A5091740410- Platelet Disorders and Treatments
- Blood groups and transfusion
- Cell death mechanisms and regulation
- Blood properties and coagulation
- Lipid metabolism and disorders
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Heparin-Induced Thrombocytopenia and Thrombosis
- Inflammatory Biomarkers in Disease Prognosis
- Phagocytosis and Immune Regulation
- Renal Diseases and Glomerulopathies
- Complement system in diseases
- Extracellular vesicles in disease
- Blood transfusion and management
- Erythrocyte Function and Pathophysiology
- Blood Coagulation and Thrombosis Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Glycosylation and Glycoproteins Research
- Multiple Myeloma Research and Treatments
- Social and Educational Sciences
- Antiplatelet Therapy and Cardiovascular Diseases
- T-cell and B-cell Immunology
- Venous Thromboembolism Diagnosis and Management
- Immune Response and Inflammation
- Chronic Myeloid Leukemia Treatments
Walter and Eliza Hall Institute of Medical Research
2015-2025
University of Gothenburg
2003-2025
Sahlgrenska University Hospital
2022-2025
The University of Melbourne
2015-2025
Region Västra Götaland
2024
Brigham and Women's Hospital
2003-2012
Harvard University
2003-2012
Institute of Molecular Medicine
2009
Indianapolis Zoo
2007
University of Copenhagen
2003
Cooling of blood platelets clusters the von Willebrand factor receptor complex. Macrophage alphaMbeta2 integrins bind to GPIbalpha subunit clustered complex, resulting in rapid clearance transfused, cooled platelets. This precludes refrigeration for transfusion, but current practice room temperature storage has major drawbacks. We document that is a lectin recognizes exposed beta-N-acetylglucosamine residues N-linked glycans on GPIbalpha. Enzymatic galactosylation chilled blocks recognition,...
It is believed that megakaryocytes undergo a specialized form of apoptosis to shed platelets. Conversely, range pathophysiological insults, including chemotherapy, are thought cause thrombocytopenia by inducing the apoptotic death and their progenitors. To resolve this paradox, we generated mice with hematopoietic- or megakaryocyte-specific deletions essential mediators apoptosis, Bak Bax. We found platelet production was unperturbed. In stark contrast, deletion prosurvival protein Bcl-x(L)...
Thrombopoietin (TPO) acting via its receptor, the cellular homologue of myeloproliferative leukemia virus oncogene (Mpl), is major cytokine regulator platelet number. To precisely define role specific hematopoietic cells in TPO-dependent hematopoiesis, we generated mice that express Mpl receptor normally on stem/progenitor but lack expression megakaryocytes and platelets (Mpl(PF4cre/PF4cre)). Mpl(PF4cre/PF4cre) displayed profound megakaryocytosis thrombocytosis with a remarkable expansion...
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...
Fli-1 and Erg are closely related members of the Ets family transcription factors. Both genes translocated in human cancers, including Ewing's sarcoma, leukemia, case Erg, more than half all prostate cancers. Although evidence from mice humans suggests that is required for megakaryopoiesis, normal adult hematopoietic stem cell (HSC) regulation, their precise physiological roles remain to be defined. To elucidate relationship between hematopoiesis, we conducted an analysis carrying mutations...
Abstract Navitoclax (ABT-263), an inhibitor of the pro-survival BCL-2 family proteins BCL-2, BCL-X L and BCL-W, has shown clinical efficacy in certain BCL-2-dependent haematological cancers, but causes dose-limiting thrombocytopaenia. The latter effect is caused by directly inducing apoptotic death platelets, which are dependent on for survival. Recently, ABT-199, a selective antagonist, was developed. It promising anti-leukaemia activity patients whilst sparing suggesting that megakaryocyte...
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...
alpha(M)beta(2) integrin receptors on myeloid cells mediate the adhesion or uptake of diverse ligands. Ligand binding occurs in alpha(M) chain, which is composed an I domain and a lectin domain. The binds iC3b, fibrinogen, intercellular molecule-1, other ligands mediates neutrophils to platelet glycoprotein Ibalpha (GPIbalpha). also recognizes beta-GlcNAc residues GPIbalpha that are clustered platelets after cooling. phagocytosis chilled could be reconstituted when Chinese hamster ovary were...
Gut ischemia is common in critically ill patients, promoting thrombosis and inflammation distant organs. The mechanisms linking hemodynamic changes the gut to remote organ remain ill-defined. We demonstrate that mouse induces a distinct pulmonary thrombotic disorder triggered by neutrophil macroaggregates. These aggregates lead widespread occlusion of arteries, veins, microvasculature. A similar neutrophil-rich response occurred humans with acute respiratory distress syndrome. Intravital...