Paola Bonfanti
A5016783896- Tissue Engineering and Regenerative Medicine
- Pancreatic function and diabetes
- SARS-CoV-2 and COVID-19 Research
- Pluripotent Stem Cells Research
- Electrospun Nanofibers in Biomedical Applications
- Tracheal and airway disorders
- Esophageal and GI Pathology
- Diabetes and associated disorders
- Single-cell and spatial transcriptomics
- Myasthenia Gravis and Thymoma
- 3D Printing in Biomedical Research
- T-cell and B-cell Immunology
- interferon and immune responses
- COVID-19 Clinical Research Studies
- Cancer Cells and Metastasis
- Hematopoietic Stem Cell Transplantation
- Neonatal Respiratory Health Research
- Immunotherapy and Immune Responses
- Clinical Nutrition and Gastroenterology
- vaccines and immunoinformatics approaches
- SARS-CoV-2 detection and testing
- Mosquito-borne diseases and control
- Esophageal Cancer Research and Treatment
- Liver physiology and pathology
- Immune Cell Function and Interaction
The Francis Crick Institute
2017-2025
University College London
2016-2025
Centre for Immunity, Infection and Evolution
2022-2025
Institute of Infection and Immunity
2022-2023
Great Ormond Street Hospital
2017-2021
European Institute of Oncology
2021
The Royal Free Hospital
2014-2021
Vrije Universiteit Brussel
2010-2020
KU Leuven
2014
University of Lausanne
2010
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....
Organoids have extensive therapeutic potential and are increasingly opening up new avenues within regenerative medicine. However, their clinical application is greatly limited by the lack of effective GMP-compliant systems for organoid expansion in culture. Here, we envisage that use extracellular matrix (ECM) hydrogels derived from decellularized tissues (DT) can provide an environment capable directing cell growth. These gels possess biochemical signature tissue-specific ECM translation....
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 CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost Barrett’s esophagus (BE) esophageal adenocarcinoma (EAC). How other gene co-deletions affect EAC evolution remains understudied. We explored the effects of loss EACs cancer progressor non-progressor BEs with matched genomic, transcriptomic clinical data. Despite its driver role, BE prevents initiation by counterselecting subsequent TP53 alterations. predict poor patient survival but not through...
A tissue engineered oesophagus could overcome limitations associated with oesophageal substitution. Combining decellularized scaffolds patient-derived cells shows promise for regeneration of defects. In this proof-of-principle study, a two-stage approach generation bio-artificial graft addresses some major challenges in organ engineering, namely: (i) development multi-strata tubular structures, (ii) appropriate re-population/maturation constructs before transplantation, (iii)...
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 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...
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,...
A comparative analysis of mouse and human pancreatic development may reveal common mechanisms that control key steps as organ morphogenesis cell proliferation differentiation. More specifically, understanding beta remains an issue, despite recent progress related to their generation from embryonic induced pluripotent stem cells. In this study, we use integrated approach, including prospective isolation, culture, characterization intermediate stages, report cells fetal pancreas can be...
Abstract Pancreatic endocrine progenitors obtained from human embryonic stem cells (hESCs) represent a promising source to develop cell-based therapies for diabetes. Although pancreas progenitor have been isolated mouse pancreata on the basis of Ngn3 expression, not yet. As substantial differences exist between and murine biology, we investigated whether it is possible isolate pancreatic differentiating hESC cultures by lineage tracing NGN3. We targeted 3′ end NGN3 using zinc finger...
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...
Abstract β-cell replacement has been proposed as an effective treatment for some forms of diabetes, and in vitro methods generation are being extensively explored. A potential source β-cells comes from fate conversion exocrine pancreatic cells into the endocrine lineage, by overexpression three regulators formation identity, Ngn3, Pdx1 MafA. Pancreatic ductal organoid cultures have recently developed that can be expanded indefinitely, while maintaining to differentiate lineage. Here, using...
The formation of hair follicles, a landmark mammals, requires complex mesenchymal-epithelial interactions and it is commonly believed that embryonic epidermal cells are the only can respond to follicle morphogenetic signals in vivo. Here, we demonstrate epithelial stem non-skin origin (e.g. cornea, oesophagus, vagina, bladder, prostate) express transcription factor Tp63, master gene for development epidermis its appendages, skin signals. When exposed newborn microenvironment, these...
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,...