A5010403946- Myeloproliferative Neoplasms: Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Cytokine Signaling Pathways and Interactions
- Platelet Disorders and Treatments
- Eosinophilic Disorders and Syndromes
- Lipid metabolism and disorders
- Chronic Myeloid Leukemia Treatments
- Kruppel-like factors research
- Renal and related cancers
- Mitochondrial Function and Pathology
- Chronic Lymphocytic Leukemia Research
- RNA regulation and disease
- Genetics, Aging, and Longevity in Model Organisms
- Tissue Engineering and Regenerative Medicine
- Biomedical Ethics and Regulation
- 3D Printing in Biomedical Research
- Epigenetics and DNA Methylation
- interferon and immune responses
- Microtubule and mitosis dynamics
- Osteoarthritis Treatment and Mechanisms
- Renal Diseases and Glomerulopathies
- Folate and B Vitamins Research
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
University of Oslo
2012-2023
Ludwig Cancer Research
2003-2023
de Duve Institute
2003-2023
UCLouvain
2005-2023
Walloon Excellence in Lifesciences and Biotechnology
2023
Oslo University Hospital
2012-2021
Whitehead Institute for Biomedical Research
2008-2011
Massachusetts Institute of Technology
2009-2011
Inserm
2005
Ectopic expression of defined transcription factors can reprogram somatic cells to induced pluripotent stem (iPS) cells, but the utility iPS is hampered by use viral delivery systems. Small molecules offer an alternative replace virally transduced with chemical signaling cues responsible for reprogramming. In this report we describe a small-molecule screening platform applied identify compounds that functionally reprogramming factor Klf4. A series scaffolds were identified activate Nanog in...
Endoplasmic reticulum (ER) stress is thought to activate autophagy via unfolded protein response (UPR)-mediated transcriptional up-regulation of machinery components and modulation microtubule-associated 1 light chain 3 (LC3). The upstream UPR constituents pancreatic EIF2-α kinase (PERK) inositol-requiring enzyme (IRE1) have been reported mediate these effects, suggesting that may stimulate PERK IRE1. However, how the its affect autophagic activity has not thoroughly examined. By analyzing...
The thrombopoietin receptor (TpoR) regulates hematopoietic stem cell renewal, megakaryocyte differentiation, and platelet formation. TpoR signals by activating Janus kinases JAK2 Tyk2. Here we show that, in addition to signaling downstream from the activated TpoR, Tyk2 strongly promote surface localization enhance total protein levels of TpoR. This effect is caused stabilization mature endoglycosidase H-resistant form receptor. Confocal microscopy indicates that colocalizes partially with...
The majority of polycythemia vera (PV) patients harbor a unique somatic mutation (V617F) in the pseudokinase domain JAK2, which leads to constitutive signaling. Here we show that homologous mutations JAK1 (V658F) and Tyk2 (V678F) lead activation these kinases. Their expression induces autonomous growth cytokine-dependent cells STAT5, STAT3, mitogen-activated protein kinase, Akt signaling Ba/F3 cells. mutant JAKs exhibit also when expressed fibrosarcoma deficient JAK proteins. Expression JAK2...
Activating mutations in JAK1 have been reported acute lymphoblastic leukemias, but little is known about the mechanisms involved their constitutive activation. Here, we studied ability of V658F and A634D to activate Janus kinase (JAK)/STAT pathway upon ectopic expression HEK293 cells alone or together with other components interleukin-9 receptor complex (IL-9Rα, γc, JAK3). Expression mutants failed trigger STAT activation, co-expression IL-9Rα chain promoted mutant phosphorylation Mutation...
Small molecules do the job: Somatic cells are reprogrammed into iPS upon ectopic expression of Oct4, Sox2, Klf4 and c-Myc. Application a cell-based, high-throughput chemical screen led to identification Src family kinase (SFK) inhibitors as replacements for retroviral Sox2 delivery. These compounds used study mechanisms underlying direct reprogramming may ultimately help bring cell technology one step closer clinical application.
The concentration of thiol and thioether metabolites in plasma has diagnostic value genetic diseases B-vitamin metabolism linked to methionine utilization. Among these, cysteine/cystine (Cys/CSSC) glutathione/oxidized glutathione (GSH/GSSG) act as cellular redox buffers. A new LC-MS/MS method was developed for the simultaneous detection cystathionine (Cysta), (Met), sulfoxide (MSO), creatinine reduced oxidized pairs homocysteine (Hcy/HSSH), cysteine (GSH/GSSG). one-step thiol-blocking...
Optic atrophy 1 (OPA1), a GTPase at the inner mitochondrial membrane involved in regulating fusion, stability, and energy output, is known to be crucial for neural development: Opa1 heterozygous mice show abnormal brain development, inactivating mutations OPA1 are linked human neurological disorders. Here, we used genetically modified embryonic patient-derived induced pluripotent stem cells reveal that haploinsufficiency leads aberrant nuclear DNA methylation significantly alters...
Hematopoietic stem cell renewal and differentiation are regulated through epigenetic processes. The conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5hmC) by ten-eleven-translocation enzymes provides new insights the regulation gene expression during development. Here, we studied potential regulatory role 5hmC human hematopoiesis. We used reduced representation profiling (RRHP) to characterize distribution in CD34+ cells, CD4+ T CD19+ B CD14+ monocytes granulocytes. In all...