A5047286815- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Lipoproteins and Cardiovascular Health
- Cancer, Lipids, and Metabolism
- interferon and immune responses
- Acute Lymphoblastic Leukemia research
- Immune Response and Inflammation
- Cancer, Stress, Anesthesia, and Immune Response
- Tryptophan and brain disorders
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Chemokine receptors and signaling
- DNA and Nucleic Acid Chemistry
- Ferroptosis and cancer prognosis
- Cell Adhesion Molecules Research
- Viral Infections and Outbreaks Research
- Liver Disease Diagnosis and Treatment
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- Childhood Cancer Survivors' Quality of Life
- Histone Deacetylase Inhibitors Research
- Peroxisome Proliferator-Activated Receptors
German Center for Infection Research
2023-2025
Heinrich Heine University Düsseldorf
2017-2025
University Hospital Bonn
2023-2025
Düsseldorf University Hospital
2023
Deutsche José Carreras Leukämie-Stiftung
2023
University of Duisburg-Essen
2013-2020
University of Toronto
2013-2020
Princess Margaret Cancer Centre
2010-2020
University Health Network
2009-2020
Ontario Institute for Cancer Research
2009-2013
Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver‐damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) mice leads to severe despite increased reticulocyte numbers. Bilirubin stimulated suicidal death human Mechanistically, bilirubin triggered rapid Ca 2+ influx,...
New therapies are urgently needed for hematologic malignancies, especially in patients with relapsed acute myelogenous leukemia (AML) and multiple myeloma. We others have previously shown that FDA-approved statins, which used to control hypercholesterolemia target the mevalonate pathway (MVA), can trigger tumor-selective apoptosis. Our goal was identify other drugs synergize statins further enhance anticancer activity of vivo. Using a screen composed FDA approved drugs, we identified...
CD8+ T-cell functions are critical for preventing chronic viral infections by eliminating infected cells. For healthy immune responses, beneficial destruction of cells must be balanced against immunopathology resulting from collateral damage to tissues. These processes regulated factors controlling function, which still incompletely understood. Here, we show that the interferon regulatory factor 4 (IRF4) and its cooperating binding partner B-cell-activating transcription (BATF) necessary...
Rapid activation of immune responses is necessary for antibacterial defense, but excessive can result in life-threatening septic shock. Understanding how these processes are balanced may provide novel therapeutic potential treating inflammatory disease. Fc receptors crucial innate activation. However, the role putative receptor IgM, known as Toso/Faim3, has to this point been unclear. In study, we generated Toso-deficient mice and used them uncover a critical regulatory function Toso...
Innate immune activation is essential to mount an effective antiviral response and prime adaptive immunity. Although a crucial role of CD169+ cells during vesicular stomatitis virus (VSV) infections increasingly recognized, factors regulating viral remain unclear. Here, we show that tumor necrosis factor produced by CD11b+ Ly6C+ Ly6G+ following infection with VSV. The absence TNF or receptor 1 (TNFR1) resulted in reduced numbers type I interferon (IFN-I) production VSV infection, severe...
// Aleksandra A. Pandyra 1, 2, 4 , Peter J. Mullen 1 Carolyn Goard 2 Elke Ericson 3, 5 Piyush Sharma Manpreet Kalkat Rosemary Yu Janice T. Pong Kevin R. Brown 3 Traver Hart Marinella Gebbia Karl S. Lang Guri Giaever 6 Corey Nislow Jason Moffat Linda Z. Penn Princess Margaret Cancer Centre, Toronto, ON, Canada Department of Medical Biophysics, University Donnelly Centre and Banting & Best Research, Institute Immunology, Faculty, Duisburg-Essen, Essen, Germany Now located at AstraZeneca...
Without the N terminus, iRhom proteins cannot properly limit ADAM17 activity, resulting in impaired cancer cell death.
Abstract B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is generating efficient B-cell responses. Although exerts limited influence on proliferation cells, expression induces survival proliferating via BTK/Syk/NF-κB-axis. The absence this cascade in naive Ceacam1 −/− mice limits cells. During systemic infection with cytopathic vesicular...
Cluster of differentiation (CD)8+ T cells are like a double edged sword during chronic viral infections because they not only promote virus elimination but also induce virus-mediated immunopathology. Elevated levels reactive oxygen species (ROS) have been reported infections. However, the role ROS in T-cell-mediated immunopathology remains unclear. Here we used murine lymphocytic choriomeningitis to explore processes and induction We found that infection led elevated producing granulocytes...
Abstract Background New therapies are urgently needed in melanoma particularly late-stage patients not responsive to immunotherapies and kinase inhibitors. Methods Drug screening, IC50 determinations as well synergy assays were detected by the MTT assay. Apoptosis using Annexin V 7AAD staining was assessed flow cytometry. TUNEL performed immunocytochemistry. Changes phosphorylation of key molecules PI3K/Akt/mTOR other relevant pathways western blot To assess vivo anti-tumor activity...
Elucidating key factors that regulate immune-mediated pathology in vivo is critical for developing improved strategies to treat autoimmune disease and cancer. NK cells can exhibit regulatory functions against CD8+ T following viral infection. Here we show while low doses of lymphocytic choriomeningitis virus (LCMV-WE) readily induce strong cell responses diabetes mice expressing the LCMV glycoprotein on -islet (RIP-GP mice), hyperglycemia does not occur after infection with higher LCMV....
Abstract HSP90 has emerged as an appealing anti-cancer target. However, inhibitors (HSP90i) are characterized by limited clinical utility, primarily due to the resistance acquisition via heat shock response (HSR) induction. Understanding roles of abundantly expressed cytosolic isoforms (α and β) in sustaining malignant cells’ growth mechanisms HSP90i is crucial for exploiting their potential. Utilizing multi-omics approaches, we identified that ablation HSP90β isoform induces overexpression...
Ferroptosis is a recently described type of regulated necrotic cell death whose induction has anti-cancer therapeutic potential, especially in hematological malignancies. However, efforts to uncover novel ferroptosis-inducing therapeutics have been largely unsuccessful. In the current investigation, we classified brightfield microscopy images tumor cells undergoing defined modes using deep transfer learning (DTL). The trained DTL network was subsequently combined with high-throughput...
Abstract PAX5 acts as a master regulator of B-cell proliferation and differentiation. Its germline somatic deregulation have both been implicated in the development precursor acute lymphoblastic leukemia (BCP-ALL). However, process how reduced transcriptional activity mediates progression to BCP-ALL, is still poorly understood. Here, we characterized longitudinal effects reduction on healthy, pre-leukemic BCP-ALL cells at single-cell level. Cell-surface marker analysis revealed...
NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV). However, regulating factors that maintain equilibrium between productive and are poorly understood. Here, we show a large load resulted in inhibition of activation, which correlated increased expression Qa-1b, ligand for inhibitory receptors. Qa-1b was predominantly upregulated on B following LCMV infection, this upregulation dependent type I...
Abstract Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged would represent major immunotherapeutic advance. Here we show arenaviruses lymphocytic choriomeningitis virus (LCMV) clinically used Junin vaccine (Candid#1) preferentially replicate cells variety murine human models. Viral replication leads to local activation,...
Immune activation within the tumor is one promising approach to induce immune-mediated regression. Certain viruses including oncolytic like herpes simplex virus (HSV) and non-oncolytic such as lymphocytic choriomeningitis (LCMV) are potent tools tumor-specific immune activation, however not all types respond viro- and/or immunotherapy mechanisms explaining differences remain be defined. We used non-cytopathic LCMV in different human melanoma models found that cell lines produced high levels...
Abstract Viral infections pose a significant global burden. Host susceptibility to pathogens is determined by many factors including genetic variation that can lead immunodeficient or dysregulated antiviral immune responses. Pax5 heterozygosity ( −/+ ), resulting in reduced PAX5 levels mice, mimics germline somatic dysregulation contributing diseases such as childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). In contrast the well-characterized roles of during early development,...