A5078085305- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- 3D Printing in Biomedical Research
- Genomics and Chromatin Dynamics
- Animal Genetics and Reproduction
- Immunotherapy and Immune Responses
- Genomic variations and chromosomal abnormalities
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- Renal and related cancers
- Biomedical Ethics and Regulation
- Cancer Genomics and Diagnostics
- Prenatal Screening and Diagnostics
- Cell Adhesion Molecules Research
- Digestive system and related health
- Diabetes and associated disorders
- DNA and Nucleic Acid Chemistry
- Hemoglobinopathies and Related Disorders
- Mitochondrial Function and Pathology
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Cytomegalovirus and herpesvirus research
University of Copenhagen
2021-2024
University of Sheffield
2017-2023
Anthony Nolan
2012-2017
The Royal Free Hospital
2012-2014
University College London
2012-2014
Stanford University
2012
European Bioinformatics Institute
2012
Wellcome Trust
2012
The Immuno Polymorphism Database (IPD) was developed to provide a centralized system for the study of polymorphism in genes immune system. Through IPD project we have established central platform curation and publication locus-specific databases involved either directly or related function Major Histocompatibility Complex number different species. We collaborated with specialist groups nomenclature committees that curate individual sections before they are submitted online publication....
It is 14 years since the IMGT/HLA database was first released, providing HLA community with a searchable repository of highly curated sequences. The complex located within 6p21.3 region human chromosome 6 and contains more than 220 genes diverse function. Of these, 21 encode proteins immune system that are polymorphic. naming these alleles their quality control responsibility World Health Organization Nomenclature Committee for Factors System. Through work Informatics Group in collaboration...
The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study polymorphic genes in immune system. IPD project works with groups or nomenclature committees who provide and curate individual sections before they are submitted for online publication. stores all data databases. currently consists four databases: IPD-KIR, contains allelic sequences killer-cell immunoglobulin-like receptors, IPD-MHC, database major histocompatibility...
Human pluripotent stem cells (PSCs) are subject to the appearance of recurrent genetic variants on prolonged culture. We have now found that, compared with isogenic differentiated cells, PSCs exhibit evidence considerably more DNA damage during S phase cell cycle, apparently as a consequence replication stress marked by slower progression replication, activation latent origins and collapse forks. As in many cancers, which, like PSCs, shortened G1 stress, resulting may underlie higher...
The timing of DNA replication in mammals is crucial for minimizing errors and influenced by genome usage chromatin states. Replication the newly formed mammalian embryo remains poorly understood. Here, we have investigated mouse zygotes 2-cell embryos, revealing that lack a conventional program, which then emerges embryos. This program differs from embryonic stem cells generally correlates with transcription compartmentalization both parental genomes. However, consistent systematic...
Abstract We postulate that exit from pluripotency involves intermediates retain while simultaneously exhibiting lineage-bias. Using a MIXL1 reporter, we explore mesoderm lineage-bias within the human pluripotent stem cell compartment. identify substate, which at single level coexpresses and mesodermal gene expression programmes. Functionally these cells initiate cultures exhibit bias in differentiation assays. By promoting identity through manipulation of WNT signalling preventing using...
Abstract Human pluripotent stem cells (PSC) acquire recurrent chromosomal instabilities during prolonged in vitro culture that threaten to preclude their use cell‐based regenerative medicine. The rapid proliferation of leads constitutive replication stress, hindering the progression DNA forks and some cases leading replication‐fork collapse. Failure overcome stress can result incomplete genome duplication, which, if left persist into subsequent mitosis, structural numerical instability. We...
Human stem cells have the potential to transform medicine. However, hurdles remain ensure that manufacturing processes produce safe and effective products. A thorough understanding of biological occurring during manufacture is fundamental assuring these qualities thus, their acceptability regulators clinicians. Leaders in both human pluripotent somatic cells, were brought together with experts clinical translation, biomanufacturing regulation, discuss key issues appropriate conditions for...
Abstract Human pluripotent stem cells (hPSCs) are prone to acquiring genetic changes upon prolonged culture. Particularly common copy number changes, including gains of chromosomes 1q, 12p, 17q, and 20q, and/or loss 10p 18q. The variant harboring display altered behaviors compared their diploid counterparts, thus potentially impacting the validity experimental results safety hPSC‐derived cellular therapies. Hence, a critical quality attribute in hPSC maintenance should include frequent...
Abstract Human pluripotent stem cells (hPSCs) can be grown in culture indefinitely, making them a valuable tool for use basic biology, disease modeling, and regenerative medicine. However, over prolonged periods culture, hPSCs tend to acquire genomic aberrations that confer growth advantages, similar those seen some cancers. Monitoring the stability of cultured is critical ensuring their efficacy safety as therapeutic tool. Most commonly employed methods monitoring hPSC genomes are...
Abstract In this article, we describe a subgroup‐specific amplification assay for HLA‐DQA1 that encompasses the whole coding region and allows us to sequence full‐length genes. We introduce novel alleles HLA‐ DQA1 * 01:10 01:11 . Moreover, were able confirm genomic data of 01:07 , 03:01:01 03:02 04:01:02 04:02 05:03 05:05:01:02 06:01:01 A complete overview all six allele groups is now available from submission our IMGT / HLA database. Because approach facilitates analysis sequences, may...
Human pluripotent stem cells (hPSCs) are a promising source of somatic for clinical applications and disease modelling. However, during culture they accumulate genetic aberrations such as amplification 20q11.21 which occurs in approximately 20% extensively cultured hPSC lines confers BCL2L1-mediated survival advantage. During the production large number required transplantation therapy these may become unavoidable has important safety implications therapies also impact upon Presently, risks...
The new DRB1*11:129 allele differs from the closest matching HLA‐DRB1*11:06:01 by one nucleotide substitution in exon 3 at position 623 (G→A).
Copy number variants (CNVs) are genomic rearrangements implicated in numerous congenital and acquired diseases, including cancer. The appearance of culture-acquired CNVs human pluripotent stem cells (PSCs) has prompted concerns for their use regenerative medicine. A particular problem PSC is the frequent occurrence q11.21 region chromosome 20. However, exact mechanism origin this amplicon remains elusive due to difficulty delineating its sequence breakpoints. Here, we have addressed using...
HLA-DRB1*03:85 differs from HLA-DRB1*03:06 by two nucleotides, position 257 A>T and 258T>C, resulting in Valine at codon 57.
Abstract The timing of mammalian DNA replication is crucial for minimizing errors and influenced locally by genome usage chromatin states. However, our understanding in the unique environment that exists newly formed embryos limited. Here, we performed genome-wide investigations mouse zygotes 2-cell embryos. We discovered lack a conventional timing, but program emerged Notably, this differs from embryonic stem cells shows asynchrony between parental genomes. observed late maternal...
Human pluripotent stem cells (PSC) often acquire genetic changes on prolonged culture, which pose concerns for their use in research and regenerative medicine (Amps et al., 2011, Seth 2011). The acquisition of these during culture necessarily first requires mutation then selection those mutations that provide a growth advantage. Whilst accounts the recurrent nature variants commonly reported (Draper 2004, Olariu 2010), mechanisms PSC remain largely elusive. Here we show that, contrast to...
The HFE molecule controls iron uptake from gut, and defects in the have been associated with overload, particularly hereditary hemochromatosis. gene including both coding boundary intronic regions were sequenced 304 Brazilian individuals, encompassing healthy individuals patients exhibiting or acquired overload. Six sites of variation detected: (1) H63D C>G exon 2, (2) IVS2 (+4) T>C intron (3) a transversion 3, (4) C282Y G>A 4, (5) IVS4 (−44) (6) new guanine deletion (G>del) 5,...
ABSTRACT We postulate that exit from pluripotency involves intermediates retain while simultaneously exhibiting lineage-bias. Using a MIXL1 reporter, we explored mesoderm lineage-bias within the human pluripotent stem cell compartment. identified substate, which at single level coexpresses and mesodermal gene expression programs. Functionally these cells could initiate cultures exhibited bias in differentiation assays. By promoting identity through manipulation of WNT signalling preventing...
Abstract Copy number variants (CNVs) are genomic rearrangements implicated in numerous congenital and acquired diseases, including cancer. In human pluripotent stem cells (PSC), the appearance of culture-acquired CNVs prompted concerns for their use regenerative medicine applications. A particularly common problem PSC is occurrence q11.21 region chromosome 20. However, exact mechanisms origin this amplicon remains elusive due to difficulty delineating its sequence breakpoints. Here, we used...