A5065110287- Immunotherapy and Immune Responses
- RNA modifications and cancer
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Medical Imaging Techniques and Applications
- Single-cell and spatial transcriptomics
- Ocular Oncology and Treatments
- Medical and Biological Sciences
- Genomics and Chromatin Dynamics
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Neonatal and fetal brain pathology
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Virus-based gene therapy research
- Neonatal Respiratory Health Research
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- PARP inhibition in cancer therapy
Harry Perkins Institute of Medical Research
2005-2024
The University of Western Australia
2005-2024
The Kids Research Institute Australia
2023-2024
Sahlgrenska University Hospital
2024
University of Gothenburg
2024
ID Genomics (United States)
2024
Queen Elizabeth II Medical Centre
2023
RIKEN Center for Integrative Medical Sciences
2010-2022
Guy's Hospital
2014-2021
Guy's and St Thomas' NHS Foundation Trust
2017-2020
Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets genes has not been previously studied en masse. Exploiting the fact active are transcribed, we simultaneously measured their activity in 19 human 14 mouse time courses covering a wide range cell types biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated earliest responses....
The eukaryotic phylum Apicomplexa encompasses thousands of obligate intracellular parasites humans and animals with immense socio-economic health impacts. We sequenced nuclear genomes Chromera velia Vitrella brassicaformis, free-living non-parasitic photosynthetic algae closely related to apicomplexans. Proteins from key metabolic pathways the endomembrane trafficking systems associated a lifestyle have been progressively non-randomly lost during adaptation parasitism. ancestor contained...
Dendritic cells (DCs) are antigen-presenting controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets not fully understood. Here, we identified circulating CD88−CD1c+CD163+ DCs (called DC3s) as immediate precursors inflammatory CD88−CD14+CD1c+CD163+FcεRI+ DCs. DC3s develop via a specific pathway activated by GM-CSF, independent cDC-restricted (CDP) monocyte-restricted (cMoP) progenitors. Like classical but unlike monocytes, drove activation...
Rationale: Platelets shed microRNAs (miRNAs). Plasma miRNAs change on platelet inhibition. It is unclear whether plasma miRNA levels correlate with function. Objective: To link small RNAs to reactivity. Methods and Results: Next-generation sequencing of in revealed 2 peaks at 22 23 32 33 nucleotides corresponding YRNAs, respectively. Among predominantly, fragments RNY4 RNY5 were detected. YRNAs measured 125 patients a history acute coronary syndrome who had undergone detailed assessment...
Microglia of the developing brain have unique functional properties but how their activation states are regulated is poorly understood. Inflammatory microglia in still-developing preterm-born infants associated with permanent neurological sequelae 9 million every year. Investigating regulators microglial across models neuroinflammation-mediated injury (mouse, zebrafish) and primary human mouse we found using analysis genes proteins that a reduction Wnt/β-catenin signalling necessary...
Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite dramatic recent increase in incidence the aetiopathogenesis FFA remains unknown. We undertake genome-wide association studies females from UK cohort, comprising 844 cases 3,760 controls, Spanish cohort 172 385 perform statistical meta-analysis. observe significant with at four genomic loci: 2p22.2, 6p21.1, 8q24.22 15q2.1. Within 6p21.1 locus,...
Preterm birth places infants in an adverse environment that leads to abnormal brain development and cerebral injury through a poorly understood mechanism known involve neuroinflammation. In this study, we integrate human mouse molecular neuroimaging data investigate the role of microglia preterm white matter damage. Using model where encephalopathy prematurity is induced by systemic interleukin-1β administration, undertake gene network analysis microglial transcriptomic response injury,...
Perivascular adipose tissue (PVAT) plays a vital role in maintaining vascular homeostasis. However, most studies ascribed the function of PVAT remodeling to adipokines secreted by perivascular adipocytes. Whether mesenchymal stem cells exist and play regeneration remain unknown. Approach Results: Single-cell RNA-sequencing allowed direct visualization heterogeneous PVAT-derived (PV-ADSCs) at high resolution revealed 2 distinct subpopulations, among which one featured signaling pathways...
Efficient isolation of specific, intact, living neurons from the adult brain is problematic due to complex nature extracellular matrix consolidating neuronal network. Here, we present significant improvements protocol for pure populations mature postnatal mouse using fluorescence activated cell sorting (FACS). The 10-fold increase in yield enables cell-specific transcriptome analysis by protocols such as nanoCAGE and RNA seq.
Summary Host‐generated oxidative stress is considered one of the main mechanisms constraining Mycobacterium tuberculosis ( Mtb ) growth. The redox‐sensing in are not completely understood. Here we show that WhiB4 responds to oxygen (O 2 and nitric oxide (NO) via its 4Fe‐4S cluster controls response . mutant Δ whiB4 displayed an altered redox balance a reduced membrane potential. Microarray analysis demonstrated overexpresses antioxidant systems including alkyl hydroperoxidase ahpC‐ahpD...
BackgroundRecessive dystrophic epidermolysis bullosa (RDEB) is a hereditary blistering disorder due to lack of type VII collagen. At present, treatment mainly supportive.ObjectivesTo determine whether intravenous allogeneic bone marrow–derived mesenchymal stromal/stem cells (BM-MSCs) are safe in RDEB adults and if the improve wound healing quality life.MethodsWe conducted prospective, phase I/II, open-label study recruiting 10 receive 2 infusions BM-MSCs (on day 0 14; each dose 2-4 × 106...
In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they implicated destruction of insulin-secreting cells. contrast, disease relevance cell–reactive that detectable circulation, and their relationship to function, not known. Here, we tracked multiple, circulating subsets measured function longitudinally 2 years, starting immediately after diagnosis diabetes. We change cell–specific effector memory expressing CD57 was...
Abstract Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to epigenetic derepression of D4Z4 repeats on chromosome 4q, leading ectopic DUX4 expression. FSHD patient myoblasts have defective myogenic differentiation, forming smaller myotubes with reduced myosin content. However, molecular mechanisms driving such disrupted myogenesis in are poorly understood. We performed high-throughput morphological analysis describing and control myogenesis, revealing...
Poly(ADP-ribose) polymerase-1 (PARP-1) is activated by DNA strand breaks during cellular genotoxic stress response and catalyzes poly(ADP-ribosyl)ation of acceptor proteins. These proteins include those involved in modulation chromatin structure, synthesis, repair, transcription, cell cycle control. Thus, PARP-1 believed to play a pivotal role maintaining genome integrity through protein-protein protein-DNA interactions. We previously described the association with normal mammalian...
Poly(ADP-ribose) polymerase 2 (PARP-2) is a newly discovered member of the PARP family. We report association PARP-2 with mammalian centromeres in cell-cycle-dependent manner, accumulating at during prometaphase and metaphase, disassociating anaphase, disappearing from by telophase. Analysis pseudodicentric chromosome human neocentromere indicates that binding occurs only active sequence-independent manner. Centromere peaks outer centromere region, significantly enhanced upon treatment...
The capacity for plasticity in the adult brain is limited by anatomical traces laid down during early postnatal life. Removing certain molecular brakes, such as histone deacetylases (HDACs), has proven to be effective recapitulating juvenile mature visual cortex (V1). We investigated chromatin structure and transcriptional control genome-wide sequencing of DNase I hypersensitive sites (DHSS) cap analysis gene expression (CAGE) libraries after HDAC inhibition valproic acid (VPA) V1. found...