A5059216269- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Total Knee Arthroplasty Outcomes
- Knee injuries and reconstruction techniques
- Osteoarthritis Treatment and Mechanisms
- Chromatin Remodeling and Cancer
- Cancer, Hypoxia, and Metabolism
- Protein Degradation and Inhibitors
- Orthopaedic implants and arthroplasty
- Neurotransmitter Receptor Influence on Behavior
- Pharmacological Effects and Toxicity Studies
- Cancer Research and Treatments
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Lower Extremity Biomechanics and Pathologies
- Attention Deficit Hyperactivity Disorder
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Dental Implant Techniques and Outcomes
- Orthopedic Surgery and Rehabilitation
- Orthopedic Infections and Treatments
- Neural and Behavioral Psychology Studies
- Sports injuries and prevention
- Bone Tissue Engineering Materials
- ATP Synthase and ATPases Research
University of Cambridge
2023-2024
Brain Tumour Research
2023-2024
University of Liverpool
2015-2023
Manchester University NHS Foundation Trust
2023
Royal Liverpool and Broadgreen University Hospital NHS Trust
2023
University of Manchester
2021-2023
Aintree University Hospitals NHS Foundation Trust
2015-2023
Douglas Mental Health University Institute
2018-2023
McGill University
2017-2023
Henry Royce Institute
2021-2022
Abstract Pediatric high-grade gliomas (pHGG) are lethal, incurable brain tumors frequently driven by clonal mutations in histone genes. They often harbor a range of additional genetic alterations that correlate with different ages, anatomic locations, and tumor subtypes. We developed models representing 16 pHGG subtypes combinations targeted to specific regions. Tumors varying latencies cell lines derived from these engrafted syngeneic, immunocompetent mice high penetrance. Targeted drug...
<p>Bulk RNAseq projections by ssGSEA.</p>
<p>Orthotopic engraftment of cell lines derived from Foxr2 p53LOF murine model.</p>
<p><i>Foxr2</i> is oncogenic in the ventral telencephalon mice. <b>A,</b> Schematic describing IUE-based strategy to model <i>FOXR2</i>-driven brain tumors. PiggyBac and CRISPR vectors are delivered into neural stem cells GEs at E12.5. After birth, mice develop tumors euthanized when neurologic symptoms become apparent. <b>B,</b> Representative brightfield (BF) fluorescence (GFP) images of a GFP+ <i>Foxr2</i>-driven tumor...
<p>Foxr2 chromatin binding sites in <i>Foxr2</i> p53<sup>LOF</sup> neurosphere show enrichment ETS and glial pathways. <b>A,</b> Validation of FOXR2 overexpression p53 downregulation <i>ex vivo</i><i>Foxr2</i> neurospheres by qRT-PCR. <b>B,</b> <i>Nkx2-1</i>, <i>Lhx6</i>, <i>Dlx5</i>, <i>Dlx6</i>, <i>Emx2</i>, <i>Sox10</i>,...
<p><i>FOXR2</i> does not induce expression of MGE or EC-NB TFs. <b>A,</b> Bulk RNA-seq telencephalon patterning Top and third rows, tumor samples from this study cohort. Second row, (Gartlgruber colleagues, ref. <a href="#bib21" target="_blank">21</a>) subset to high risk, stage 4 with <i>FOXR2</i> (normalized >2). Bottom H9 human NSCs transduced HA-FOXR2 controls HcRed (Tsai href="#bib7" target="_blank">7</a>). All box plots...
<p>Mouse models transcriptomically recapitulate human NB-FOXR2. <b>A,</b> Heatmap showing CNVs in <i>Foxr2</i> p53<sup>LOF</sup> and alone models, computed with inferCNV. <b>B,</b> Top, Uniform Manifold Approximation Projection (UMAP) joint representation of mouse model single-cell datasets (<i>n</i> = 3) without integration or batch correction. Cells colored by broad cell class derived from automated type annotation,...
<p>NB-FOXR2 tumors transcriptionally resemble interneurons and OPC cells. <b>A,</b><i>t</i>-Distributed stochastic neighbor embedding (<i>t</i>-SNE) of bulk RNA-seq profiles pediatric brain (left) with stage 4 high-risk EC-NBs from Gartlgruber colleagues (ref. <a href="#bib21" target="_blank">21</a>; right) using ssGSEA scores for <i>N</i> = 374 cell type–specific gene signatures reference scRNA-seq datasets....
<p>Quality control (QC) metrics and copy-number variation for scRNAseq datasets of NB-FOXR2 patient tumors.</p>
<p>NB-FOXR2 express a transcription factor fingerprint of the medial ganglionic eminence.</p>
<p>Transcription factor (TF) patterning in normal reference datasets.</p>
<p>Mouse models transcriptomically recapitulate human NB-FOXR2</p>
<p>NB-FOXR2 tumors transcriptionally resemble interneurons and oligodendrocyte precursor cells.</p>