A5021904108- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Erythrocyte Function and Pathophysiology
- RNA modifications and cancer
- Acute Myeloid Leukemia Research
- Hemoglobinopathies and Related Disorders
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Animal Genetics and Reproduction
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Prenatal Screening and Diagnostics
- Telomeres, Telomerase, and Senescence
- Genetic Mapping and Diversity in Plants and Animals
- Chronic Lymphocytic Leukemia Research
- Genomics and Phylogenetic Studies
- Muscle Physiology and Disorders
- Blood groups and transfusion
- Cancer-related gene regulation
University of Oxford
2012-2024
MRC Weatherall Institute of Molecular Medicine
2012-2024
John Radcliffe Hospital
2007-2022
Institute for Molecular Medicine
2021
Medical Research Council
1999-2018
Great Ormond Street Hospital
2008
Candiolo Cancer Institute
2008
Institute of Cancer Research
2008
University College London
2008
Aichi Cancer Center
2008
Understanding cancer pathogenesis requires knowledge of not only the specific contributory genetic mutations but also cellular framework in which they arise and function. Here we explore clonal evolution a form childhood precursor–B cell acute lymphoblastic leukemia that is characterized by chromosomal translocation generating TEL-AML1 fusion gene. We identify compartment leukemic children can propagate when transplanted mice. By studying monochorionic twin pair, one preleukemic with frank...
Advanced FIB-SEM and 3D-SIM imaging uncover cohesin-independent chromatin arrangement into structural functional modules.
We describe a pathogenetic mechanism underlying variant form of the inherited blood disorder α thalassemia. Association studies affected individuals from Melanesia localized disease trait to telomeric region human chromosome 16, which includes α-globin gene cluster, but no molecular defects were detected by conventional approaches. After resequencing and using combination chromatin immunoprecipitation expression analysis on tiled oligonucleotide array, we identified gain-of-function...
Genes on different chromosomes can be spatially associated in the nucleus several transcriptional and regulatory situations; however, functional significance of such associations remains unclear. Using human erythropoiesis as a model, we show that five cotranscribed genes, which are found four chromosomes, associate with each other at significant but variable frequencies. Those genes most frequently association lie decondensed stretches chromatin. By replacing mouse α-globin gene cluster...
ATRX is a member of the SNF2 family helicase/ATPases that thought to regulate gene expression via an effect on chromatin structure and/or function. Mutations in hATRX cause severe syndromal mental retardation associated with α-thalassemia. Using indirect immunofluorescence and confocal microscopy we have shown protein pericentromeric heterochromatin during interphase mitosis. By coimmunofluorescence, localizes mouse homologue Drosophila heterochromatic HP1 vivo , consistent previous...
The organization of genes within the nucleus may influence transcription. We have analyzed nuclear positioning coordinately regulated α- and β-globin show that gene-dense chromatin surrounding human α-globin is frequently decondensed, independent Against this background, we frequent juxtaposition active homologous loci occurs at speckles correlates with However, did not see increased colocalization signals, which would be expected direct physical interaction. same degree proximity does occur...
The three-dimensional (3D) organization of chromosomes can be probed using methods like Capture-C. However, it is unclear how such population-level data relate to the within a single cell, and mechanisms leading observed interactions are still largely obscure. We present polymer modeling scheme based on assumption that chromosome architecture maintained by protein bridges, which form chromatin loops. To test model, we perform FISH experiments compare with Capture-C data. Starting merely from...
Abstract Mammalian gene expression patterns are controlled by regulatory elements, which interact within topologically associating domains (TADs). The relationship between activation of formation structural chromatin interactions and during development is unclear. Here, we present Tiled-C, a low-input chromosome conformation capture (3C) technique. We use this approach to study architecture at high spatial temporal resolution through in vivo mouse erythroid differentiation. Integrated...
Eukaryotic genomes are organized by loop extrusion and sister chromatid cohesion, both mediated the multimeric cohesin protein complex. Understanding how holds DNAs together, loss of cohesion causes age-related infertility in females, requires knowledge as to cohesin's stoichiometry vivo. Using quantitative super-resolution imaging, we identified two discrete populations chromatin-bound postreplicative human cells. Whereas most complexes appear dimeric, that localized sites associated with...
Transmissible chromosomal instability, characterized by non-clonal cytogenetic aberrations with a high frequency of chromatid-type together lower chromosome-type aberrations, has been demonstrated in the clonal descendants human haemopoietic stem cells after alpha- but not X-irradiation. Comparable abnormalities have also cultures alpha-irradiated primary bone marrow, different pattern delayed mainly chromosome-type, was found X-irradiation cultures. In analyses, apoptotic cell death evident...
We have isolated several cDNA clones from a lambda gt11 expression library by screening with antibodies prepared against the microsomal enzyme steroid sulfatase, which is deficient in classical X-chromosome-linked ichthyosis patients. One of these (p422) has been assigned mapping somatic cell hybrid panel and situ hybridization to Xp22.3. Clone p422 therefore coincident localization previously identified locus for sulfatase region X chromosome escaping inactivation. Twelve...