A5065158992- Acute Myeloid Leukemia Research
- Protein Tyrosine Phosphatases
- Synthesis and biological activity
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- PI3K/AKT/mTOR signaling in cancer
- DNA and Nucleic Acid Chemistry
- Hematopoietic Stem Cell Transplantation
- Histone Deacetylase Inhibitors Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- Acute Lymphoblastic Leukemia research
- Microbial Natural Products and Biosynthesis
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune Response and Inflammation
- Retinoids in leukemia and cellular processes
- Single-cell and spatial transcriptomics
- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Antimicrobial Peptides and Activities
- DNA Repair Mechanisms
- Mesenchymal stem cell research
University of Copenhagen
2015-2024
Rigshospitalet
2014-2024
Copenhagen University Hospital
2003-2024
Novo Nordisk Foundation
2018-2023
National University Hospital
2023
National Cancer Centre Japan
2023
Foundation Center
2022
Skåne University Hospital
2011-2016
Business Innovation Centre
2013
Herlev Hospital
2004-2006
The p16INK4A and p14ARF proteins, encoded by the INK4A-ARF locus, are key regulators of cellular senescence, yet mechanisms triggering their up-regulation not well understood. Here, we show that ability oncogene BMI1 to repress locus requires its direct association is dependent on continued presence EZH2-containing Polycomb-Repressive Complex 2 (PRC2) complex. Significantly, EZH2 down-regulated in stressed senescing populations cells, coinciding with decreased levels associated H3K27me3,...
Abstract In addition to acting as a physical barrier against microorganisms, the skin produces antimicrobial peptides and proteins. After wounding, growth factors are produced stimulate regeneration of tissue. The factor response ceases after tissue, when protecting microbial infections is re-established. We found that important in wound healing, insulin-like I TGF-α, induce expression peptides/polypeptides human cationic protein hCAP-18/LL-37, β-defensin 3, neutrophil gelatinase-associated...
Nonsense-mediated mRNA decay (NMD) is a post-transcriptional surveillance process that eliminates mRNAs containing premature termination codons (PTCs). NMD has been hypothesized to impact on several aspects of cellular function; however, its importance in the context mammalian organism not addressed detail. Here we use mouse genetics demonstrate hematopoietic-specific deletion Upf2 , core factor, led rapid, complete, and lasting cell-autonomous extinction all hematopoietic stem progenitor...
Abstract To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model microarray technology define differentially expressed genes in PMNs from peripheral blood, that had transmigrated lesions. After migration lesions, demonstrated significant transcriptional response including several different functional categories. The up-regulation anti-apoptotic concomitant with down-regulation...
Distinct myeloid differentiation pathways give rise to either neutrophil/monocyte or basophil/mast cell/eosinophil lineages.
Myeloid neoplasms with erythroid or megakaryocytic differentiation include pure leukemia, myelodysplastic syndrome features, and acute megakaryoblastic leukemia (FAB M7) are characterized by poor prognosis limited treatment options. Here, we investigate the drug sensitivity landscape of these rare malignancies. We show that myeloid (AML) cells depend on antiapoptotic protein B-cell lymphoma (BCL)-XL, rather than BCL-2, using combined ex vivo testing, genetic perturbation, transcriptomic...
The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC or drive their differentiation, we relatively few insights into transcription that serve restrict differentiation. In present work, identify ETS (E-twenty-six)-related (ERG) as a critical factor protecting HSCs from Specifically, loss Erg accelerates by >20-fold, thus leading rapid depletion...
The HemaExplorer (http://servers.binf.ku.dk/hemaexplorer) is a curated database of processed mRNA Gene expression profiles (GEPs) that provides an easy display gene in haematopoietic cells. contains GEPs derived from mouse/human stem and progenitor cells as well more differentiated cell types. Moreover, data distinct subtypes human acute myeloid leukemia included the allowing researchers to directly compare leukemic with those their closest normal counterpart. Normalization batch correction...
Abstract Differentiation of multipotent stem cells into mature is fundamental for development and homeostasis mammalian tissues, requires the coordinated induction lineage-specific transcriptional programs cell cycle withdrawal. To understand underlying regulatory mechanisms this process, we investigated how tissue-specific transcription factors, CEBPA CEBPE, coordinate exit lineage-specification in vivo during granulocytic differentiation. We demonstrate that promotes by launching an...
CCAAT/enhancer binding protein (C/EBP)α is a myeloid-specific transcription factor that couples lineage commitment to terminal differentiation and cell cycle arrest, found mutated in 9% of patients who have acute myeloid leukemia (AML). We previously showed mutations which dissociate the ability C/EBPα block progression through E2F inhibition from its function as transcriptional activator impair vivo development neutrophil granulocyte adipose lineages. now show such increase capacity bone...
Multipotent self-renewing hematopoietic stem cells (HSCs) are responsible for reconstitution of all blood cell lineages. Whereas growth stimulatory cytokines have been demonstrated to promote HSC self-renewal, the potential role negative regulators remains elusive. Receptors tumor necrosis factor (TNF) and Fas ligand implicated as steady-state hematopoiesis, if overexpressed mediate bone marrow failure. However, it has proposed that progenitors rather than might be targeted by activation....
Differential gene expression in CD177+ and CD177- neutrophils was investigated, order to detect possible differences neutrophil function which could be related the pathogenesis of ANCA-associated Vasculitides (AAV).Neutrophils were isolated from healthy controls (HC) with high, negative or bimodal CD177 expression, sorted into subpopulations. Total RNA screened for 24,000 probes Illumina Ref-8 Beadchips. Genes showing differential between subsets microarray analysis re-assessed using...