A5083713000- Macrophage Migration Inhibitory Factor
- Nuclear Receptors and Signaling
- Global Peace and Security Dynamics
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- Chronic Lymphocytic Leukemia Research
- African history and culture analysis
- Acute Lymphoblastic Leukemia research
- Radiopharmaceutical Chemistry and Applications
- Carbon dioxide utilization in catalysis
- Chronic Myeloid Leukemia Treatments
- African history and culture studies
- Cytokine Signaling Pathways and Interactions
- Immunodeficiency and Autoimmune Disorders
- Transplantation: Methods and Outcomes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Microbial metabolism and enzyme function
- Peptidase Inhibition and Analysis
- T-cell and Retrovirus Studies
- Lymphoma Diagnosis and Treatment
- Tendon Structure and Treatment
- Cardiac electrophysiology and arrhythmias
- Cardiac Imaging and Diagnostics
- Immune cells in cancer
- Radio Frequency Integrated Circuit Design
University of Veterinary Medicine Vienna
2015-2024
West Virginia University
2022
Institute of Pharmacology
2022
Ludwig Boltzmann Institute for Cancer Research
2015-2019
University of Veterinary Medicine
2018
Medical University of Vienna
2006-2018
RELX Group (United States)
2017
University Hospital of Bern
2011
Triemli Hospital
2004
Stanford University
2003
Abstract Immune cells need to sustain a state of constant alertness over lifetime. Yet, little is known about the regulatory processes that control fluent and fragile balance called homeostasis. Here we demonstrate JAK-STAT signaling, beyond its role in immune responses, major regulator cell We investigated JAK-STAT-mediated transcription chromatin accessibility across 12 mouse models, including knockouts all STAT factors TYK2 kinase. Baseline signaling was detected CD8 + T macrophages...
The transcription factor STAT5 is an essential downstream mediator of many tyrosine kinases (TKs), particularly in hematopoietic cancers. activated by FLT3-ITD, which a constitutively active TK driving the pathogenesis acute myeloid leukemia (AML). Since critical diverse malignant properties AML cells, direct targeting significant clinical value. Here, we describe development and preclinical evaluation novel, potent SH2 domain inhibitor, AC-4-130, can efficiently block pathological levels...
Abstract T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature malignancy. Here we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), nucleotide sequences 111 well-characterized patients. Besides prominent signatures activation prevalent clonal variants, also identify novel hot-spots for CN variability, fusion molecules, alternative transcripts, progression-associated dynamics. The overall lesional spectrum T-PLL mainly...
STAT5B is often mutated in hematopoietic malignancies. The most frequent mutation, Asp642His (N642H), has been found over 90 leukemia and lymphoma patients. Here, we used the Vav1 promoter to generate transgenic mouse models that expressed either human or STAT5BN642H compartment. While STAT5B-expressing mice lacked a phenotype, STAT5BN642H-expressing rapidly developed T cell neoplasms. Neoplasia manifested as transplantable CD8+ leukemia, indicating mutation drives cancer development....
Abstract The transcription factor STAT3 is frequently activated in human solid and hematological malignancies remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, interfere signaling. These monobodies are highly selective for bind nanomolar affinity the N-terminal coiled-coil domains. Interactome analysis detects significant binding other STATs or additional off-target proteins, confirming their exquisite...
Tissue-resident macrophages are of vital importance as they preserve tissue homeostasis in all mammalian organs. Nevertheless, appropriate cell culture models still limited. Here, we propose a novel model to study and expand murine primary alveolar (AMs), the tissue-resident lung, vitro over several months. By providing combination granulocyte-macrophage colony-stimulating factor, TGFβ, PPARγ activator rosiglitazone, maintain mouse ex vivo cultured AMs (mexAMs) MexAMs typical morphologic...
Abstract Patients with T- and natural killer (NK)-cell neoplasms frequently have somatic STAT5B gain-of-function mutations. The most frequent mutation is STAT5BN642H, which known to drive murine T-cell leukemia, although its role in NK-cell malignancies unclear. Introduction of the STAT5BN642H into human lines enhances their potential induce leukemia mice. We generated a mouse model that enables tissue-specific expression selectively expressed mutated hematopoietic cells (N642Hvav/+) or...
Deregulation of the Janus kinase/signal transducers and activators transcription (JAK/STAT) signaling pathway is found in cancer with STAT5A/B controlling leukemic cell survival disease progression. As mutations STAT5B, but not STAT5A, have been frequently described hematopoietic tumors, we used BCR/ABL as model systems to investigate contribution STAT5A or STAT5B for leukemogenesis. The absence decreased colony formation. Even more drastic effects were observed STAT5B. STAT5B-deficient...
Recurrent gain-of-function mutations in the transcription factors STAT5A and much more STAT5B were found hematopoietic malignancies with highest proportion mature T- natural killer-cell neoplasms (peripheral T-cell lymphoma, PTCL). No targeted therapy exists for these heterogeneous often aggressive diseases. Given shortage of models PTCL, we mimicked graded or activity by expressing hyperactive Stat5a variants at low high levels system transgenic mice. Only mice developed a lethal disease...
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature cancer. Mutations in IL7R have been analyzed genetically, but downstream effector functions such as STAT5A and STAT5B hyperactivation are poorly understood. Here, we studied the most frequent clinically challenging STAT5BN642H driver development cancer onset compared it with hyperactive variants transgenic mice. Enhanced STAT5 activity caused disrupted promoted early progenitor-ALL phenotype, upregulation of genes involved...
In 15 patients with acute myocardial infarction intravenous pentazocine in a dose of either 30 or 60 mg. was followed by significant increase mean pulmonary arterial pressure. the group receiving 60-mg. this change associated systemic pressure, total peripheral resistance, and left ventricular minute work. Because these circulatory effects would seem to be unsuitable for relief pain infarction.
Abstract High levels of macrophage migration inhibitory factor (MIF) in patients with cancer are associated poor prognosis. Its redox-dependent conformational isoform, termed oxidized MIF (oxMIF), is a promising tumor target due to its selective occurrence lesions and at inflammatory sites. A first-generation anti-oxMIF mAb, imalumab, was investigated clinical trials advanced solid tumors, where it well tolerated showed signs efficacy. However, imalumab has short half-life humans, increased...
IL-17-producing RORγt+ γδ T cells (γδT17 cells) are innate lymphocytes that participate in type 3 immune responses during infection and inflammation. Herein, we show γδT17 rapidly proliferate within neonatal lymph nodes gut, where, upon entry, they upregulate T-bet coexpress IL-17, IL-22, IFN-γ a STAT3- retinoic acid-dependent manner. Neonatal expansion was halted mice conditionally deficient STAT5, its loss resulted cell depletion from all adult organs. Hyperactive STAT5 mutant showed the...
Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are considered a breakthrough in cancer therapy. Currently approved for breast treatment, CDK4/6 extensively tested other subtypes. Frequently observed side effects include hematological abnormalities such as reduced numbers of neutrophils, erythroid cells platelets that associated with anemia, bleeding higher risk infections. In order to understand whether the adverse within hematopoietic system related CDK4 or CDK6 we generated...
Thoracostomy tube in an interlobar fissure: radiologic recognition of a potential problemMaurer, JR, PJ Friedman and VW WingAudio Available | Share