A5084325183- Chronic Myeloid Leukemia Treatments
- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- Angiogenesis and VEGF in Cancer
- Acute Lymphoblastic Leukemia research
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- HER2/EGFR in Cancer Research
- Lymphatic System and Diseases
- Phagocytosis and Immune Regulation
- Immune Response and Inflammation
- Kruppel-like factors research
- Cell Adhesion Molecules Research
- Virus-based gene therapy research
- Eosinophilic Disorders and Syndromes
- Advanced Breast Cancer Therapies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- T-cell and B-cell Immunology
- Protein Kinase Regulation and GTPase Signaling
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- PI3K/AKT/mTOR signaling in cancer
- Immunodeficiency and Autoimmune Disorders
Centre for Cancer Biology
2015-2025
University of South Australia
2015-2025
South Australia Pathology
2015-2025
Institute for Molecular Medicine Finland
2010-2023
Swedish Orphan Biovitrum (United States)
2023
University of Turku
2007-2020
University of Helsinki
2010-2015
Helsinki University Hospital
2010-2014
Hubrecht Institute for Developmental Biology and Stem Cell Research
2014
Wihuri Research Institute
2013-2014
Abstract Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease 1–7 , lupus-causing TLR7 gene variants is lacking. Here we describe lupus erythematosus caused by gain-of-function variant. sensor viral RNA 8 9 and binds to guanosine 10 – 12 . We identified de novo, previously undescribed missense Y264H variant in child with severe additional other patients lupus. The selectively increased sensing 2',3'-cGMP...
Hennekam lymphangiectasia-lymphedema syndrome (Online Mendelian Inheritance in Man 235510) is a rare autosomal recessive disease, which associated with mutations the CCBE1 gene. Because of striking phenotypic similarity embryos lacking either Ccbe1 gene or lymphangiogenic growth factor Vegfc gene, we searched for collagen- and calcium-binding epidermal domains 1 (CCBE1) interactions vascular endothelial factor-C (VEGF-C) signaling pathway, critical embryonic adult lymphangiogenesis.By...
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key drivers of blood lymph vessel formation in development, but also several pathological processes. VEGF-C signaling through VEGFR-3 promotes lymphangiogenesis, which is a clinically relevant target for treating lymphatic insufficiency blocking tumor angiogenesis metastasis. The extracellular domain VEGFRs consists seven Ig homology domains; domains 1-3 (D1-3) responsible ligand binding, the membrane-proximal 4-7...
Rationale: Lymphatic vessels in the respiratory tract normally mature into a functional network during neonatal period, but under some pathological conditions they can grow as enlarged, dilated sacs that result potentially lethal condition of pulmonary lymphangiectasia. Objective: We sought to determine whether overexpression lymphangiogenic growth factor (vascular endothelial factor-C [VEGF-C]) promote lymphatic and maturation tract. Unexpectedly, perinatal VEGF-C epithelium led resembling...
Pathological drug withdrawal syndrome is linked to accumulation of JAK2 phosphorylation in V617F myelofibrosis.
Cancer drugs targeting ErbB receptors, such as epidermal growth factor receptor and ErbB2, are currently in clinical use. However, the role of ErbB4 a potential cancer drug target has remained controversial. Recently, somatic mutations altering coding region were described patients with breast, gastric, colorectal, or non-small cell lung cancer, but functional significance these is unknown. Here we demonstrate that 2 10 cancer-associated lead to loss kinase activity due disruption...
The significance of ErbB4 in tumor biology is poorly understood. ERBB4 gene alternatively spliced producing juxtamembrane (JM-a and JM-b) cytoplasmic (CYT-1 CYT-2) isoforms. Here, signaling via the two alternative JM isoforms CYT-2 JM-b was compared. Fibroblasts expressing JM-a demonstrated enhanced autophosphorylation, growth, survival. In contrast, cells overexpressing underwent starvation-induced death. Both pro- antisurvival responses to were sensitive an ErbB kinase inhibitor....
Differences in how two ligands interact with VEGFR-1 explain why only one ligand is strongly angiogenic.
There is an unmet need for proangiogenic therapeutic molecules the treatment of tissue ischemia in cardiovascular diseases. However, major inducers angiogenesis such as vascular endothelial growth factor (VEGF/VEGF-A) have side effects that limit their utility vivo, especially at high concentrations. Angiopoietin-1 has been considered to be a blood vessel stabilization can inhibit intrinsic property VEGF promote leakiness. In this study, we designed and tested angiogenic properties chimeric...
Report14 February 2022Open Access Source DataTransparent process Targeting human CALR-mutated MPN progenitors with a neoepitope-directed monoclonal antibody Denis Tvorogov orcid.org/0000-0002-2009-1347 Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia Contribution: Conceptualization, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft, review & editing Search more...
Significance During the last decades, heart failure has developed into a major burden in western world, increasingly affecting millions. Cardiac hypertrophy is an adaptive response to myocardial infarction or increased blood pressure, and it often leads failure. Understanding underlying regulatory processes development of pathological needed for effective therapies. Our results show that kinase activity endothelial bone marrow chromosome X (Bmx) protein necessary cardiac hypertrophy. This...
Bmx, [corrected] also known as Etk, is a member of the Tec family nonreceptor tyrosine kinases. Bmx expressed mainly in arterial endothelia and myeloid hematopoietic cells. regulates ischemia-mediated arteriogenesis lymphangiogenesis, but its role tumor angiogenesis not known. In this study, we characterized function growth using both knockout transgenic mice. Isogenic colon, lung, melanoma xenotransplants showed reductions gene-deleted ((-/-)) mice, whereas developmental was affected....
Although integrin engagement initiates signaling events such as focal-adhesion kinase (FAK) and Src activation, the role of phosphoinositide turnover in cell adhesion is less clear. To assess PLC-gamma1 function this process, Plcg1(-/-) fibroblasts (Null) were compared with same which was re-expressed (Null+). Following plating on fibronectin, Null cells displayed a significantly impaired rate Null+ cells. This defect detected at low concentrations fibronectin; high fibronectin...
Leukemia stem cells (LSC) possess distinct self-renewal and arrested differentiation properties that are responsible for disease emergence, therapy failure, recurrence in acute myeloid leukemia (AML). Despite AML displaying extensive biological clinical heterogeneity, LSC with high interleukin-3 receptor (IL3R) levels a constant yet puzzling feature, as this lacks tyrosine kinase activity. Here, we show the heterodimeric IL3Rα/βc assembles into hexamers dodecamers through unique interface 3D...
Abstract Selective inhibitors of Janus kinase (JAK) 2 have been in demand since the discovery JAK2 V617F mutation present patients with myeloproliferative neoplasms (MPN); however, structural basis oncogenicity has only recently elucidated. New studies reveal a role for other domains, beyond domain, that contribute to pathogenic signaling. Here we evaluate structure-based approaches led recently-approved type I (fedratinib and pacritinib), as well II (BBT594 CHZ868) pseudokinase under...