A5034389766- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Organ Transplantation Techniques and Outcomes
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Renal Transplantation Outcomes and Treatments
- Renal cell carcinoma treatment
- Transplantation: Methods and Outcomes
- COVID-19 Clinical Research Studies
- Renal and related cancers
- Immunodeficiency and Autoimmune Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Liver Disease and Transplantation
- SARS-CoV-2 detection and testing
- Immune cells in cancer
- Systemic Lupus Erythematosus Research
- Renal and Vascular Pathologies
- Gut microbiota and health
- Extracellular vesicles in disease
- Cancer Immunotherapy and Biomarkers
- Lymphoma Diagnosis and Treatment
University of Cambridge
2017-2025
MRC Laboratory of Molecular Biology
2018-2024
Medical Research Council
2020-2023
Charles River Laboratories (United Kingdom)
2021-2022
Boston Biomedical (United States)
2022
NHS Blood and Transplant
2021
National Institute for Health Research
2021
National Institutes of Health
2014-2018
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2014-2018
University of Southampton
2011-2018
Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines identities malignant cells diversity tumor tissue. We studied 72,501 single-cell transcriptomes renal tumors normal tissue from fetal, pediatric, adult kidneys. matched childhood Wilms with specific fetal cell types, thus providing evidence for hypothesis that are aberrant cells. carcinoma, we identified a canonical cancer transcriptome little-known subtype proximal convoluted tubular cell....
Thymus development, cell by The human thymus is the organ responsible for maturation of many types T cells, which are immune cells that protect us from infection. However, it not well known how these develop with a full complement contains necessary variation to variety pathogens. By performing single-cell RNA sequencing on more than 250,000 Park et al. examined changes occur in over course life. They found development occurs coordinated manner among and their developmental microenvironment....
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...
Immune landscape of the human kidney Single-cell RNA sequencing has begun to shed light on full cellular diversity specific organs. However, these studies rarely examine organ-specific immune cells. Stewart et al. sequenced healthy adult and fetal samples at a single-cell level define heterogeneity in epithelial, myeloid, lymphoid From this dataset, they identified zonation cells, with relevance disease varied perturbations that occur different tumor settings. This profiling generates...
IgG antibodies cause inflammation and organ damage in autoimmune diseases such as systemic lupus erythematosus (SLE). We investigated the metabolic profile of macrophages isolated from inflamed tissues immune complex (IC)-associated diseases, including SLE rheumatoid arthritis, following Fcγ receptor cross-linking. found that human mouse undergo a switch to glycolysis response IC stimulation, mirroring macrophage changes tissue vivo. This reprogramming was required generate number...
Tumor behavior is intricately dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. To understand these dependencies within wider microenvironment, we studied over 270,000 single-cell transcriptomes 100 microdissected whole exomes from 12 patients with kidney tumors, prior to validation using spatial transcriptomics. Tissues were sampled multiple regions tumor core, tumor-normal interface, normal surrounding tissues, peripheral blood. We find that...
Improving the efficacy of immune checkpoint therapies will require a better understanding how cells are recruited and sustained in tumors. Here, we used photoconversion tumor cell compartment to identify newly entering lymphocytes, determine they change over time, investigate their egress from tumor. Combining single-cell transcriptomics flow cytometry, found that while diverse mix CD8 T subsets enter tumor, all retained within this environment for more than 72 h developed an exhausted...
Macrophages play a central role in intestinal immunity, but inappropriate macrophage activation is associated with inflammatory bowel disease (IBD). Here, we identify granulocyte-macrophage colony stimulating factor (GM-CSF) as critical regulator of patients IBD and mice dextran sodium sulfate (DSS)-induced colitis. We find that GM-CSF drives the maturation polarization macrophages, promoting anti-microbial functions while suppressing wound-healing transcriptional programs. Group 3 innate...
Abstract The TNF family cytokine TL1A (Tnfsf15) costimulates T cells and type 2 innate lymphocytes (ILC2) through its receptor DR3 (Tnfrsf25). DR3-deficient mice have reduced cell accumulation at the site of inflammation ILC2-dependent immune responses in a number models autoimmune allergic diseases. In lung disease models, immunopathology local Th2 ILC2 is despite normal systemic priming generation secreting IL-13 IL-4, prompting question whether promotes development other subsets that...
Background and Aims Organoids provide a powerful system to study epithelia in vitro . Recently, this approach was applied successfully the biliary tree, series of ductular tissues responsible for drainage bile pancreatic secretions. More precisely, organoids have been derived from ductal tissue located outside (extrahepatic ducts; EHBDs) or inside liver (intrahepatic IHBDs). These share many characteristics, including expression cholangiocyte markers such as keratin (KRT) 19. However,...
B cells play a central role in humoral immunity but also have antibody-independent functions. Studies to date focused on blood and secondary lymphoid organs whether reside non-lymphoid (NLO) homeostasis is unknown. Here we identify, using intravenous labeling parabiosis, bona-fide tissue-resident cell population lung, liver, kidney urinary bladder, substantial proportion of which are B-1a cells. Tissue-resident present neonatal tissues germ-free mice NLOs, albeit lower numbers than specific...
Transplantation is the optimal treatment for most patients with end-stage kidney disease but organ shortage a major challenge. Normothermic machine perfusion (NMP) has been used to recondition marginal organs; however, mechanisms by which NMP might benefit organs are not well understood. Using pairs of human kidneys obtained from same donor, we compared effect that cold storage on global transcriptome. We found led reduction in gene expression, including inflammatory pathway genes and those...
Abstract The thymus provides a nurturing environment for the differentiation and selection of T cells, process orchestrated by their interaction with multiple thymic cell types. We utilised single-cell RNA-sequencing (scRNA-seq) to create census human reconstruct T-cell trajectories receptor (TCR) recombination kinetics. Using this approach, we identified located in situ novel CD8αα + populations, fibroblast subtypes activated dendritic (aDC) states. In addition, reveal bias TCR selection,...
Thousands of kidneys from higher-risk donors are discarded annually because the increased likelihood complications posttransplant. Given severe organ shortage, there is a critical need to improve utilization these organs. To this end, normothermic machine perfusion (NMP) has emerged as platform for ex vivo assessment and potential repair marginal In recent study 8 transplant-declined human on NMP, we discovered microvascular obstructions that impaired blood flow. However, nature physiologic...
Abstract Infection or vaccination leads to the development of germinal centers (GC) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma memory cells. Here we follow migratory pathways emerging from (B EM ) and find that many migrate into lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From SCS, may exit enter distant tissues, while some interact with take up SCS macrophages, followed CCL21-guided return towards GC....