A5010386483- Cell Adhesion Molecules Research
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chemokine receptors and signaling
- Pancreatic and Hepatic Oncology Research
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- Neuroblastoma Research and Treatments
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- S100 Proteins and Annexins
- Neuroendocrine Tumor Research Advances
- Hippo pathway signaling and YAP/TAZ
- Cellular transport and secretion
- Cancer-related Molecular Pathways
- RNA Research and Splicing
- interferon and immune responses
- Pancreatic function and diabetes
- Ubiquitin and proteasome pathways
- Adenosine and Purinergic Signaling
- Neonatal Health and Biochemistry
- RNA modifications and cancer
- CAR-T cell therapy research
University Medical Center Groningen
2025
Cancer Research UK Scotland Institute
2023-2024
Cancer Research UK
2024
University of Glasgow
2020-2023
Abstract MYC is implicated in the development and progression of pancreatic cancer, yet precise level deregulation required to contribute tumor has been difficult define. We used modestly elevated expression human MYC, driven from Rosa26 locus, investigate phenotypes arising mice an approximation trisomy. show that this alone suffices drive neuroendocrine tumors, accelerate KRAS-initiated precursor lesions metastatic ductal adenocarcinoma (PDAC). Our phenotype exposed suppression type I...
Abstract While the effect of amplification-induced oncogene expression in cancer is known, impact copy-number gains on “bystander” genes less understood. We create a comprehensive map dosage compensation by integrating and copy number profiles from over 8000 tumors The Cancer Genome Atlas cell lines Cell Line Encyclopedia. Additionally, we analyze 17 open reading frame screens to identify toxic cells when overexpressed. Combining these approaches, propose class ‘Amplification-Related Gain Of...
Abstract Neutrophils are a highly heterogeneous cellular population. However, thorough examination of the different transcriptional neutrophil states between health and malignancy has not been performed. We utilized single-cell RNA sequencing human murine datasets, both publicly available independently generated, to identify transcriptomic subtypes developmental lineages in malignancy. Datasets lung, breast, colorectal cancer were integrated establish validate gene signatures. Pseudotime...
The AMP‐activated protein kinase (AMPK)‐related NUAK1 (NUAK family SNF1‐like 1) has emerged as a potential vulnerability in MYC‐dependent cancer but the biological roles of different settings are poorly characterised, and spectrum types that exhibit requirement for is unknown. Unlike canonical oncogenes, rarely mutated appears to function an obligate facilitator rather than driver per se . Although numerous groups have developed small‐molecule NUAK inhibitors, circumstances would trigger...
Abstract Neutrophils are thought to be critical the process whereby breast cancers establish an immunosuppressive and tumour cell nurturing ‘pre-metastatic’ niche before overt metastasis can detected. However, spatial localization of neutrophils their interaction with other types in lung pre-metastatic is not well described. We used a spontaneously metastatic mammary cancer model combined multiplexed three- four-dimensional imaging approach investigate behaviour niche. Volume fixed tissue...
<p>Loss of neutrophil-specific CXCR2 attenuates suppression T-cell proliferation in neutrophils from the metastatic niche mice bearing tumors. Neutrophils liver and blood littermate either <i>Mrp8-Cre-Cxcr2<sup>+/+</sup></i> (WT) or <i>Mrp8-Cre-Cxcr2</i><sup>fl/fl</sup> (CXCR2fl) were harvested 28 days following intrasplenic injection villinCreER...
<p>Figure S8. CXCR2-lacking neutrophils from healthy mice exhibit no functional differences wild type in co-culture with KPN organoids</p>
<p>Characterization of neutrophil signatures and lineages in health PTs. <b>A,</b> Uniform Manifold Approximation Projection for Dimension (UMAP) plot healthy neutrophils grouped by tissue type. BM: bone marrow, SP: spleen, L: lung, BL: blood. <b>B,</b> UMAP plots tumor-derived type Seurat clusters (0–15). blood, L_AC: lung adenocarcinoma, KPN: colorectal cancer with <i>Kras</i>, <i>Trp53</i> Notch mutations. <b>C,</b> mouse...
<div>Abstract<p>Neutrophils are a highly heterogeneous cellular population. However, thorough examination of the different transcriptional neutrophil states between health and malignancy has not been performed. We utilized single-cell RNA sequencing human murine datasets, both publicly available independently generated, to identify transcriptomic subtypes developmental lineages in malignancy. Datasets lung, breast, colorectal cancer were integrated establish validate gene...
<p>CD4<sup>+</sup> T cells are transcriptomically altered in metastasis. <b>A</b> and <b>B,</b> UMAP plots of CD4<sup>+</sup> CD8<sup>+</sup> PT LM grouped by cell type tumor type, respectively. <b>C,</b> Differential gene expression compared with PT. <b>D</b> <b>E,</b> GO KEGG analyses metastatic cells. <b>F</b> <b>G,</b> Global cell-cell communication network the...
<p>Characterization of neutrophils in metastasis. <b>A,</b> UMAP CRCLM. <b>B,</b> Coexpression H_enriched and T_enriched signatures. One cluster is not enriched for either signature (blue arrow). <b>C</b> <b>D,</b> Unsupervised pseudotime analysis estimated smoothers TXNIP expression over the different numbered lineages. <b>E,</b> CXCR2. <b>F</b> <b>G,</b> Expression CXCL8 pseudotime....
<p>Figure S9: Summary of findings.</p>
<p>Figure S6. L-R interactions from the significant signalling pathways that mediate communication between macrophages and other immune-cell subtypes in CRCLM.</p>
<p>Figure S4. cell-cell communication networks at a signalling pathway level.</p>
<p>Figure S7. Exogenous application of IL-1β and GM-CSF alter transcription Cxcr2 Txnip in wild type neutrophils ex vivo.</p>
<p>Figure S4. cell-cell communication networks at a signalling pathway level.</p>
<p>Figure S3. Scoring for the M_enriched signature in NSCLC primary tumour dataset and outgoing signals from cell populations CRCLM.</p>
<div>Abstract<p>Neutrophils are a highly heterogeneous cellular population. However, thorough examination of the different transcriptional neutrophil states between health and malignancy has not been performed. We utilized single-cell RNA sequencing human murine datasets, both publicly available independently generated, to identify transcriptomic subtypes developmental lineages in malignancy. Datasets lung, breast, colorectal cancer were integrated establish validate gene...
<p>Description of colorectal cancer mouse models used</p>
<p>Signaling patterns in CRCLM. <b>A</b> and <b>B,</b> Outgoing incoming signaling <b>C,</b> Cellular roles as dominant senders (sources) receivers (targets) CRCPT LM. dataset did not contain any Tregs or neutrophils. <b>D,</b> UMAP plot of neutrophil subtypes <b>E,</b> Interaction strength the global communication between neutrophil, T-cell, macrophage subtypes. <b>F–I,</b> signal strengths from TXNIP+...
<p>Figure S5. L-R interactions from the significant signalling pathways that mediate neutrophil and T-cell communication in CRCLM.</p>