A5002836016- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Treatments and Mutations
- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- Single-cell and spatial transcriptomics
- Tuberculosis Research and Epidemiology
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- Extracellular vesicles in disease
- Immune cells in cancer
- interferon and immune responses
- Lung Cancer Research Studies
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- Cancer Research and Treatments
- Hippo pathway signaling and YAP/TAZ
- Metastasis and carcinoma case studies
- Mycobacterium research and diagnosis
- Helicobacter pylori-related gastroenterology studies
- CAR-T cell therapy research
- Advanced biosensing and bioanalysis techniques
AstraZeneca (Brazil)
2025
AstraZeneca (United Kingdom)
2021-2024
Wellcome Sanger Institute
2015-2021
University of Minho
2015-2019
European Bioinformatics Institute
2014-2018
Wellcome Trust
2018
The assay for transposase-accessible chromatin using sequencing (ATAC-seq) is widely used to identify regulatory regions throughout the genome. However, very few studies have been performed at single cell level (scATAC-seq) due technical challenges. Here we developed a simple and robust plate-based scATAC-seq method, combining upfront bulk Tn5 tagging with single-nuclei sorting. We demonstrate that our method works robustly across various systems, including fresh cryopreserved cells from...
Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4+ regulatory (Treg) memory (Tmem) T in mouse skin colon, their respective draining lymph nodes (LNs) spleen. In these tissues, we identified Treg cell subpopulations distinct degrees NLT phenotype. Subpopulation pseudotime ordering gene kinetics were consistent recruitment yet the initial NLT-priming LNs final stages...
The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for delivery such an atlas. However, delays between fresh sample collection and processing may lead poor difficulties in experimental design.This study assesses effect cold storage on healthy spleen, esophagus, lung from ≥ 5 donors over 72 h. We collect 240,000 single-cell transcriptomes with detailed type annotations whole...
T helper type 2 (Th2) cells are important regulators of mammalian adaptive immunity and have relevance for infection, autoimmunity, tumor immunology. Using a newly developed, genome-wide retroviral CRISPR knockout (KO) library, combined with RNA-seq, ATAC-seq, ChIP-seq, we dissected the regulatory circuitry governing activation differentiation these cells. Our experiments distinguish cell versus in quantitative framework. We demonstrate that two processes tightly coupled jointly controlled...
Mutations in the STK11 (LKB1) gene regulate resistance to PD-1/PD-L1 blockade. This study evaluated this association patients with nonsquamous non-small cell lung cancer (NSCLC) enrolled three phase I/II trials. mutations were associated anti-PD-L1 antibody durvalumab (alone/with anti-CTLA4 tremelimumab) independently of KRAS mutational status, highlighting as a potential driver checkpoint Retrospective assessments tumor tissue, whole blood, and serum revealed unique immune phenotype...
Abstract Oral selective estrogen receptor degraders (SERD) could become the backbone of endocrine therapy (ET) for receptor–positive (ER+) breast cancer, as they achieve greater inhibition ER-driven cancers than current ETs and overcome key resistance mechanisms. In this study, we evaluated preclinical pharmacology efficacy next-generation oral SERD camizestrant (AZD9833) assessed ER–co-targeting strategies by combining with CDK4/6 inhibitors (CDK4/6i) PI3K/AKT/mTOR-targeted in models...
Abstract The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit melanoma lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent treatment mouse tumor models reveals CD8 + T-cell dependent antitumor activity, which is separate from effects cells. Ceralasertib suppresses proliferating T-cells rapidly reversed off-treatment. causes up-regulation...
Most lung cancer patients with metastatic eventually relapse drug-resistant disease following treatment and EGFR mutant is no exception. Genome-wide CRISPR screens, to either knock out or overexpress all protein-coding genes in cell lines, revealed the landscape of pathways that cause resistance inhibitors osimertinib gefitinib cancer. Among most recurrent were those regulate Hippo pathway. Following a subpopulation cells are able survive over time develop stable resistance. These...
Abstract The crucial capability of T cells for discrimination between self and non-self peptides is based on negative selection developing thymocytes by medullary thymic epithelial (mTECs). mTECs purge autoreactive expression cell-type specific genes referred to as tissue-restricted antigens (TRAs). Although the autoimmune regulator (AIRE) protein known promote a subset TRAs, its mechanism action still not fully understood. TRAs that are under control AIRE also needs further...
Transcriptomics supports that human T reg cells differentiate into mature lymphoid tissue or circulating follicular regulatory cells.
Abstract High-throughput single cell RNA sequencing (scRNA-seq) has become an established and powerful method to investigate transcriptomic cell-to-cell variation, revealed new types, insights into developmental process stochasticity in gene expression. There are now several published scRNA-seq protocols, which all sequence transcriptomes from a minute amount of starting material. Therefore, key question is how these methods compare terms sensitivity detection mRNA molecules, accuracy...
Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, an irreversible EGFR-TKI, are important treatments for non-small cell lung cancer with EGFR-TKI sensitizing or T790M resistance mutations. While patients treated osimertinib show clinical benefit, disease progression and drug common. Emergence of de novo acquired from a tolerant persister (DTP) population is one mechanism proposed to explain on other targeted therapies. Here we profiled DTPs using RNA-seq...
Advancements in single-cell technologies and deep sequencing have revealed the vast B-cell repertoire arising from immunisation, enhancing number of antibodies available for testing. However, selecting highest affinity many sequences is not a straightforward feat, as mechanisms sustaining maturation related markers remain under-studied. Here, we generated datasets antigen-specific B-cells after mouse immunisation well re-analysed public data to identify novel transcriptomic signature, "High...
Summary Non-lymphoid tissues (NLTs) harbour a pool of adaptive immune cells, the development and phenotype which remains largely unexplored. Here, we used single-cell RNA-seq to characterise CD4 + regulatory (Treg) memory (Tmem) T cells in mouse skin colon, respective draining lymph nodes spleen. From this data, modelled continuous lymphoid-to-NLT trajectory for Treg, reconstructed mechanisms cell migration NLT adaption. This revealed shared transcriptional programme priming both...
Summary As the first line of defence against pathogens, cells mount an innate immune response, which is highly variable from cell to cell. The response must be potent yet carefully controlled avoid self-damage. How these constraints have shaped evolution immunity remains poorly understood. Here, we characterise this programme’s transcriptional divergence between species and expression variability across cells. Using bulk single-cell transcriptomics in primate rodent fibroblasts challenged...
Abstract Background The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single RNA sequencing can generate high quality data for delivery such an atlas. However, delays between fresh sample collection and processing may lead poor difficulties in experimental design. Despite this, there has not yet been systematic assessment effect cold storage time on scRNAseq Results This study assessed healthy spleen, oesophagus lung from ≥5 donors...
Abstract The assay for transposase-accessible chromatin using sequencing (ATAC-seq) is widely used to identify regulatory regions throughout the genome. However, very few studies have been performed at single cell level (scATAC-seq) due technical challenges. Here we developed a simple and robust plate-based scATAC-seq method, combining upfront bulk Tn5 tagging with single-nuclei sorting. We demonstrated that our method worked robustly across various systems, including fresh cryopreserved...
Abstract T helper type 2 (Th2) cells are important regulators of mammalian adaptive immunity and have relevance for infection, auto-immunity tumour immunology. Using a newly developed, genome-wide retroviral CRISPR knock-out (KO) library, combined with RNA-seq, ATAC-seq ChIP-seq, we dissected the regulatory circuitry governing activation (including proliferation) differentiation these cells. Our experiments distinguish cell versus in quantitative framework. We demonstrate that two processes...