A5070514136- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Toxin Mechanisms and Immunotoxins
- Advanced Breast Cancer Therapies
- Monoclonal and Polyclonal Antibodies Research
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
- Galectins and Cancer Biology
- Cellular transport and secretion
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Single-cell and spatial transcriptomics
- Endoplasmic Reticulum Stress and Disease
- NF-κB Signaling Pathways
- PI3K/AKT/mTOR signaling in cancer
- Cell Image Analysis Techniques
- Acute Myeloid Leukemia Research
- Transgenic Plants and Applications
- Acute Lymphoblastic Leukemia research
- Lipid Membrane Structure and Behavior
- Liver Diseases and Immunity
Oslo University Hospital
2014-2025
University of Oslo
2014-2025
Memorial Sloan Kettering Cancer Center
2024
Nord University
2022
National Heart Lung and Blood Institute
2022
National Institutes of Health
2022
Council for Mental Health
2018
Medical University of Vienna
2012
Norwegian Institute of Public Health
2012
Norwegian Cancer Society
2006-2012
Increasing use of covalent and noncovalent inhibitors Bruton's tyrosine kinase (BTK) has elucidated a series acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance distinct enzymatic activities, including some that impair activity while imparting novel protein-protein interactions sustain receptor (BCR) signaling. Furthermore, describe clinical-stage IKZF1/3 degrader, NX-2127, can bind proteasomally degrade each mutant proteoform,...
Abstract Insight into the critical role of B-cell receptor signaling for pathogenesis chronic lymphocytic leukemia (CLL) led to development targeted therapies directed at key regulators cell survival. Agents targeting lymphoma-2 protein, Bruton’s tyrosine kinase (BTK), and phosphatidylinositol 3-kinase are approved treatment CLL, have significantly improved disease management. Nevertheless, acquired resistance is a challenge still be resolved. The mechanisms underlying becoming clearer,...
Interleukin (IL)-33 is a nuclear protein that released from stressed or damaged cells to act as an alarmin. We investigated the effects of IL-33 on endothelial cells, using prototype IL-1 family member, IL-1β, reference.Human umbilical vein were stimulated with showing highly similar phosphorylation signaling molecules, induction adhesion and transcription profiles. However, intradermally injected elicited significantly less proinflammatory activation when compared IL-1β led us observe...
The plant toxin ricin is transported from the plasma membrane via early endosomes and Golgi apparatus to endoplasmic reticulum. From this compartment, it enters cytosol inhibits protein synthesis. Lipid phosphorylation an important regulator of vesicular transport, in present study we have investigated role phosphatidylinositol (PI) 3‐kinase hVps34 retrograde transport ricin. Our data demonstrate that human embryonic kidney cells (HEK 293) dependent on PI(3)P. By using PI inhibitors, by...
Protein kinase C (PKC) isozymes regulate different vesicular trafficking steps in the recycling or degradative pathways. However, a possible role of these kinases retrograde pathway from endosomes to Golgi complex has previously not been investigated. We report here involvement specific PKC isozyme, PKCδ, intracellular transport glycolipid-binding Shiga toxin (Stx), which utilizes intoxicate cells. Upon binding cells, Stx was shown specifically activate PKCδ and PKCα. The PKCα then monitored...
Shiga toxin (Stx) binds to the cell, and it is transported via endosomes Golgi apparatus endoplasmic reticulum cytosol, where exerts its toxic effect. We have recently shown that Stx activates tyrosine kinase Syk, which in turn induces clathrin phosphorylation up-regulates uptake. Here, we show toxin-induced signaling can also regulate another step intracellular transport. demonstrate transport of dependent on mitogen-activated protein p38. Treatment cells with chemical inhibitors or small...
Full T-cell activation critically depends on the engagement of TCR (T-cell receptor) in conjunction with a second signal by co-stimulatory receptors that boost immune response. In present study we have compared signalling patterns induced two co-receptors CD2 and CD28 human peripheral blood T-cells. These were previously suggested to be redundant function. By combination multi-parameter phosphoflow cytometry, phosphokinase arrays Western blot analyses, demonstrate co-stimulation induces...
The microenvironment of chronic lymphocytic leukemia (CLL) cells in lymph nodes, spleen, and bone marrow provides survival, proliferation, drug resistance signals. Therapies need to be effective these compartments, pre-clinical models CLL that are used test sensitivity must mimic the tumor reflect clinical responses. Ex vivo have been developed capture individual or multiple aspects microenvironment, but they not necessarily compatible with high-throughput screens. Here, we report on a model...
Abstract Purpose: The management of chronic lymphocytic leukemia (CLL) has significantly improved with targeted therapies. However, many patients experience a suboptimal response. To optimally select the best therapy, predictive biomarkers are necessary. Here, we used PI3K inhibitor umbralisib as model to (i) understand how treatment affects cell signaling and immunophenotypes in responders non-responders; (ii) identify molecular features that predict individual responses; (iii) suggest...
<div>AbstractPurpose:<p>The management of chronic lymphocytic leukemia (CLL) has significantly improved with targeted therapies. However, many patients experience a suboptimal response. To optimally select the best therapy, predictive biomarkers are necessary. In this study, we used phosphoinositide 3-kinase (PI3K) inhibitor umbralisib as model to (i) understand impact treatment on cell signaling and immunophenotypes in responders nonresponders, (ii) identify molecular features...