Roberta Ragazzini
A5088032764- SARS-CoV-2 and COVID-19 Research
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- COVID-19 Clinical Research Studies
- interferon and immune responses
- Myasthenia Gravis and Thymoma
- T-cell and B-cell Immunology
- Hematopoietic Stem Cell Transplantation
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- Cancer-related gene regulation
- Mosquito-borne diseases and control
- Cancer-related molecular mechanisms research
- Lymphatic System and Diseases
- Acute Myeloid Leukemia Research
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- Cancer therapeutics and mechanisms
- Childhood Cancer Survivors' Quality of Life
- Diabetes and associated disorders
- melanin and skin pigmentation
The Francis Crick Institute
2020-2024
Centre for Immunity, Infection and Evolution
2022-2024
University College London
2020-2024
Institute of Infection and Immunity
2023
The Royal Free Hospital
2021
Great Ormond Street Hospital
2020
Laboratoire de Biologie du Développement
2019
Institut Curie
2017-2019
Génétique et biologie du développement
2019
Université Paris Sciences et Lettres
2017-2019
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 emergence of SARS-CoV-2 variants concern suggests viral adaptation to enhance human-to-human transmission
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human adaptation resulted in distinct lineages with enhanced transmissibility called variants of concern (VOCs). Omicron is the first VOC to evolve globally dominant subvariants. Here we compared their replication cell lines and primary airway cultures measured host responses infection. We discovered that subvariants BA.4 BA.5 have improved suppression innate immunity when earlier BA.1 BA.2. Similarly, more recent (BA.2.75...
Abstract Long non‐coding RNA s (lnc s) play diverse roles in physiological and pathological processes. Several lnc have been suggested to modulate gene expression by guiding chromatin‐modifying complexes specific sites the genome. However, besides example of Xist, clear‐cut evidence demonstrating this novel mode regulation remains sparse. Here, we focus on HOTAIR , a that is overexpressed several tumor types previously proposed key role silencing through direct recruitment Polycomb...
Abstract The Polycomb group of proteins is required for the proper orchestration gene expression due to its role in maintaining transcriptional silencing. It composed several chromatin modifying complexes, including Repressive Complex 2 (PRC2), which deposits H3K27me2/3. Here, we report identification a cofactor PRC2, EZHIP (EZH1/2 Inhibitory Protein), expressed predominantly gonads. limits enzymatic activity PRC2 and lessens interaction between core complex accessory subunits, but does not...
Abstract The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning generation the potential to manipulate it clinically, because alterations of development or function can result severe immunodeficiency autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable long-term expansion vitro, able reconstitute an anatomic phenocopy native thymus, when combined with thymic interstitial...
SARS-CoV-2 spike requires proteolytic processing for viral entry. A polybasic furin-cleavage site (FCS) in spike, and evolution toward an optimized FCS by dominant variants of concern (VOCs), are linked to enhanced infectivity transmission. Here we show interferon-inducible restriction factors Guanylate-binding proteins (GBP) 2 5 interfere with furin-mediated cleavage inhibit the early-lineage isolates Wuhan-Hu-1 VIC. By contrast, VOCs Alpha Delta escape GBP2/5 that map substitution D614G...
Thymus is necessary for lifelong immunological tolerance and immunity. It displays a distinctive epithelial complexity undergoes age-dependent atrophy. Nonetheless, it also retains regenerative capacity, which, if harnessed appropriately, might permit rejuvenation of adaptive By characterizing cortical medullary compartments in the human thymus at single-cell resolution, this study we have defined specific populations, including those that share properties with bona fide stem cells (SCs)...
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,...
ABSTRACT A series of SARS-CoV-2 variants concern (VOCs) have evolved in humans during the COVID-19 pandemic—Alpha, Beta, Gamma, Delta, and Omicron. Here, we used global proteomic genomic analyses infection to understand molecular responses driving VOC evolution. We discovered VOC-specific differences viral RNA protein expression levels, including for N, Orf6, Orf9b, pinpointed several mutations responsible. An analysis host response comprehensive interrogation altered virus-host...
SARS-CoV-2 adaptation to humans is evidenced by the emergence of variants concern (VOCs) with distinct genotypes and phenotypes that facilitate immune escape enhance transmission frequency. Most recently Omicron subvariants have emerged heavily mutated spike proteins which re-infection populations through extensive antibody driving replacement previously-dominant VOCs Alpha Delta. Interestingly, first VOC produce subvariants. Here, we demonstrate later subvariants, particularly BA.4 BA.5,...
Abstract The human thymus is the site of T‐cell maturation and induction central tolerance. Hematopoietic stem cell (HSC)‐derived progenitors are recruited to from fetal liver during early prenatal development bone marrow at later stages postnatal life. mechanism by which HSCs poorly understood in humans, though mouse models have indicated critical role thymic stromal cells (TSC). Here, we developed a 3D microfluidic assay based on model HSC extravasation across endothelium into...
Abstract Background The thymus, responsible for T cell-mediated adaptive immune system, has a structural and functional complexity that is not yet fully understood. Until now, thymic anatomy been studied using histological thin sections or confocal microscopy 3D reconstruction, necessarily limited volumes. Methods We used Phase Contrast X-Ray Computed Tomography to address the lack of whole-organ volumetric information on microarchitecture its components. scanned 15 human thymi (9 foetal 6...
More transmissible SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used global proteomic and genomic approaches to study host responses driving VOC evolution. We discovered VOCs evolved convergent strategies remodel response by modulating viral RNA protein levels, altering nucleocapsid phosphorylation, rewiring virus-host protein-protein interactions. Integrative systems analysis revealed that although Alpha, Beta, Gamma, Delta ultimately converged in...
<title>Abstract</title> Thymic involution is an age-related process that results in reduced T cell production and impaired adaptive immunity. However, it remains uncertain the extent of thymic activity later life how this contributes to immunological ageing. Here, we identified tissue within mediastinal adipose locations aged individuals confirmed its functional capacity through multi-omics analysis. Percentage CD31+ CD4+ cells correlated positively with presence. output elderly showed a...
Thymus is considered a non-functional remnant in adults, but some evidence suggest that it may harbor residual activity. Lung cancer patients represent the ideal model to study thymic activity, as their thymus can be easily harvested during surgery. This was designed confirm presence of activity both adult mice (step 1) and humans 2). In step 1, lung induced by activating k-ras mutation cohort 20 young mice. After killing, lungs were analyzed. active when medullary evident, cortico-medullary...
ABSTRACT Nasopharyngeal colonisation by Streptococcus pneumoniae is characterised adherence to epithelial cells, microinvasion and an innate immune response. Here, we explore the hypothesis that pneumococcal virulence has primarily evolved promote these processes subsequent transmission, rather than cause disease. We have used a S. serotype 6B strain, alongside two biosynthesis gene mutants ( ΔproABC Δfhs with additional ΔpiaA mutation) known colonise murine human models without causing show...
ABSTRACT The Polycomb machinery is required for the proper orchestration of gene expression by virtue its critical role in maintaining transcriptional silencing. It composed several chromatin modifying complexes, including Repressive Complex 2 (PRC2), which deposits H3K27me2/3. Here, we report identification a new cofactor PRC2, EZHIP (EZH1/2 Inhibitory Protein), expressed predominantly gonads. limits enzymatic activity PRC2 and lessens interaction between core complex accessory subunits,...