Ilenia Simeoni
A5003703919- Immunodeficiency and Autoimmune Disorders
- Platelet Disorders and Treatments
- Genomics and Rare Diseases
- Ion channel regulation and function
- Blood disorders and treatments
- Renal and related cancers
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- Genetic factors in colorectal cancer
- Pluripotent Stem Cells Research
- Ion Channels and Receptors
- Cystic Fibrosis Research Advances
- Calcium signaling and nucleotide metabolism
- Reproductive Biology and Fertility
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA modifications and cancer
- Retinal Development and Disorders
- Genetics and Neurodevelopmental Disorders
- Telomeres, Telomerase, and Senescence
- Blood groups and transfusion
- Metabolism and Genetic Disorders
- Neuroscience and Neuropharmacology Research
- Medical Imaging and Pathology Studies
- interferon and immune responses
- Lysosomal Storage Disorders Research
Cambridge University Hospitals NHS Foundation Trust
2019-2025
University of Cambridge
2010-2023
National Institute for Health Research
2016-2020
NHS Blood and Transplant
2014-2019
Bridge University
2018
National Health Service
2015-2016
Addenbrooke's Hospital
2011
Wellcome Trust
2007-2011
Wellcome/Cancer Research UK Gurdon Institute
2007-2011
Papworth Hospital
2011
The epigenome refers to marks on the genome, including DNA methylation and histone modifications, that regulate expression of underlying genes. A consistent profile gene changes in end-stage cardiomyopathy led us hypothesize distinct global patterns may also exist.We constructed genome-wide maps histone-3 lysine-36 trimethylation (H3K36me3) enrichment for cardiomyopathic normal human hearts. More than 506 Mb sequences per library were generated by high-throughput sequencing, allowing assign...
E527K hyperactive SRC results in megakaryocytes with increased podosome formation, thrombocytopenia, myelofibrosis, bleeding, and bone pathologies.
Inherited bleeding, thrombotic, and platelet disorders (BTPD) are a heterogeneous set of diseases. The most common inherited bleeding von Willebrand disease (VWD) hemophilia, although all other BTPDs globally very rare, with mostly an unknown prevalence. Over the past five decades, genetic basis some these has been identified. Most genes harboring variants responsible for BTPD have identified through linkage studies across informative pedigrees or using candidate gene Sanger sequencing...
Abstract Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non–self-antigens is an unavoidable adverse side effect transfusion. We describe a universal donor typing platform that could be adopted by services worldwide facilitate extended policy and reduce rates. This DNA-based test capable simultaneously most clinically relevant red cell (RBC), human platelet (HPA), leukocyte (HLA) antigens. Validation was performed, using...
The transcription factor STAT6 (Signal Transducer and Activator of Transcription 6) is a key regulator Th2 (T-helper 2) mediated allergic inflammation via the IL-4 (interleukin-4) JAK (Janus kinase)/STAT signalling pathway. We identified novel heterozygous germline mutation c.1255G > C, p.D419H leading to overactivity JAK/STAT pathway, in kindred affected by early-onset atopic dermatitis, food allergy, eosinophilic asthma, anaphylaxis follicular lymphoma. D419H expression functional activity...
Carnitine is a physiological cellular constituent that favors intracellular fatty acid transport, whose role on platelet function and O(2) free radicals has not been fully investigated. The aim of this study was to seek whether carnitine interferes with arachidonic metabolism function. (10-50 microM) able dose dependently inhibit incorporation into phospholipids agonist-induced release. Incubation platelets inhibited collagen-induced aggregation, thromboxane A(2) formation, Ca(2+)...
Full-grown Xenopus oocytes in first meiotic prophase contain an immensely enlarged nucleus, the Germinal Vesicle (GV), that can be injected with several hundred somatic cell nuclei. When nuclei of mammalian cells or cultured lines are into a GV, wide range genes not transcribed donor cells, including pluripotency genes, start to transcriptionally activated, and synthesize primary transcripts continuously for days. Because large size abundance laevis oocytes, this experimental system offers...
Tumor necrosis factor receptor–associated 3 (TRAF3) is a central regulator of immunity. TRAF3 often somatically mutated in B cell malignancies, but its role human immunity not defined. Here, five unrelated families, we describe an immune dysregulation syndrome recurrent bacterial infections, autoimmunity, systemic inflammation, lymphoproliferation, and hypergammaglobulinemia. Affected individuals each had monoallelic mutations that reduced expression. Immunophenotyping showed patients’ cells...
Significance Next-generation sequencing is identifying millions of novel gene variants, presenting challenges to researchers and clinicians. Variations in the genes ITGA2B ITGB3 affect integrin αIIbβ3, leading bleeding disorder Glanzmann thrombasthenia. We analyzed missense variants on ∼32,000 alleles found affecting ∼10% amino acids each protein ∼1.3% population. Almost all are rare, indicating recent entry into Two we predicted would be deleterious profoundly affected recombinant...
The heterogeneous manifestations of MYH9-related disorder (MYH9-RD), characterized by macrothrombocytopenia, Döhle-like inclusion bodies in leukocytes, bleeding variable severity with, some cases, ear, eye, kidney, and liver involvement, make the diagnosis for these patients still challenging clinical practice. We collected phenotypic data analyzed genetic variants more than 3,000 with a or platelet disorder. Patients were enrolled BRIDGE-BPD ThromboGenomics Projects their samples processed...
Ryanodine receptors (RyRs) are expressed on the endoplasmic reticulum of many cells, where they form intracellular Ca2+-release channels that participate in generation Ca2+ signals. Here we report studies localisation and functional properties transfected RyR1 or RyR3 HEK 293 cells. Immunofluorescence indicated both did not clusters but were homogeneously distributed throughout reticulum. release experiments showed responded to caffeine, although with different sensitivity,generating a...
Amphibian oocytes have the special ability to directly induce transcription of pluripotency and other genes in transplanted somatic nuclei. To this extent, a stem cell-like pattern cell We ask whether induced nuclei reflects normal transcriptional activity oocyte genes. describe here transcript content wide range Xenopus tropicalis oocytes. Using accurate quantitation, we find that each mature has accumulated several hundred transcripts cell-type specific This value is orders magnitude...
Transplantation into eggs or oocytes is an effective means of achieving the reprogramming somatic cell nuclei. We ask here whether provision gene-specific transcription factors forms part mechanism by which a gene that repressed in cells transcribed oocytes. find M1 have extremely strong transcription-inducing activity. They cause muscle genes nuclei from non-muscle cells, after injection oocytes, to be nearly same extent as cells. show, surprisingly, myogenic factor MyoD and other known are...