilized on microspheres. achieved resolutions (fwhm) 8-17 nm the x-y plane 58 (on coverslip) or 81...
Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in target tissue metastasis -the premetastatic niche.As crucial players pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression.We report application antibody-based single-photon emission computed tomography (SPECT) for detection S100A8/A9 vivo as imaging marker priming.Methods A...
Abstract Cancer cells tend to metastasize first tumor-draining lymph nodes, but the mechanisms mediating cancer cell invasion into lymphatic vasculature remain little understood. Here, we show that in human breast tumor microenvironment (TME), presence of increased numbers RORγt+ group 3 innate lymphoid (ILC3) correlates with an likelihood node metastasis. In a preclinical mouse model cancer, CCL21-mediated recruitment ILC3 tumors stimulated production CXCL13 by TME stromal cells, which turn...
Perivascular macrophages orchestrate the expansion of pericyte-like mesenchymal cells to create a proangiogenic niche in cancer.