A5060431285- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- Glioma Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- Histone Deacetylase Inhibitors Research
- PARP inhibition in cancer therapy
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- Head and Neck Cancer Studies
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
- Brain Metastases and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer-related Molecular Pathways
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- Bioinformatics and Genomic Networks
- Esophageal Cancer Research and Treatment
- CAR-T cell therapy research
- Lung Cancer Treatments and Mutations
AstraZeneca (United Kingdom)
2021-2025
Center for Translational Molecular Medicine
2022
AstraZeneca (Singapore)
2020
Wellcome/MRC Cambridge Stem Cell Institute
2013-2016
University of Cambridge
2013-2014
Bridge University
2014
Stem Cell Institute
2014
Wellcome Trust
2014
Medical Research Council
2013
National Institute for Health Research
2013
The complex anatomy of the epidermis contains multiple adult stem cell populations, but extent to which they functionally overlap during homeostasis, wound healing, and tumor initiation remains poorly defined. Here, we demonstrate that Lrig1+ve cells are highly proliferative epidermal cells. Long-term clonal analysis reveals maintain upper pilosebaceous unit, containing infundibulum sebaceous gland as independent compartments, contribute neither hair follicle nor interfollicular epidermis,...
Treatment with anti–PD-1 and anti-PD-L1 therapies has shown durable clinical benefit in non–small cell lung cancer (NSCLC). However, patients NSCLC epidermal growth factor receptor (EGFR) mutations do not respond as well to treatment without an EGFR mutation. We show that EGFR-mutated expressed higher levels of CD73 compared WT tumors expression was regulated by signaling. lines were significantly more resistant T killing through suppression proliferation function. In a xenograft mouse model...
CODEX (http://codex.stemcells.cam.ac.uk/) is a user-friendly database for the direct access and interrogation of publicly available next-generation sequencing (NGS) data, specifically aimed at experimental biologists. In an era multi-centre genomic dataset generation, provides single where these samples are collected, uniformly processed vetted. The main drive to provide wider scientific community with instant high-quality NGS which, irrespective publishing laboratory, directly comparable....
Mutations in the parkin gene, which encodes a ubiquitin ligase, are major genetic cause of parkinsonism. Interestingly, also plays role cancer as putative tumor suppressor, and gene is frequently targeted by deletion inactivation human malignant tumors. Here, we investigated potential suppressor for gliomas. We found that expression was dramatically reduced glioma cells. Restoration promoted G(1) phase cell-cycle arrest mitigated proliferation rate cells vitro vivo. Notably,...
Abstract Background The absence of the putative DNA/RNA helicase Schlafen11 (SLFN11) is thought to cause resistance DNA-damaging agents (DDAs) and PARP inhibitors. Methods We developed validated a clinically applicable SLFN11 immunohistochemistry assay retrospectively correlated tumour levels patient outcome standard care therapies olaparib maintenance. Results High associated with improved prognosis first-line treatment DDAs platinum-plus-etoposide in SCLC patients, but was not strongly...
Abstract Purpose: AZD8701 uses next-generation antisense oligonucleotide (ASO) technology to selectively reduce human forkhead box P3 (FOXP3) expression in regulatory T cells, reversing their immunosuppressive function. FOXP3 ASOs alone or with programmed cell death protein (ligand) 1 (PD-[L]1) inhibition attenuated tumor growth mice. We report a phase I study of combined durvalumab patients advanced solid tumors. Methods: Eligible had tumors and received prior standard-of-care treatment...
Combinatorial transcription factor (TF) binding is essential for cell-type-specific gene regulation. However, much remains to be learned about the mechanisms of TF interactions, including what extent constrained spacing and orientation interacting TFs are critical regulatory element activity. To examine relative prevalence 'enhanceosome' versus 'TF collective' model combinatorial binding, a comprehensive analysis site sequences in large scale datasets necessary. We developed motif-pair...
Head and neck squamous cell carcinoma (HNSCC) is a molecularly spatially heterogeneous disease frequently characterized by impairment of immunosurveillance mechanisms. Despite recent success with immunotherapy treatment, progression still occurs quickly after treatment in the majority cases, suggesting need to improve patient selection strategies. In quest for biomarkers that may help inform response checkpoint blockade, we tumor microenvironment (TME) 162 HNSCC primary tumors diverse...
Tertiary Lymphoid Structures (TLS) are lymphoid structures commonly associated with improved survival of cancer patients and response to immunotherapies. However, conflicting reports underscore the need consider TLS heterogeneity multiple features such as size, composition, maturation status, when assessing their functional impact. With aim gaining insights into biology evaluating prognostic impact maturity in Non-Small Cell Lung Carcinoma (NSCLC), we developed a multiplex immunofluorescent...
Integrated analysis of multiple genome-wide transcription factor (TF)-binding profiles will be vital to advance our understanding the global impact TF binding. However, existing methods for measuring similarity in large numbers chromatin immunoprecipitation assays with sequencing (ChIP-seq), such as correlation, mutual information or enrichment analysis, are limited their ability display functionally relevant relationships. In this study, we propose use graphical models determine conditional...
Abstract Cyclin E1 is a key regulator of the G1/S transition and thought to cause excessive entry into cell cycle. CCNE1 amplified in range tumor indications, its amplification associated with poorer prognosis resistance chemotherapy. also being investigated as potential biomarker for inhibitors targeting replication stress response. Understanding best way quantify cyclin overexpression fundamental support patient selection approaches these inhibitors. In many cases, gene correlates...
Genome-wide transcription factor (TF) binding profiles differ dramatically between cell types. However, not much is known about the relationship cell-type-specific patterns and gene expression. A recent study demonstrated how same TFs can have functional roles when to largely non-overlapping genomic regions in hematopoietic progenitor mast cells. Cell-type specific of shared are therefore merely consequence opportunistic functionally irrelevant accessible chromatin, but instead potential...
Neoantigens act as surrogates for T cell immunoreactivity and have been shown to correlate with patients’ response immune checkpoint inhibitors (ICI). Here, we developed a multi-allele convolutional neural network-based model, MINERVA, predicting HLA class I (HLA-I) presentation of tumor antigenic peptides using transfer learning immunopeptidome data from cancer patients. We show that MINERVA recapitulates physicochemical properties naturally presented are relevant biology is more sensitive...
<div>Abstract<p>Mutations in the parkin gene, which encodes a ubiquitin ligase, are major genetic cause of parkinsonism. Interestingly, also plays role cancer as putative tumor suppressor, and gene is frequently targeted by deletion inactivation human malignant tumors. Here, we investigated potential suppressor for gliomas. We found that expression was dramatically reduced glioma cells. Restoration promoted G<sub>1</sub> phase cell-cycle arrest mitigated proliferation...
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