A5076210301- Kruppel-like factors research
- Adipose Tissue and Metabolism
- Hippo pathway signaling and YAP/TAZ
- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Alzheimer's disease research and treatments
- Vascular Malformations Diagnosis and Treatment
- Marine Sponges and Natural Products
- Genomics and Chromatin Dynamics
- Nerve injury and regeneration
- Erythrocyte Function and Pathophysiology
- Vascular Malformations and Hemangiomas
- Protein Tyrosine Phosphatases
- FOXO transcription factor regulation
- GDF15 and Related Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- Wnt/β-catenin signaling in development and cancer
- Anesthesia and Neurotoxicity Research
- Moyamoya disease diagnosis and treatment
- Amino Acid Enzymes and Metabolism
- Cytokine Signaling Pathways and Interactions
- RNA regulation and disease
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2022-2024
Max Delbrück Center
2022-2024
Max Planck Institute for Heart and Lung Research
2020-2022
Uppsala University
2015-2019
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2013-2016
Universitat Autònoma de Barcelona
2013
Universidad de Málaga
2004
Summary Aims Glial cell‐derived neurotrophic factor (GDNF) is emerging as a potent with therapeutic potential against range of neurodegenerative conditions including Alzheimer's disease (AD). We assayed the effects GDNF treatment in AD experimental models through gene‐therapy procedures. Methods Recombinant lentiviral vectors were used to overexpress gene hippocampal astrocytes 3xTg‐AD mice vivo , and also MC65 human neuroblastoma that conditionally overexpresses 99‐residue carboxyl‐terminal...
Endothelial cells (ECs) adapt their metabolism to enable the growth of new blood vessels, but little is known how ECs regulate adopt a quiescent state. Here, we show that metabolite S-2-hydroxyglutarate (S-2HG) plays crucial role in regulation endothelial quiescence. We find S-2HG produced after activation transcription factor forkhead box O1 (FOXO1), where it limits cell cycle progression, metabolic activity and vascular expansion. FOXO1 stimulates production by inhibiting mitochondrial...
Abstract Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to tissue’s metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient resources support growth proliferation. How nutrient acquisition usage are regulated unknown. Here we show that these processes instructed Yes-associated protein 1 (YAP)/WW domain-containing transcription regulator (WWTR1/TAZ)-transcriptional enhanced...
Formation and homeostasis of the vascular system requires several coordinated cellular functions, but their precise interplay during development relative importance for pathologies remain poorly understood. Here, we investigated endothelial functions regulated by Cdc42 in vivo relevance angiogenic sprouting morphogenesis postnatal mouse retina. We found that is required tip cell selection, directed migration filopodia formation, dispensable proliferation or apoptosis. Although loss seems...
Aberrant formation of blood vessels precedes a broad spectrum vascular complications; however, the cellular and molecular events governing malformations are not yet fully understood.Here, we investigated role CDC42 (cell division cycle 42) during morphogenesis its relative importance for development cerebrovascular malformations.To avoid secondary systemic effects often associated with embryonic gene deletion, generated an endothelial-specific inducible knockout approach to study postnatal...
Abstract Methods for modifying gene function at high spatiotemporal resolution in mice have revolutionized biomedical research, with Cre-loxP being the most widely used technology. However, technology has several drawbacks, including weak activity, leakiness, toxicity, and low reliability of existing Cre-reporters. This is mainly because different genes flanked by loxP sites (floxed) vary their sensitivity to Cre-mediated recombination. Here, we report generation, validation, utility...
The senescence-accelerated SAMP8 mouse is considered a useful non-transgenic model for studying aspects of progressive cognitive decline and Alzheimer's disease (AD). Using SAMR1 mice as controls, here we explored the effects 6 months voluntary wheel running in 10-month-old female mice. Exercise improved phenotypic features associated with premature aging (i.e., skin color body tremor) enhanced vascularization BDNF gene expression hippocampus compared controls. With aim identifying genes...
Despite its known expression in both the vascular endothelium and lung epithelium, until recently physiological role of adhesion receptor Gpr116/ADGRF5 has remained elusive. We generated a new mouse model constitutive Gpr116 inactivation, with large genetic deletion encompassing exon 4 to 21 gene. This allowed us confirm recent results defining as necessary regulator surfactant homeostasis. The loss provokes an early accumulation lungs, followed by massive infiltration macrophages,...
Abstract Puupehenone, a sesquiterpene produced by certain sponges, was selected in the course of blind screening for new potential inhibitors angiogenesis. In our study, we compare anti‐angiogenic activities puupehenone and another 11 related compounds that were either natural products from marine origin or their synthetic derivatives. The effects these determined with cell growth differentiation assays on bovine aorta endothelial cells. Our results show are weak to not selective However,...
Interleukin (IL)-6 is crucial for the induction of many murine models autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model multiple sclerosis. While IL-6-deficient mice (IL-6 KO) are resistant to EAE, we showed previously that in transgenic with astrocyte-targeted production IL-6-restricted cerebellum (GFAP-IL6), EAE induced MOG(35-55) was redirected away from spinal cord cerebellum. To further establish importance IL-6 produced central nervous system, have...
Aging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD). However, little knowledge currently available on molecular processes leading chronic neuroinflammation. In this context, recent studies have described role chromatin regulators in and longevity including REST corepressor (Rcor)-2 factor, which seems be involved an inflammatory suppressive program. To assess impact Rcor2 age-related...
Abstract Normal placental development and angiogenesis are crucial for fetal growth maternal health during pregnancy. However, molecular regulation of has been difficult to study due a lack specific genetic tools that isolate the placenta from embryo yolk sac. To address this gap in knowledge we recently developed Hoxa13 Cre mice which is expressed allantois-derived cells, including endothelial stromal cells. Mice lacking transcriptional regulators Yes-associated protein (YAP) PDZ-binding...