A5008817816- Immune Cell Function and Interaction
- Platelet Disorders and Treatments
- RNA Research and Splicing
- Nuclear Structure and Function
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA Interference and Gene Delivery
- interferon and immune responses
- Cell death mechanisms and regulation
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- IL-33, ST2, and ILC Pathways
- Skin and Cellular Biology Research
- Kruppel-like factors research
- MicroRNA in disease regulation
- Cholesterol and Lipid Metabolism
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Malaria Research and Control
- Acute Lymphoblastic Leukemia research
- Zebrafish Biomedical Research Applications
- Asthma and respiratory diseases
- Immune cells in cancer
- Hematopoietic Stem Cell Transplantation
Walter and Eliza Hall Institute of Medical Research
2011-2024
The University of Melbourne
2009-2024
Oncode Institute
2012-2017
The Netherlands Cancer Institute
2012-2017
Institute of Molecular Medicine
2007
Platelets play a critical role in the pathogenesis of malarial infections by encouraging sequestration infected red blood cells within cerebral vasculature. But platelets also have well-established roles innate protection against microbial infections. We found that purified human killed Plasmodium falciparum parasites cultured cells. Inhibition platelet function aspirin and other inhibitors abrogated lethal effect exert on P. parasites. Likewise, platelet-deficient aspirin-treated mice were...
The LMO2 oncogene causes a subset of human T cell acute lymphoblastic leukemias (T-ALL), including four cases that arose as adverse events in gene therapy trials. To investigate the cellular origin LMO2-induced leukemia, we used fate mapping to study mice which Lmo2 was constitutively expressed thymus. induced self-renewal committed cells more than 8 months before development overt T-ALL. These self-renewing retained capacity for differentiation but several genes typical hematopoietic stem...
During haematopoiesis, haematopoietic stem cells differentiate into restricted potential progenitors before maturing the many lineages required for oxygen transport, wound healing and immune response. We have updated Haemopedia, a database of gene-expression profiles from broad spectrum cells, to include RNA-seq data both mice humans. The Haemopedia set covers wide range progenitors, with 57 mouse blood cell types (flow sorted populations healthy mice) 12 human types. This has been made...
Hematopoiesis is a multistage process involving the differentiation of stem and progenitor cells into distinct mature cell lineages. Here we present Haemopedia, an atlas murine gene-expression data containing 54 hematopoietic types, covering all lineages in hematopoiesis. We include rare populations such as eosinophils, mast cells, basophils, megakaryocytes, broad collection cells. show that lineage branching maturation during hematopoiesis can be reconstructed using expression patterns...
Abstract MLKL is the essential effector of necroptosis, a form programmed lytic cell death. We have isolated mouse strain with single missense mutation, Mlkl D139V , that alters two-helix ‘brace’ connects killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation salivary glands mediastinum. The normal embryonic development homozygotes until birth, absence...
Abstract During embryogenesis, haematopoietic and endothelial lineages emerge closely in time space. It is thought that the first blood endothelium derive from a common clonal ancestor, haemangioblast. However, investigation of candidate haemangioblasts vitro revealed capacity for mesenchymal differentiation, feature more compatible with an earlier mesodermal precursor. To date, no evidence vivo haemangioblast has been discovered. Using single cell RNA-Sequencing cellular barcoding, we have...
Polycomb group proteins are transcriptional repressors that play a central role in the establishment and maintenance of gene expression patterns during development. Using mice with an N-ethyl-N-nitrosourea (ENU)-induced mutation Suppressor Zeste 12 (Suz12), core component Repressive Complex 2 (PRC2), we show here loss Suz12 function enhances hematopoietic stem cell (HSC) activity. In addition to these effects on wild-type genetic background, mutations sufficient ameliorate defect...
Harlequin Ichthyosis (HI) is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, thought to regulate transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, nature scope this regulation remains unclear. As part an original recessive mouse ENU mutagenesis screen, we have identified characterised animal model HI showed that it displays many hallmarks including hyperkeratosis,...
Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes expression activated oncogenes, which causes Oncogene-Induced Senescence (OIS). A body evidence points involvement OIS chromatin reorganization, including formation senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) an important contributor genome organization and has been implicated cellular organismal...
How platelets are produced by megakaryocytes in vivo remains controversial despite more than a century of investigation. Megakaryocytes readily produce proplatelet structures vitro; however, visualization platelet release from proplatelets has remained elusive. We show that within the native prenatal and adult environments, frequency rate formation is incompatible with physiological demands replacement. resolve this inconsistency performing in-depth analysis plasma membrane budding, cellular...
Thrombopoietin (TPO), acting through its receptor Mpl, has two major physiological roles: ensuring production of sufficient platelets via stimulation megakaryocyte and maintaining hematopoietic stem cell (HSC) quiescence. Mpl also controls circulating TPO concentration receptor-mediated internalization degradation. Here, we demonstrate that the megakaryocytosis increased platelet mass in mice with mutations Myb or p300 genes causes reduced starvation stem-cell compartment, which is...
The transcription factor PU.1 is required for the development of mature myeloid and lymphoid cells. Due to this essential role importance in regulating several signature markers progenitors, its precise function early lymphopoiesis has been difficult define. Here, we demonstrate that was efficient generation lymphoid-primed multipotent progenitors (LMPPs) from hematopoietic stem cells subsequent formation common (CLPs). By contrast, further differentiation into B-cell lineage independent...
Carbohydrate modification of proteins includes N-linked and O-linked glycosylation, proteoglycan formation, glycosylphosphatidylinositol anchor synthesis, O-GlcNAc modification.Each these modifications requires the sugar nucleotide UDP-GlcNAc, which is produced via hexosamine biosynthesis pathway.A key step in this pathway interconversion GlcNAc-6-phosphate (GlcNAc-6-P) GlcNAc-1-P, catalyzed by phosphoglucomutase 3 (Pgm3).In paper, we describe two hypomorphic alleles mouse Pgm3 show there...
A fundamental question in microarray analysis is the estimation of number expressed probes different RNA samples. Negative control available latest platforms, such as Illumina whole genome expression BeadChips, provide a unique opportunity to estimate without setting threshold. novel algorithm was proposed this study an sample by utilizing these negative controls measure background noise. The performance demonstrated comparing generations set targeting well-characterized RefSeq NM...