A5037478722- Ion channel regulation and function
- Botulinum Toxin and Related Neurological Disorders
- Cellular transport and secretion
- Wnt/β-catenin signaling in development and cancer
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Autophagy in Disease and Therapy
- Neurological disorders and treatments
- Nerve injury and regeneration
- Biochemical and Structural Characterization
- Axon Guidance and Neuronal Signaling
- Neuroscience and Neural Engineering
- Lipid Membrane Structure and Behavior
- Cancer-related gene regulation
- Cardiac electrophysiology and arrhythmias
- Genetic Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Electrochemical Analysis and Applications
- Cancer-related Molecular Pathways
- PARP inhibition in cancer therapy
- 3D Printing in Biomedical Research
- Trace Elements in Health
- Ion Channels and Receptors
- RNA Research and Splicing
- Hereditary Neurological Disorders
Biomedical Research Institute of Lleida
2014-2024
Universitat de Lleida
2014-2024
Hospital Universitari Arnau de Vilanova
2008-2010
University College London
2006
Imperial College London
2002
The Honourable Society of Lincoln's Inn
1999-2001
Institute of Neurobiology and Molecular Medicine
1999-2001
Universitat de Barcelona
1995-1997
Bellvitge University Hospital
1995
Columbia University Irving Medical Center
1994
Proper dialogue between presynaptic neurons and their targets is essential for correct synaptic assembly function. At central synapses, Wnt proteins function as retrograde signals to regulate axon remodeling the accumulation of proteins. Loss Wnt7a leads defects in localization markers morphology axons. We show that loss Dishevelled-1 (Dvl1) mimics enhances phenotype cerebellum. Although active zones appear normal, electrophysiological recordings cerebellar slices from Wnt7a/Dvl1 double...
Glioblastoma multiforme is resistant to conventional anti-tumoral treatments due its infiltrative nature and capability of relapse; therefore, research efforts focus on characterizing gliomagenesis identifying molecular targets useful therapy. New therapeutic strategies are being tested in patients, such as Histone deacetylase inhibitors (HDACi) either alone or combination with other therapies. Here two HDACi included clinical trials have been tested, suberanilohydroxamic acid (SAHA)...
Tetanus (TeNT) is a zinc protease that blocks neurotransmission by cleaving the synaptic protein vesicle-associated membrane protein/synaptobrevin. Although its intracellular catalytic activity well established, mechanism which this neurotoxin interacts with neuronal surface not known. In study, we characterize p15s, first plasma TeNT binding proteins and show they are glycosylphosphatidylinositol-anchored glycoproteins in nerve growth factor (NGF)-differentiated PC12 cells, spinal cord...
ABSTRACT Tetanus and botulinum neurotoxins constitute a family of bacterial protein toxins responsible for two deadly syndromes in humans (tetanus botulism, respectively). They bind with high affinity to neurons wherein they cause complete inhibition evoked neurotransmitter release. Here we report on the cloning, expression use recombinant fragments heavy chains tetanus neurotoxin serotypes A, B E as tools study neurospecific binding holotoxins. We found that 50 kDa carboxy-terminal domains...
Glioblastoma multiforme (GBM) is a commonly occurring brain tumor with poor prognosis. GBM can develop both "de novo" or evolve from previous astrocytoma and characterized by high proliferation infiltration into the surrounding tissue. Following treatment (surgery, radiotherapy, chemotherapy), tumors often reappear. Glioma-initiating cells (GICs) have been identified in are thought to be responsible for initiation, their continued growth, recurrence. β-catenin, component of cell-cell...
WNT-CTNN1B signaling promotes cancer cell proliferation and stemness. Furthermore, recent evidence indicates that macroautophagy/autophagy regulates WNT signaling. Here we investigated the impact of inhibiting on autophagy in glioblastoma (GBM), a devastating brain tumor. Inhibiting TCF, or silencing TCF4 CTNNB1/β-catenin upregulated SQSTM1/p62 GBM at transcriptional protein levels and, turn, autophagy. DKK1/Dickkopf1, canonical receptor antagonist, also induced autophagic flux. Importantly,...
We have recently reported that human melanoma cells express a variety of voltage-gated calcium (Ca(2+) ) channel types, including low-voltage-activated T-type channels play significant role in cell cycle progression. Here, we challenged metastatic with blockers clinical use and found dual effect on viability: (i) reduction the proliferation rate, through halt progression to G1 -S phase; (ii) promotion death was partially dependent activation caspases. An in-depth analysis process showed...
Synaptotagmins constitute a large family of membrane proteins characterized by their distinct distributions and different biochemical features. Genetic evidence suggests that members this protein are likely to function as calcium sensors in calcium-regulated events neurons, although the precise molecular mechanism remains ill defined. Here we demonstrate synaptotagmin isoforms (Syt I, II, IV) present same synaptic vesicle population from rat brain cortex. In addition, Syt I II co-localize on...
Abstract: Tetanus neurotoxin is one of the most powerful protein toxins known, acting in vivo at femtomolar doses. Two main factors determine its high potency: a protease activity restricted to single intracellular substrate and absolute neurospecificity. Whereas enzymatic properties tetanus toxin have been thoroughly defined, nature neuronal receptor(s) their involvement trafficking are poorly understood. Using binding crosslinking experiments, we report here on characterisation an N...
Abstract Wnt factors regulate neural stem cell development and neuronal connectivity. Here we investigated whether Wnt‐3a Wnt‐3 , expressed in the developing spinal cord, proliferation differentiation of cord precursors (SCNP). promoted a sustained increase SCNP decreased expression cyclin‐dependent kinase inhibitors. In contrast, transiently enhanced increased neurogenesis through β‐catenin signaling. Furthermore, both stimulated neurite outgrowth SCNP‐derived neurons β‐catenin‐...
The expression of voltage-gated calcium channels (VGCCs) has not been reported previously in melanoma cells spite increasing evidence a role VGCCs tumorigenesis and tumour progression. To address this issue we have performed an extensive RT-PCR analysis VGCC human melanocytes range cell lines biopsies. In addition, tested the functional these using Ca(2+) imaging techniques examined their relevance for viability proliferation cells. Our results show that control express channel isoforms...
Abstract Glioblastoma (GBM) is a highly malignant brain tumour characterised by limited treatment options and poor prognosis. The microenvironment, particularly the central hypoxic region of tumour, known to play pivotal role in GBM progression. Cells within this adapt hypoxia stabilising transcription factor HIF1-α, which promotes cell proliferation, dedifferentiation chemoresistance. In study we sought examine effects NNC-55-0396, tetralol compound overactivates unfolded protein response...
Tetanus neurotoxin (TeNT) is a powerful bacterial protein toxin that cleaves VAMP/synaptobrevin, an essential of the synaptic vesicle fusion machinery, and consequently blocks neurotransmission. The extreme neurospecificity TeNT determined by binding its C-terminal domain (fragment C or H(C)) to neuronal receptors. Whereas polysialogangliosides are known acceptors for toxin, existence additional receptors has also been suggested. We have reported previously on 15 kDa cell-surface...
Tyrosine phosphorylation of beta-catenin, a component adhesion complexes and the Wnt pathway, affects cell adhesion, migration gene transcription. By reducing beta-catenin availability using shRNA-mediated silencing or expression intracellular N-cadherin, we show that is required for axon growth downstream brain-derived neurotrophic factor (BDNF) signalling hepatocyte (HGF) signalling. We demonstrate receptor tyrosine kinases (RTKs) Trk Met interact with phosphorylate beta-catenin....
Tetanus neurotoxin (TeNT) is a powerful bacterial protein toxin that cleaves VAMP/synaptobrevin, an essential of the synaptic vesicle fusion machinery, and consequently blocks neurotransmission. The extreme neurospecificity TeNT determined by binding its C-terminal domain (fragment C or HC) to neuronal receptors. Whereas polysialogangliosides are known acceptors for toxin, existence additional receptors has also been suggested. We have reported previously on 15 kDa cell-surface glycoprotein...
Cutaneous malignant melanoma arises from transformed melanocytes de novo or congenital acquired melanocytic naevi. We have recently reported that T-type Ca2+ channels (TT-Cs) are upregulated in human and play an important role cell proliferation.To describe for the first time formalin-fixed paraffin-embedded tissue immunoexpression of TT-Cs biopsies normal skin, naevi melanoma, order to evaluate their melanomagenesis and/or tumour progression, utility as prognostic markers possible use...
Abstract T-type Ca2+ channels (TTCC) have been identified as key regulators of cancer cell cycle and survival. In vivo studies in glioblastoma (GBM) murine xenografts shown that drugs able to block TTCC vitro (such tetralol derivatives mibefradil/NNC-55-096, or different 3,4-dihydroquinazolines) slow tumor progression. However, currently available pharmacologic blockers limited selectivity for are unable distinguish between isoforms. Here we analyzed the expression transcripts human GBM...
Focal adhesion kinase (FAK) is a central component of focal adhesions that regulate cancer cell proliferation and migration. Here, we studied the effects FAK inhibition in glioblastoma (GBM), fast growing brain tumor has poor prognosis. Treating GBM cells with inhibitor PF-573228 induced proliferative arrest increased size. also reduced growth neurospheres. These were associated p27/CDKN1B levels β-galactosidase activity, compatible acquisition senescence. Interestingly, repressed expression...
Axon morphogenesis is a complex process regulated by variety of secreted molecules, including morphogens and growth factors, resulting in the establishment neuronal circuitry. Our previous work demonstrated that factors [Neurotrophins (NT) Hepatocyte Growth Factor (HGF)] signal through β-catenin during axon morphogenesis. HGF signaling promotes outgrowth branching inducing phosphorylation at Y142 transcriptional regulation T-Cell (TCF) target genes. Here, we asked which genes are An array...
Abstract Glioblastoma (GBM) is a highly invasive brain neoplasia with an elevated recurrence rate after surgical resection. The cyclin D1 (Ccnd1)/Cdk4–retinoblastoma 1 (RB1) axis frequently altered in GBM, leading to overproliferation by RB1 deletion or Ccnd1‐Cdk4 overactivation. High levels of also promote GBM cell invasion mechanisms that are not so well understood. purpose this work elucidate the vivo role cytoplasmic activity dissemination GBM. We show Ccnd1 activates primary human cells...
Summary Melanoma is a malignant tumor derived from melanocytes. Once disseminated, it usually highly resistant to chemotherapy and associated with poor prognosis. We have recently reported that T‐type calcium channels ( TTCC s) are overexpressed in melanoma cells play an important role progression. Importantly, pharmacological blockers reduce proliferation deregulate autophagy leading apoptosis. Here, we analyze the of during migration/invasion cells. Cav3.1 LC 3‐ II proteins expressed BRAFV...