A5001264667- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Spectroscopy Techniques in Biomedical and Chemical Research
- Advanced Fluorescence Microscopy Techniques
- Immune cells in cancer
- CAR-T cell therapy research
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Peptidase Inhibition and Analysis
- Spectroscopy and Chemometric Analyses
- Angiogenesis and VEGF in Cancer
- Ubiquitin and proteasome pathways
- Cell Image Analysis Techniques
- Galectins and Cancer Biology
- Gold and Silver Nanoparticles Synthesis and Applications
- Histone Deacetylase Inhibitors Research
- Hormonal Regulation and Hypertension
- Skin and Cellular Biology Research
- Phagocytosis and Immune Regulation
- bioluminescence and chemiluminescence research
- Estrogen and related hormone effects
- Eicosanoids and Hypertension Pharmacology
- Protease and Inhibitor Mechanisms
Edinburgh Cancer Research
2013-2023
Centre for Inflammation Research
2017-2023
The Queen's Medical Research Institute
2017-2023
Garvan Institute of Medical Research
2023
University of Edinburgh
2011-2022
Queen's Medical Centre
2017-2022
Institute of Genetics and Cancer
2010-2020
Medical Research Council
2017
Institute of Molecular Genetics
2011-2017
Cancer Research Center
2015
Highlights•Depletion or kinase inhibition of FAK can cause squamous cell carcinoma regression•FAK promotes tumor evasion by inducing an immuno-suppressive microenvironment•Nuclear transcription chemokines that drive recruitment Tregs•FAK-induced Tregs inhibit cytotoxic CD8+ T cells, allowing tolerance and growthSummaryFocal adhesion (FAK) anti-tumor immune evasion. Specifically, the activity nuclear-targeted in (SCC) cells drives exhaustion regulatory (Tregs) microenvironment regulating...
Glioblastoma multiforme (GBM) is an aggressive brain tumor for which current immunotherapy approaches have been unsuccessful. Here, we explore the mechanisms underlying immune evasion in GBM. By serially transplanting GBM stem cells (GSCs) into immunocompetent hosts, uncover acquired capability of GSCs to escape clearance by establishing enhanced immunosuppressive microenvironment. Mechanistically, this not elicited via genetic selection subclones, but through epigenetic immunoediting...
Abstract Most cancer-related deaths are due to the development of metastatic disease, and several new molecularly targeted agents in clinical have potential prevent disease progression. However, it remains difficult assess efficacy antimetastatic setting, an increased understanding how such work at different stages cascade is important guiding their use. We used optical window chambers combined with photobleaching, photoactivation, photoswitching quantitatively measure (a) tumor cell...
Abstract Fluorescent antimicrobial peptides are promising structures for in situ , real-time imaging of fungal infection. Here we report a fluorogenic probe to image Aspergillus fumigatus directly human pulmonary tissue. We have developed Trp-BODIPY amino acid with spacer-free C-C linkage between Trp and BODIPY fluorogen, which shows remarkable fluorescence enhancement hydrophobic microenvironments. The incorporation our short does not impair their selectivity cells, enables rapid direct...
The kinase FAK coordinates chromatin modifiers and transcription factors to orchestrate evasion of antitumor immune responses.
Objective Immunotherapy for the treatment of pancreatic ductal adenocarcinoma (PDAC) has shown limited efficacy. Poor CD8 T-cell infiltration, low neoantigen load and a highly immunosuppressive tumour microenvironment contribute to this lack response. Here, we aimed further investigate immunoregulatory function focal adhesion kinase (FAK) in PDAC, with specific emphasis on regulation type-II interferon response that is critical promoting recognition effective immunosurveillance. Design We...
Abstract Elevated levels of Src kinase expression have been found in a variety human epithelial cancers. Most notably colon cancer, elevated correlates with malignant potential and is also associated metastatic disease. Dasatinib (BMS-354825) novel, orally active, multi-targeted inhibitor that targets family kinases currently under clinical evaluation for the treatment solid tumors. However, effects dasatinib on tumors are not fully understood. We show concentrations inhibit activity do...
Stimulated Raman scattering (SRS) microscopy in tandem with bioorthogonal labelling strategies is set to revolutionise the direct visualisation of intracellular drug uptake. Rational evaluation a series Raman-active labels has allowed identification highly active which have minimal perturbation on biological efficacy parent drug. Drug uptake been correlated markers cellular composition and cell cycle status, mapped across structures using dual-colour multi-modal imaging. The phototoxicity...
The ability of tumor cells to invade and metastasize requires deregulation interactions with adjacent the extracellular matrix. A major challenge cancer biology is observe dynamics proteins involved in this process their functional physiologic context. Here, for first time, we have used photobleaching photoactivation compare mobility cell adhesion plasma membrane probes vitro tumors grown mice (in vivo). We find differences between vivo recovery two key molecules, suppressor E-cadherin...
Focal adhesion kinase (FAK) is considered intimately involved in cancer progression. Our previous research has demonstrated that overexpression of FAK an early and frequent event squamous cell carcinomas the supraglottic larynx, it associated with presence metastases cervical lymph nodes. The purpose this study was to examine functional role progression head neck (HNSCC). To end, expression FAK-related nonkinase (FRNK) or small interfering RNA (siRNA) against used disrupt FAK-induced signal...
Dynamic regulation of specific molecular processes and cellular phenotypes in live cell systems reveal unique insights into fate drug pharmacology that are not gained from traditional fixed endpoint assays. Recent advances microscopic imaging platform technology combined with the development novel optical biosensors sophisticated image analysis solutions have increased scope applications discovery. We highlight recent literature examples where has uncovered insight biological mechanism or...
The MacBlue transgenic mouse uses the Csf1r promoter and first intron to drive expression of gal4-VP16, which in turn drives a cointegrated gal4-responsive UAS-ECFP cassette. region used contains deletion 150 bp conserved covering trophoblast osteoclast-specific transcription start sites. In this study, we examined transgene embryos adult mice. embryos, ECFP was expressed large majority macrophages derived from yolk sac, as liver became major site monocytopoiesis. adults, detected at high...
Abstract Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition surrounding tumor microenvironment. Here, we report murine model skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription insulin-like growth factor binding protein 3 (IGFBP3), this SCC cell-cycle progression vivo. Furthermore, identified novel molecular complex between Runx1 nucleus cells...
Focal Adhesion Kinase (FAK) inhibitors are currently undergoing clinical testing in combination with anti-PD-1 immune checkpoint inhibitors. However, which patients most likely to benefit from FAK inhibitors, and what the optimal FAK/immunotherapy combinations are, is unknown. We identify that cancer cell expression of T-cell co-stimulatory ligand CD80 sensitizes murine tumors a inhibitor show expressed by human cells originating both solid epithelial cancers some hematological malignancies...
Focal adhesion kinase (FAK) is upregulated in several epithelial tumours and there has been considerable interest developing small molecule inhibitors of FAK. However, FAK also important adaptor functions within the cell, integrating signals from both integrins growth factors. To investigate role FAKs domain, we generated fak-deficient squamous cell carcinoma (SCC) lines. Re-expression a wild type or dead allowed us to delineate its dependent functions. In addition, used novel inhibitor...
The use of confocal and multi-photon microscopy for intra-vital cancer imaging has impacted on our understanding cell behavior interaction with the surrounding tumor microenvironment
Immunization of patients with autologous, ex vivo matured dendritic cell (DC) preparations, in order to prime antitumor T-cell responses, is the focus intense research. Despite progress and approval clinical approaches, significant enhancement these personalized immunotherapies urgently needed improve efficacy. We show that immunotherapeutic murine human DC, generated presence antimicrobial host defense peptide LL-37, have dramatically enhanced expansion differentiation cells key features...