A5048453026- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Metabolism, Diabetes, and Cancer
- Cancer, Lipids, and Metabolism
- Melanoma and MAPK Pathways
- Selenium in Biological Systems
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Immunotherapy and Immune Responses
- Cutaneous Melanoma Detection and Management
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Bone Metabolism and Diseases
- T-cell and B-cell Immunology
- Diet and metabolism studies
- CAR-T cell therapy research
- Dermatology and Skin Diseases
- Mitochondrial Function and Pathology
- Redox biology and oxidative stress
- Immune Response and Inflammation
- Acute Lymphoblastic Leukemia research
- Cancer-related gene regulation
- Metabolomics and Mass Spectrometry Studies
The University of Texas Southwestern Medical Center
2017-2025
Essen University Hospital
2022-2025
Deutschen Konsortium für Translationale Krebsforschung
2022-2025
Children's Medical Center
2017-2025
University of Duisburg-Essen
2022-2024
German Cancer Research Center
2023-2024
National Center for Tumor Diseases
2023-2024
West German Heart and Vascular Center Essen
2024
Düsseldorf University Hospital
2024
Heinrich Heine University Düsseldorf
2024
Abstract Mammalian embryogenesis requires rapid growth and proper metabolic regulation 1 . Midgestation features increasing oxygen nutrient availability concomitant with fetal organ development 2,3 Understanding how metabolism supports approaches to observe directly in model organisms utero. Here we used isotope tracing metabolomics identify evolving programmes the placenta embryo during midgestation mice. These tissues differ metabolically throughout midgestation, but pinpointed gestational...
Abstract Epigenetic gene regulation and metabolism are highly intertwined, yet little is known about whether altered epigenetics influence cellular during cancer progression. Here, we show that EZH2 NRASG12D mutations cooperatively induce progression of myeloproliferative neoplasms to penetrant, transplantable, lethal myeloid leukemias in mice. EZH1, an homolog, indispensable for EZH2-deficient leukemia-initiating cells constitutes epigenetic vulnerability. BCAT1, which catalyzes the...
Abstract Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI currently being tested clinical trials. However, the benefits of this type regimen remain unclear. Here we identify mechanism glucocorticoid action that challenges long-standing dogma cytokine repression by receptor. Contrarily, synergistic gene induction sphingosine kinase 1 ( SphK1 ) and pro-inflammatory...
Article6 June 2018Open Access Source DataTransparent process NF-κB activation in astrocytes drives a stage-specific beneficial neuroimmunological response ALS Najwa Ouali Alami Department of Neurology, Ulm University, Ulm, Germany Search for more papers by this author Christine Schurr Institute Physiological Chemistry, Florian Olde Heuvel Linyun Tang Qian Li orcid.org/0000-0002-6621-2167 Alpaslan Tasdogan Immunology, Atsushi Kimbara Roche Pharma Research and Early Development, Innovation...
Abstract Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate structural basis autonomous activation CLL cells, showing that BcR immunoglobulins initiate intracellular through homotypic interactions between epitopes are specific for each subgroup patients with homogeneous clinicobiological profiles. The molecular details BcR–BcR apparently dictate clinical course disease,...
We previously discovered a new osteogenic growth factor that is required to maintain adult skeletal bone mass, Osteolectin/Clec11a. Osteolectin acts on Leptin Receptor+ (LepR+) stem cells and other progenitors in marrow promote their differentiation into osteoblasts. Here we identify receptor for Osteolectin, integrin α11, which expressed by LepR+ α11β1 binds with nanomolar affinity the response Osteolectin. Deletion of Itga11 (which encodes α11) from mouse human stromal impaired blocked...
Little is known about the metabolic regulation of rare cell populations because most metabolites are hard to detect in small numbers cells. We previously described a method for metabolomic profiling flow cytometrically isolated hematopoietic stem cells (HSCs) that detects 60 10,000 (Agathocleous et al., 2017). Here we describe new involving hydrophilic liquid interaction chromatography and high-sensitivity orbitrap mass spectrometry detected 160 HSCs, including many more glycolytic lipid...
Significance Melanoma metastasis is limited by oxidative stress. Cells that enter the blood experience high levels of reactive oxygen species and usually die ferroptosis. We found melanoma cells become more dependent upon pentose phosphate pathway to manage stress during metastasis. When function was impaired reduced glucose 6-phosphate dehydrogenase ( G6PD ) function, increased malic enzyme activity glutamine consumption. thus have redundant layered protection against
Abstract Purine nucleotides are necessary for various biological processes related to cell proliferation. Despite their importance in DNA and RNA synthesis, cellular signaling, energy-dependent reactions, the impact of changes purine levels on physiology remains poorly understood. Here, we find that depletion stimulates migration, despite effective reduction Blocking synthesis triggers a shunt glycolytic carbon into serine pathway, which is required induction migration upon depletion. The...
The bone marrow contains peripheral nerves that promote haematopoietic regeneration after irradiation or chemotherapy (myeloablation), but little is known about how this regulated. Here we found nerve growth factor (NGF) produced by leptin receptor-expressing (LepR+) stromal cells required to maintain fibres in adult marrow. In nerveless marrow, steady-state haematopoiesis was normal and vascular were impaired myeloablation. LepR+ cells, the adipocytes they gave rise to, increased NGF...
PD-1-based immune checkpoint inhibition (ICI) is the major backbone of current melanoma therapy. Tumor PD-L1 expression represents one few biomarkers predicting ICI therapy outcome. The objective present study was to systematically investigate whether type tumor tissue examined for has an impact on correlation with outcome.Pre-treatment collected within prospective DeCOG cohort ADOREG/TRIM (CA209-578; NCT05750511) between February 2014 and May 2020 from 448 consecutive patients who received...
The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition treatment-naive tumors, harbors active lymphoid populations at time initial diagnosis. Clinical anatomical imaging, single-cell molecular immune profiling quantification tumor reactivity...
Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional (3D) architecture of tissues and deciphering cellular spatial interactions under physiological pathological conditions. Deciphering interaction leptin receptor-expressing (LepR+) stromal cells other compartments in bone marrow crucial deeper understanding stem cell niche skeletal tissue. In this study, we introduce an optimized protocol 3D analysis tissues, enabling...
Abstract In patients with non–small cell lung cancer (NSCLC), the relationship between tumor metabolism and clinical outcomes is unknown. Here, 13C-labeled nutrients were intraoperatively infused into more than 90 surgically resectable pulmonary lesions, metabolic properties of resected tumors correlated survival. NSCLCs 13C-glucose, high 13C enrichment in tricarboxylic acid (TCA) cycle intermediates conferred a HR 3.8 for early death, typically metastasis. To test whether these features...