A5024821428- PI3K/AKT/mTOR signaling in cancer
- Neurogenesis and neuroplasticity mechanisms
- Cancer Immunotherapy and Biomarkers
- Synthesis and Characterization of Heterocyclic Compounds
- Peptidase Inhibition and Analysis
- Galectins and Cancer Biology
- Cancer, Hypoxia, and Metabolism
- Pancreatic and Hepatic Oncology Research
- Synthesis and biological activity
- Nerve injury and regeneration
- Protein Kinase Regulation and GTPase Signaling
- Epigenetics and DNA Methylation
- Digital Imaging for Blood Diseases
- Cerebrospinal fluid and hydrocephalus
- AI in cancer detection
- Metabolism, Diabetes, and Cancer
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Mesenchymal stem cell research
- Fetal and Pediatric Neurological Disorders
- Anesthesia and Neurotoxicity Research
- Polyamine Metabolism and Applications
- Cell Image Analysis Techniques
- Developmental Biology and Gene Regulation
- Endoplasmic Reticulum Stress and Disease
Centro Andaluz de Biología Molecular y Medicina Regenerativa
2020-2025
Consejo Superior de Investigaciones Científicas
2020-2025
Universidad de Sevilla
2020-2025
Universidad Pablo de Olavide
2020-2025
Inserm
2018-2024
Université de Bordeaux
2018-2020
Angiogenesis and Cancer Microenvironment Laboratory
2020
University of Basel
2012-2019
University of Glasgow
2007-2014
Universidad de Málaga
2001-2007
Cancer cells metabolize glutamine mostly through glutaminolysis, a metabolic pathway that activates MTORC1. The AMPK-MTORC1 signaling axis is key regulator of cell growth and proliferation. Our recent investigation identified the connection between AMPK not restricted to glutaminolysis. Rather, we demonstrated crucial role ASNS (asparagine synthetase (glutamine-hydrolyzing)) GABA shunt for control during sufficiency. results elucidated network by which metabolism regulates...
Adult neurogenesis is tightly regulated through the interaction of neural stem/progenitor cells (NSCs) with their niche. Neurotransmitters, including GABA activation GABAA receptor ion channels, are important niche signals. We show that adult mouse hippocampal NSCs and progeny express metabotropic GABAB receptors. Pharmacological inhibition receptors stimulated NSC proliferation genetic deletion GABAB1 subunits increased differentiation neuroblasts in vivo. Cell-specific conditional supports...
Abstract Olfactory mucosal (OM) tissue, a potential source of stem cells, is currently being assessed in the clinic as candidate tissue for transplant-mediated repair spinal cord injury. We examined ability embryonic rat OM to generate cells using culture conditions known promote neural cell proliferation. Primary spheres formed that proliferated and exhibited two main morphologies: (a) CNS neurosphere-like (OM-I) (b) small, tight spheroid-like (OM-II). The OM-I expressed marker nestin but...
Abstract Glutamoptosis is the induction of apoptotic cell death as a consequence aberrant activation glutaminolysis and mTORC1 signaling during nutritional imbalance in proliferating cells. The role bioenergetic sensor AMPK glutamoptosis not defined yet. Here, we show that reactivation blocks both glutamine-dependent vitro vivo. We also glutamine used for asparagine synthesis GABA shunt to produce ATP inhibit AMPK, independently glutaminolysis. Overall, our results indicate metabolism...
Recurrent therapy resistance is a major limitation in clinical efficacy glioblastoma (GBM) patients, positioning GBM among the tumor types with poorest survival outcomes. In this work, we dissected mechanisms GBM, resulting identification of FGFR1 pathway as regulator signaling and metabolic rewiring associated temozolomide (TMZ) resistance. Hence, described mechanism that operates at two levels. First, p53-mediated regulation cell cycle arrest to allow DNA repair response TMZ. And second,...
Two phases may be recognized in the development of congenital hydrocephalus hyh mutant mouse. During embryonic life detachment ventral ependyma is followed by a moderate hydrocephalus. first postnatal week cerebral aqueduct becomes obliterated and severe develops. The aim present investigation was to elucidate cellular phenomena occurring at site obliteration probable participation subcommissural organ this process. Electron microscopy, immunocytochemistry, lectin histochemistry were used...
Hydrocephalic hyh mice are born with moderate hydrocephalus and a normal cerebral aqueduct. At about the fifth postnatal day aqueduct becomes obliterated severe develops. The aim of present investigation was to investigate mechanism this hydrocephalus, probably starting during fetal life when is still patent. By use immunocytochemistry scanning electron microscopy, mutant (n = 54) 61) mouse embryos were studied at various developmental stages trace earliest microscopic changes occurring in...
Proprotein convertases (PC) activate precursor proteins that play crucial roles in various cancers. In this study, we investigated whether PC enzyme activity is required for expression of the checkpoint protein programmed cell death 1 (PD-1) on cytotoxic T lymphocytes (CTL) colon cancer. Although altered secretory pathway was observed human cancers, only furin showed highly diffuse throughout tumors. Inhibition PCs cells using general protein-based inhibitor α1-PDX or pharmacologic...
The essential biometal manganese (Mn) serves as a cofactor for several enzymes that are crucial the prevention of human diseases. Whether intracellular Mn levels may be sensed and modulate signaling events has so far remained largely unexplored. highly conserved target rapamycin complex 1 (TORC1, mTORC1 in mammals) protein kinase requires divalent metal cofactors such magnesium (Mg2+) to phosphorylate effectors part homeostatic process coordinates cell growth metabolism with nutrient and/or...
Abstract Background Tumor resistance represents a major challenge in the current oncology landscape. Asparagine endopeptidase (AEP) overexpression correlates with worse prognosis and reduced overall survival most human solid tumors. However, underlying mechanisms of connection between AEP cancer patients remain unclear. Methods High-throughput proteomics, cellular molecular biology approaches clinical data from breast (BC) were used to identify novel, biologically relevant targets....
Abstract Background Tumor resistance represents a major challenge in the current oncology landscape. Asparagine endopeptidase (AEP) overexpression correlates with worse prognosis and reduced overall survival most human solid tumors. However, underlying mechanisms of connection between AEP cancer patients remain unclear. Methods High-throughput proteomics, cellular molecular biology approaches clinical data from breast (BC) were used to identify novel, biologically relevant targets....
Apelin is a well-established mediator of survival and mitogenic signaling through the apelin receptor (Aplnr) has been implicated in various cancers; however, little known regarding Elabela (ELA/APELA) signaling, also mediated by Aplnr, its role conversion precursor proELA into mature ELA cancer are unknown. Here, we identified function mTORC1 as an essential that repressed kidney tumor cell growth, migration, survival. Moreover, sunitinib showed synergistic effect repressing growth...
The cellular receptor Notch1 is a central regulator of T‐cell development, and as consequence, pathway appears upregulated in > 65% the cases acute lymphoblastic leukemia (T‐ALL). However, strategies targeting signaling render only modest results clinic due to treatment resistance severe side effects. While many investigations reported different aspects tumor cell growth progression controlled by Notch1, less known regarding modifications metabolism induced upregulation T‐ALL. Previously,...
Recent studies identified a highly tumorigenic subpopulation of glioma stem cells (GSCs) within malignant gliomas. GSCs are proposed to originate from transformed neural (NSCs). Several pathways active in NSCs, including the Notch pathway, were shown promote proliferation and tumorigenesis GSCs. Notch2 is expressed glioblastoma multiforme (GBM), astrocytoma. It therefore conceivable that increased signaling NSCs contributes formation GBM. Here, we demonstrate mice constitutively expressing...
Tumour progression and therapy tolerance are highly regulated complex processes largely dependent on the plasticity of cancer cells their capacity to respond stress. The higher highlights need for identifying targetable molecular pathways that challenge cell survival. Here, we show N7-guanosine methylation (m7G) tRNAs, mediated by METTL1, regulates survival stress conditions in cells. Mechanistically, find m7G tRNAs protects them from stress-induced cleavage processing into 5' tRNA...
Abstract Cell transplantation is one strategy for encouraging regeneration after spinal cord injury and a range of cell types have been investigated their repair potential. However, variations in study design complicate determination which cells are most effective. In this we carried out direct comparison the regenerative integrative properties several preparations following into lesioned rat cord. Transplants included: (i) purified olfactory ensheathing (OECs) (ii) fibroblast‐like cells,...
Abstract Olfactory mucosa is a source of cells for transplant‐mediated repair spinal cord injury (SCI) and currently being assessed in clinical trials. We previously reported that olfactory can generate two types sphere‐forming with stem cell‐like properties. Here we have the potential these rodent SCI model. Sphere‐forming transplanted into dorsal column integrated host cord, filling cavity, but showed no evidence differentiation vivo. Moreover, transplants supported robust axonal...
Potential protective effects of the flavonoids quercetin and luteolin have been examined against oxidative stress MC3T3-E1 osteoblast-like cells. Although hydrogen peroxide menadione reduced cell viability, toxicity was prevented by desferrioxamine or catalase but not superoxide dismutase, suggesting involvement in both cases. Quercetin damage, especially that caused peroxide. When cultures were pre-incubated with luteolin, protection lost. Protection also when a 24 h pre-incubation followed...
The mTOR is a central regulator of cell growth and highly activated in cancer cells to allow rapid tumor growth. use inhibitors as anticancer therapy has been approved for some types tumors, albeit with modest results. We recently reported the synthesis ICSN3250, halitulin analogue enhanced cytotoxicity. report here that ICSN3250 specific inhibitor operates through mechanism distinct from those described previous inhibitors. competed displaced phosphatidic acid FRB domain mTOR, thus...
Abstract Background Debate has been ongoing on the relative merits of olfactory ensheathing cells (OECs) and Schwann as candidates for transplant-mediate repair CNS lesions. Both glial exhibit similar molecular cellular properties to date there no antigenic marker identified that can clearly distinguish two cell types. This inability between types prevents confirmation a controversial statement cultures OECs are contaminated with cells. Recently, proteomic analysis foetal adult an...
Notch signalling regulates neural stem cell (NSC) proliferation, differentiation and survival for the correct development functioning of central nervous system. Overactive Notch2 has been associated with poor prognosis aggressive brain tumours, such as glioblastoma multiforme (GBM). We recently reported that constitutive expression intracellular domain (N2ICD) enhances proliferation gliogenesis in NSCs. Here, we investigated mechanism by which promotes resistance to apoptosis NSCs cytotoxic...
The surgically induced remission of liver disease represents a model to investigate the signalling processes that trigger development nonalcoholic steatohepatitis with aim identifying novel therapeutic targets. We recruited patients severe obesity or without and obtained plasma samples before after laparoscopic sleeve gastrectomy for immunoblotting, immunocytochemical, metabolomic, transcriptomic epigenetic analyses. Functional studies were performed in HepG2 cells primary hepatocytes....
Immunohistochemistry is a powerful technique that widely used in biomedical research and clinics; it allows one to determine the expression levels of some proteins interest tissue samples using color intensity due biomarkers with specific antibodies. As such, immunohistochemical images are complex their features difficult quantify. Recently, we proposed novel method, including first separation stage based on non-negative matrix factorization (NMF), achieved good results. However, this method...
High mobility group (HMG) proteins are chromatin regulators with essential functions in development, cell differentiation and proliferation. The protein HMG20A is predicted by the AlphaFold2 software to contain three distinct structural elements, which we have functionally characterized: i) an amino-terminal, intrinsically disordered domain transactivation activity; ii) HMG box higher binding affinity for double-stranded, four-way-junction DNA than linear DNA; iii) a long coiled-coil domain....