A5053420565- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Parkinson's Disease Mechanisms and Treatments
- Retinal Development and Disorders
- Olfactory and Sensory Function Studies
- Cellular transport and secretion
- Nuclear Receptors and Signaling
- Neurobiology and Insect Physiology Research
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Autophagy in Disease and Therapy
- Single-cell and spatial transcriptomics
- Nerve injury and regeneration
- Neuroscience and Neural Engineering
- Neurological disorders and treatments
- MicroRNA in disease regulation
- Adipose Tissue and Metabolism
- Advanced Memory and Neural Computing
- Mesenchymal stem cell research
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Genetic Neurodegenerative Diseases
- Pancreatic function and diabetes
- Neuroinflammation and Neurodegeneration Mechanisms
- Animal Genetics and Reproduction
KU Leuven
2023-2025
VIB-KU Leuven Center for Brain & Disease Research
2020-2025
Allen Institute for Brain Science
2023-2025
VIB-KU Leuven Center for Microbiology
2024
Universitat de Barcelona
2017-2023
Institut de Biomedicina de la Universitat de Barcelona
2019-2023
Center of Regenerative Medicine in Barcelona
2017-2023
Duran i Reynals Hospital
2019-2023
Bellvitge University Hospital
2018-2023
Institut d'Investigació Biomédica de Bellvitge
2018-2023
Parkinson's disease (PD) is associated with the degeneration of ventral midbrain dopaminergic neurons (vmDAns) and accumulation toxic α-synuclein. A non-cell-autonomous contribution, in particular astrocytes, during PD pathogenesis has been suggested by observational studies, but remains to be experimentally tested. Here, we generated induced pluripotent stem cell-derived astrocytes from familial mutant LRRK2 G2019S patients healthy individuals. Upon co-culture on top control vmDAns...
Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between makes it challenging to replicate key findings integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC deeply characterized their genetic properties using whole genome sequencing, genomic stability upon CRISPR-Cas9-based gene editing, including differentiation commonly used types. These studies...
Pathogenic α-synuclein and tau are critical drivers of neurodegeneration, their mutations cause neuronal loss in patients. Whether the underlying preferential vulnerability is a cell-type-intrinsic property or consequence increased expression levels remains elusive. Here, we explore cell-type-specific human brain datasets use deep phenotyping as well brain-wide single-cell RNA sequencing >200 live neuron types fruit flies to determine which cellular environments react most toxicity. We...
Neuronal activity causes use-dependent decline in protein function. However, it is unclear how this coupled to local quality control mechanisms. We show Drosophila that the endocytic Endophilin-A (EndoA) connects activity-induced calcium influx synaptic autophagy and neuronal survival a Parkinson disease-relevant fashion. Mutations disordered loop, including disease-risk mutation, render EndoA insensitive stimulation affect dynamics: when more flexible, its mobility membrane nanodomains...
Parkinson's disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to organization actin microtubule cytoskeletons, has been suggested participate pathogenesis. Nevertheless, its exact contribution remains obscure. To unveil participation family molecular pathogenesis disease, we first used C elegans demonstrate role small RAC1...
Obesity and its associated metabolic comorbidities are a rising global health social issue, with novel therapeutic approaches urgently needed. Adipose tissue plays key role in the regulation of energy balance adipose tissue-derived mesenchymal stem cells (AT-MSCs) have gained great interest cell therapy. Carnitine palmitoyltransferase 1A (CPT1A) is gatekeeper enzyme for mitochondrial fatty acid oxidation. Here, we aimed to generate adipocytes expressing constitutively active CPT1A form...
The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to emergence issues, patients frequently experience non-motor symptoms, such as sense smell (hyposmia). cellular molecular bases for these early defects remain enigmatic. To explore this, we developed new collection five fruit fly models familial conducted single-cell RNA sequencing young brains models....
Abstract Synaptic neurotransmission is a critical hallmark of brain activity and one the first processes to be affected in neural diseases. Monitoring this process, particular synaptic vesicle recycling, living cells has been instrumental unraveling mechanisms responsible for neurotransmitter release. However, currently available reporters suffer from major limitations such large probe size or lack suitability human neurons, hampering understanding pathophysiology. Here we describe NbLumSyt1...
The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to emergence issues, patients frequently experience non-motor symptoms, such as sense smell (hyposmia). cellular molecular bases for these early defects remain enigmatic. To explore this, we developed new collection five fruit fly models familial conducted single-cell RNA sequencing young brains models....
Abstract Patient-specific induced pluripotent stem cells (iPSCs) are a powerful tool to investigate the molecular mechanisms underlying Parkinson’s disease (PD), and might provide novel platforms for systematic drug screening. Several strategies have been developed generate iPSC-derived tyrosine hydroxylase (TH)-positive dopaminergic neurons (DAn), clinically relevant cell type in PD; however, they often result mixed neuronal cultures containing only small proportion of TH-positive DAn. To...
Abstract A deeper understanding of early disease mechanisms occurring in Parkinson’s (PD) is needed to reveal restorative targets. Here we report that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) obtained from healthy individuals or patients harboring LRRK2 PD-causing mutation can create highly complex networks with evident signs functional maturation over time. Compared control neuronal networks, PD patients’ displayed an elevated bursting behavior, the...
Abstract Tyrosine hydroxylase deficiency (THD) is a rare genetic disorder leading to dopaminergic depletion and early‐onset Parkinsonism. Affected children present with either severe form that does not respond L‐Dopa treatment (THD‐B) or milder responsive (THD‐A). We generated induced pluripotent stem cells (iPSCs) from THD patients were differentiated into neurons (DAn) compared control‐DAn healthy individuals gene‐corrected isogenic controls. Consistent patients, iPSC‐DAn displayed lower...
Abstract Somatic cells can be reprogrammed to induced pluripotent stem (iPS) by ectopic expression of the four factors Oct4, Klf4, Sox2, and Myc. Here, we investigated role Gata4 in reprogramming process present evidence for a negative this family transcription induction pluripotency. Coexpression with Sox2 or without Myc mouse embryonic fibroblasts greatly impaired endogenous Nanog expression. The lack upregulation was associated blockade transition from initiation phase full state...
Abstract The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to emergence issues, patients frequently experience non-motor symptoms, such as sense smell (hyposmia). cellular molecular bases for these early defects remain enigmatic. To explore this, we developed new collection five fruit fly models familial conducted single-cell RNA sequencing young brains models....
Presynaptic terminals can be located far from the neuronal cell body and are thought to independently regulate protein organelle turnover. In this work, we report a soma-centered mechanism that regulates autophagy-driven turnover at distant presynaptic in Drosophila. We show system is regulated by Rab39, whose human homolog mutated Parkinson's disease. Although Rab39 localized soma, its loss of function causes increased autophagy terminals, resulting faster synaptic neurodegeneration. Using...
Abstract Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between makes it challenging to replicate key findings integrate data across research groups. To address this issue, we sub-cloned candidate iPSC deeply characterised their genetic properties using whole genome sequencing, genomic stability upon CRISPR/Cas9-based gene editing, including differentiation commonly-used types. These studies...
The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to emergence issues, patients frequently experience non-motor symptoms, such as sense smell (hyposmia). cellular molecular bases for these early defects remain enigmatic. To explore this, we developed new collection five fruit fly models familial conducted single-cell RNA sequencing young brains models....
Abstract Neuronal activity and neurotransmitter release cause use-dependent decline in protein function. However, it is unclear how this coupled to local turnover quality control mechanisms. Here we show that the endocytic Endophilin-A (EndoA/ENDOA1) couples activity-induced calcium influx synaptic autophagy neuronal survival. We identify single mutations EndoA flexible region either increases diffusion promotes autophagosome formation absence of calcium, or immobilizes blocks autophagy,...
Abstract Tyrosine hydroxylase deficiency (THD) is a rare genetic disorder leading to dopaminergic depletion and early-onset parkinsonism. Affected children present with either severe form that does not respond L-Dopa treatment (THD-B), or milder responsive (THD-A). We generated induced pluripotent stem cells (iPSCs) from THD patients were differentiated into neurons (DAn) compared control-DAn healthy individuals gene-corrected isogenic controls. Consistent patients, iPSC-DAn displayed lower...