A5016618033- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Cancer-related Molecular Pathways
- Protein Kinase Regulation and GTPase Signaling
- Hippo pathway signaling and YAP/TAZ
- Pancreatic and Hepatic Oncology Research
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Wnt/β-catenin signaling in development and cancer
- Chemical Reactions and Isotopes
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Caveolin-1 and cellular processes
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Cellular transport and secretion
- Glioma Diagnosis and Treatment
- Herpesvirus Infections and Treatments
- Lung Cancer Treatments and Mutations
- Signaling Pathways in Disease
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Histone Deacetylase Inhibitors Research
- Cancer, Stress, Anesthesia, and Immune Response
- Melanoma and MAPK Pathways
University of Edinburgh
2012-2024
Edinburgh Cancer Research
2015-2024
Cancer Research UK Scotland Institute
2004-2023
Garvan Institute of Medical Research
2013-2023
Weatherford College
2022
MRC Institute of Genetics and Molecular Medicine
2010-2021
Medical Research Council
1988-2020
Western General Hospital
2008-2018
Tsinghua University
2016
Heriot-Watt University
2016
TP53 mutation occurs in 50–75% of human pancreatic ductal adenocarcinomas (PDAC) following an initiating activating the KRAS gene. These p53 mutations frequently result expression a stable protein, R175H , rather than complete loss protein expression. In this study we elucidate functions mutant ( Trp53 R172H ), compared to knockout fl mouse model PDAC. First find that although Kras G12D is one major oncogenic drivers PDAC, most -expressing cells are selectively lost from tissue, and those...
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...
BRAF and MEK inhibitors are effective in mutant melanoma, but most patients eventually relapse with acquired resistance, others present intrinsic resistance to these drugs. Resistance is often mediated by pathway reactivation through receptor tyrosine kinase (RTK)/SRC-family (SFK) signaling or NRAS, which drive paradoxical of the pathway. We describe pan-RAF (CCT196969, CCT241161) that also inhibit SFKs. These compounds do not activation MEK/ERK NRAS melanoma. They melanoma cells...
Abstract Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism coordinating tissue growth 1 . Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation thousands throughout proteome 1–3 How given kinase can phosphorylate specific subset at unique sites is only partially understood 4–7 Here we used combinatorial peptide arrays to profile substrate sequence specificity all human kinases....
Evidence was recently presented that herpes simplex virus type 1 (HSV-1) immunoglobulin G (IgG) Fc receptors are composed of a complex containing previously described glycoprotein, gE, and novel virus-induced polypeptide, provisionally named g70 (D. C. Johnson V. Feenstra, J. Virol. 61:2208-2216, 1987). Using monoclonal antibody designated 3104, which recognizes g70, in conjunction with antipeptide sera mutants unable to express or we have mapped the gene encoding US7 open reading frame...
Integrin-associated focal adhesions not only provide adhesive links between cellular actin and extracellular matrix but also are sites of signal transmission into the cell interior. Many responses through adhesion kinase (FAK), often by integrin-induced autophosphorylation FAK or phosphorylation Src family kinases. Here, we used an interfering mutant (4-9F-FAK) to show that Src-dependent is required for turnover migration, controlling assembly a calpain 2/FAK/Src/p42ERK complex, activation,...
We have generated mice with a floxed fak allele under the control of keratin-14-driven Cre fused to modified estrogen receptor ( ER T2 ). 4-Hydroxy-tamoxifen treatment induced deletion in epidermis, and suppressed chemically skin tumor formation. Loss once benign tumors had formed inhibited malignant progression. Although was associated reduced migration keratinocytes vitro, we found no effect on wound re-epithelialization vivo. However, increased keratinocyte cell death observed after vitro...