A5078697246- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- Health Systems, Economic Evaluations, Quality of Life
- Pharmaceutical Economics and Policy
- Cytokine Signaling Pathways and Interactions
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Neonatal Respiratory Health Research
- Biosimilars and Bioanalytical Methods
- Eosinophilic Disorders and Syndromes
- Aldose Reductase and Taurine
- Receptor Mechanisms and Signaling
- Alcohol Consumption and Health Effects
- Cardiac electrophysiology and arrhythmias
- Healthcare Policy and Management
- Cancer-related gene regulation
- Glaucoma and retinal disorders
- Cardiomyopathy and Myosin Studies
- Statistical Methods in Clinical Trials
- Healthcare innovation and challenges
- Galectins and Cancer Biology
- High Altitude and Hypoxia
- Adenosine and Purinergic Signaling
Medical University of Vienna
2008-2025
Ludwig Boltzmann Institute for Cancer Research
2016
University of Veterinary Medicine Vienna
2011-2016
Institute of Pharmacology
2012-2013
University of Vienna
2013
The transcription factor STAT1 is important in natural killer (NK) cells, which provide immediate defense against tumor and virally infected cells. We show that mutation of a single phosphorylation site (Stat1-S727A) enhances NK cell cytotoxicity range accompanied by increased expression perforin granzyme B. Stat1-S727A mice display significantly delayed disease onset cell-surveilled models including melanoma, leukemia, metastasizing breast cancer. Constitutive S727 depends on...
Mice with an impaired Type I interferon (IFN) signaling (IFNAR1- and IFNβ-deficient mice) display increased susceptibility toward v-ABL-induced B-cell leukemia/lymphoma. The enhanced leukemogenesis in the absence of intact IFN is caused by alterations within tumor environment. Deletion Ifnar1 cells (as obtained Ifnar1f/f CD19-Cre failed to impact on disease latency or type. In line this observation, initial transformation proliferative capacity were unaltered irrespective whether expressed...
Abstract Hematopoietic stem cells (HSCs) are characterized by the ability to self-renew and replenish hematopoietic system. The cell-cycle kinase cyclin-dependent 6 (CDK6) regulates transcription, whereby it has both kinase-dependent kinase-independent functions. Herein, we describe complex role of CDK6, balancing quiescence, proliferation, self-renewal, differentiation in activated HSCs. Mouse HSCs expressing kinase-inactivated CDK6 show enhanced long-term repopulation homing, whereas...
The expanding field of hematopoietic cell transplantation (HCT) for non-malignant diseases, including those amenable to gene therapy or editing, faces challenges due limited donor availability and the toxicity associated with collection methods. Umbilical cord blood (CB) represents a readily accessible source stem progenitor cells (HSPCs); however, dose obtainable from single unit is frequently insufficient. This limitation can be addressed by enhancing potency HSPCs, specifically their...
Background PI3Kδ is a lipid kinase of the phosphoinositide 3-kinase class 1A family and involved in early signaling events leukocytes regulating proliferation, differentiation survival. Currently, several inhibitors are under investigation for treatment hematopoietic malignancies. In contrast to beneficial effect inhibiting tumor cells, studies reported requirement function immune such as natural killer T helper cells. Cytotoxic lymphocytes (CTLs) essential surveillance. The scope this study...
Abstract Genetic deletion of the tyrosine kinase JAK2 or downstream transcription factor STAT5 in liver impairs growth hormone (GH) signalling and thereby promotes fatty disease. Hepatic deficiency accelerates tumourigenesis presence high GH levels. To determine whether upstream exerts similar functions, we crossed mice harbouring a hepatocyte-specific (JAK2 Δhep ) to transgenic (GH tg compared them mice. Similar mice, resulted severe steatosis background. However, contrast deficiency, loss...
STAT1 is an important regulator of NK cell maturation and cytotoxicity. Although the consequences Stat1-deficiency have been described in detail underlying molecular functions cells are only partially understood. Here, we describe a novel non-canonical role that was unmasked expressing Stat1-Y701F mutant. This mutation prevents JAK-dependent phosphorylation, subsequent nuclear translocation cytokine-induced transcriptional activity as verified by RNA-seq analysis. As expected mice displayed...
Malignant cells acquire physiological mechanisms of immunosuppression to escape immune surveillance. Strategies counteract this suppression could help improve adoptive immunotherapy regimen. The intracellular second messenger cyclic AMP (cAMP) acts as a potent immunosuppressive signaling molecule in T-cells and is up-regulated by multiple tumor-relevant suppressive factors including prostaglandin E2 (PGE2), adenosine the functions regulatory T-cells. Consequently, we aimed abrogate cAMP...
Activation of G<sub>s</sub>-coupled receptors enhances engraftment hematopoietic stem and progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a prostacyclin analog approved for treatment pulmonary hypertension, can be repurposed to improve cell transplantation. Murine human HSPCs were isolated from bone marrow umbilical cord blood, respectively. Prostanoid receptor agonists combination thereof with forskolin their capacity stimulate [<sup>3</sup>H]cAMP accumulation in...
Background Hematopoietic stem cell (HSC) transplantation is a standard procedure in the treatment of hematological disorders and also applicable to support aggressive chemotherapy cancer. In practice, clinical outcome often limited by inefficient bone marrow (BM) engraftment or low numbers available cells. It would therefore be desirable enhance pharmacological stimulation. HSC require several signals for successful migration into marrow. One these provided stimulation Gas[1]. Pretreatment...
Sinusoidal obstruction syndrome (SOS) is a major complication after hematopoietic stem cell transplantation and belongs to group of diseases increasingly identified as transplant-related systemic endothelial disease. Administration defibrotide affords some protection against SOS, but the effect modest. Hence, there unmet medical need justifying preclinical search for alternative approaches. Prostaglandins exert protective actions on cells various vascular beds. Here, we explored therapeutic...
The promise of personalized care has not always translated into improvements in patient care. There are concerns among payers that advice for certain genetic tests been revoked, diagnostic can be costly, and there is fragmentation funding including tests. In addition, pharmaceutical companies seeking high prices new targeted drugs through designating them as orphan drugs. Consequently, a need to integrate current knowledge about the value genetic, biomarkers, prognostic drug therapies from...
Abstract The cell dose in umbilical cord blood units is a major determinant for the outcome of hematopoietic transplantation. Prostaglandin analogs and dipeptidylpeptidase-4 (DPP4/CD26)-inhibitors enhance ability stem cells (HSCs) to reconstitute hematopoiesis. Here we explored synergism between treprostinil, stable prostaglandin agonist, DPP4/CD26-inhibitor vildagliptin. combination treprostinil forskolin caused modest but statistically significant increase surface levels DPP4/CD26 on...
The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade plays an important role in hematopoiesis. A constitutive activation this pathway is found a broad variety diverse human murine leukemias lymphomas. Whereas STAT3 STAT5 accelerate initiate tumor formation, STAT1 generally considered suppressor. As shown by Kovacic et al. [1], accelerates leukemia formation up-regulation MHC class I on leukemic cells allowing them to escape natural killer (NK)...
Objectives: Reimbursement decisions on new medicines require an assessment of their value. In Austria, when applying for reimbursement medicines, pharmaceutical companies are also obliged to submit forecasts future sales. We systematically examined the accuracy these sales and hence usefulness evaluations. Methods: retrospectively analyzed applications 102 drugs submitted between 2005 2014, which were accepted outside hospitals, actual reimbursed available at least 3 years. The main outcome...
We have recently uncovered the indispensable role of phosphoinositide-3-kinase δ (PI3Kδ) at different stages canonical killing pathway cytotoxic T lymphocytes (CTLs). The interception PI3Kδ−conveyed signals has been considered a valuable therapeutic strategy in oncology. However, our observations predict that benefits this approach may be limited by trade-off between direct anticancer effects and an impaired ability CTLs NK cells to attack tumor cells.