A5075057662- Signaling Pathways in Disease
- FOXO transcription factor regulation
- CRISPR and Genetic Engineering
- Cell death mechanisms and regulation
- Genetic Neurodegenerative Diseases
- Protein Kinase Regulation and GTPase Signaling
- Cytokine Signaling Pathways and Interactions
- Invertebrate Immune Response Mechanisms
- Cell Adhesion Molecules Research
- Heat shock proteins research
- Amyotrophic Lateral Sclerosis Research
- Dermatological and Skeletal Disorders
- Pluripotent Stem Cells Research
- Autoimmune Bullous Skin Diseases
- Cancer Mechanisms and Therapy
- RNA Research and Splicing
- Viral Infectious Diseases and Gene Expression in Insects
- Wnt/β-catenin signaling in development and cancer
- Amino Acid Enzymes and Metabolism
- Phagocytosis and Immune Regulation
- 3D Printing in Biomedical Research
- Eicosanoids and Hypertension Pharmacology
- PI3K/AKT/mTOR signaling in cancer
- Folate and B Vitamins Research
- Muscle metabolism and nutrition
Leiden University Medical Center
2024
Hubrecht Institute for Developmental Biology and Stem Cell Research
2022
University of Groningen
2015-2018
University Medical Center Groningen
2014-2015
University of California, San Francisco
2002-2009
University Medical Center Utrecht
2000-2006
Universidad Católica de Santa Fe
2006
Pulmonary Associates
2002
Heidelberg University
2000
University Hospital Heidelberg
2000
Interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor regulate the survival, proliferation, differentiation of hematopoietic lineages. Phosphatidylinositol 3-kinase (PI3K) has been implicated in regulation these processes. Here we investigate molecular mechanism by which PI3K regulates cytokine-mediated proliferation survival murine pre-B-cell line Ba/F3. IL-3 was found to repress expression cyclin-dependent kinase inhibitor p27KIP1 through activation PI3K, this...
Abstract The cytokine IL-2 plays a very important role in the proliferation and survival of activated T cells. These effects are dependent on signaling through phosphatidylinositol 3-kinase (PI3K) pathway. We others have shown that PI3K, activation protein kinase B/Akt, inhibits transcriptional by number forkhead transcription factors (FoxO1, FoxO3, FoxO4). In this study we investigated these IL-2-induced cell survival. show regulates phosphorylation FoxO3 PI3K-dependent fashion....
AFX-like Forkhead transcription factors, which are controlled by phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling, involved in regulating cell cycle progression and death. Both arrest induction of apoptosis mediated part transcriptional regulation p27kip1. Here we show that the Forkheads AFX (FOXO4) FKHR-L1 (FOXO3a) also directly control retinoblastoma-like p130 protein cause upregulation expression. Detailed analysis demonstrates following Forkhead-induced arrest, cells...
Survival signals elicited by cytokines include the activation of phosphatidylinositol 3-kinase (PI3K), which in turn promotes protein kinase B (PKB). Recently, PKB has been demonstrated to phosphorylate and inactivate forkhead transcription factor FKHR-L1, a potent inducer apoptosis. To explore mechanisms underlying induction apoptosis after cytokine withdrawal or FKHR-L1 activation, we used cell line activity could be specifically induced. Both induced apoptosis, was preceded an...
Background aimsFew human induced pluripotent stem cell (hiPSC) lines are Good Manufacturing Practice (GMP)-compliant, limiting the clinical use of hiPSC-derived products. Here, we addressed this by establishing and validating an in-house platform to produce GMP-compliant hiPSCs that would be appropriate for producing both allogeneic autologous products.MethodsOur standard research protocol production was adapted translated into a platform. In addition generation hiPSC, entails methodology...
Most neurodegenerative diseases associated with protein aggregation are hallmarked by activation of astrocytes. However, how astrocytes activated or which signaling pathways in contribute to pathogenesis is not clear. One long-standing question whether the responses due stress damage themselves, because astrocytic cellular neurons. Here, we examine induced expression disease-associated, aggregation-prone proteins other cells. We also consequences these a model for neurodegeneration. first...
The serine/threonine kinase protein B (PKB/c-Akt) acts downstream of the lipid phosphoinositide 3-kinase (PI3K) and functions as an essential mediator in many growth-factor-induced cellular responses such cell cycle regulation, survival transcriptional regulation. PI3K activation generates 3′-phosphorylated phosphatidylinositol lipids(PtdIns3P) PKB requires PtdIns3P-dependent membrane translocation phosphorylation by upstream kinases. However function is also regulated interaction with other...
Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine (polyQ) disorder caused by CAG repeat expansion in the ataxin-3 (ATXN3) gene resulting toxic protein aggregation. Inflammation and oxidative stress are considered secondary factors contributing to progression of this neurodegenerative disease. There no cure that halts or reverses progressive neurodegeneration SCA3. Here we show overexpression cystathionine γ-lyase, central enzyme cysteine metabolism, protective Drosophila model for SCA3...
Cytosolic phospholipase A(2) (cPLA(2)) plays a critical role in various neutrophil functions including the generation of leukotrienes and platelet-activating factor release. Enzyme activity is regulated both by translocation to membrane Ca(2+)-dependent manner serine phosphorylation members mitogen-activated protein kinase (MAPK) family. In this report, we have investigated granulocyte/macrophage colony-stimulating (GM-CSF)-mediated signalling pathways regulation cPLA(2). GM-CSF-induced...
Several neurodegenerative diseases like Huntington's, a polyglutamine (PolyQ) disease, are initiated by protein aggregation in neurons. Furthermore, these also associated with multitude of responses non-neuronal cells the brain, particular glial cells, astrocytes. These have repeatedly been suggested to play disease-modulating role, but how may be exploited delay progression neurodegeneration has remained unclear. Interestingly, one molecular changes that astrocytes undergo includes...
Abstract Interleukin (IL)-5 is a hematopoietic cytokine able to regulate differentiation, survival, and effector functions of eosinophils. It binds specifically its receptor, which composed cytokine-specific α-chain β-chain shared with the receptors for IL-3 granulocyte macrophage-colony stimulating factor. The molecular mechanisms by IL-5 modulates eosinophil survival remain unclear. In this study, we demonstrate that withdrawal induces apoptosis through mitochondria-dependent pathway,...
Befitting oxygen's key role in life's processes, hypoxia engages multiple signaling systems that evoke pervasive adaptations. Using surrogate genetics a powerful biological model, we dissect poorly understood hypoxia-sensing and signal transduction system. Hypoxia triggers NO-dependent accumulation of cyclic GMP translocation cytoplasmic GFP-Relish (an NFkappaB/Rel transcription factor) to the nucleus Drosophila S2 cells. An enzyme capable eliminating NO interrupted specifically when it was...
Abstract Because excessive or inadequate responses can be detrimental, immune to infection require appropriate regulation. Networks of signaling pathways establish versatility responses. Drosophila melanogaster is a powerful model organism for dissecting conserved innate infection. For example, the Toll pathway, which promotes activation NF-κB transcription factors Dorsal/Dorsal-related factor (Dif), was first identified in Drosophila. Together with IMD acting upstream Relish, these...
Genome-wide screens that have viability as a readout been instrumental to identify essential genes. The development of gene knockout with the use CRISPR-Cas has provided more sensitive method these Here, we performed an exhaustive genome-wide CRISPR/Cas9 phenotypic rescue screen modulators cytotoxicity induced by pioneer transcription factor, DUX4. Misexpression DUX4 due failure in epigenetic repressive mechanisms underlies facioscapulohumeral muscular dystrophy (FHSD), complex muscle...