A5024925583- 3D Printing in Biomedical Research
- Cancer Cells and Metastasis
- Cellular Mechanics and Interactions
- NF-κB Signaling Pathways
- Ubiquitin and proteasome pathways
- Wnt/β-catenin signaling in development and cancer
- 14-3-3 protein interactions
- interferon and immune responses
- Axon Guidance and Neuronal Signaling
- Tissue Engineering and Regenerative Medicine
- Signaling Pathways in Disease
- Cell death mechanisms and regulation
- Planarian Biology and Electrostimulation
- Hydrogels: synthesis, properties, applications
- Cell Adhesion Molecules Research
- Skin and Cellular Biology Research
- Single-cell and spatial transcriptomics
- Electrowetting and Microfluidic Technologies
- Inflammasome and immune disorders
- DNA Repair Mechanisms
- Cancer-related gene regulation
- Hippo pathway signaling and YAP/TAZ
- Microfluidic and Bio-sensing Technologies
- Retinoids in leukemia and cellular processes
- Immune Response and Inflammation
Institute for Bioengineering of Catalonia
2018-2025
Universitat de Barcelona
2022-2023
University of Cologne
2011-2016
Institut d'Investigació Biomédica de Bellvitge
2006-2016
Institut Català d'Oncologia
2006-2016
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2011-2016
Hospital del Mar Research Institute
2009-2012
Barcelona Biomedical Research Park
2012
Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading activation and contribution of pathway colorectal cancer is not yet understood. By microarray analysis, we have identified a group genes downstream Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by (repressed gamma-secretase inhibitors up-regulated active Notch1 in absence beta-catenin signaling). We demonstrate Wnt cells through beta-catenin-mediated...
Abstract Intestinal organoids have emerged as a powerful in vitro tool for studying intestinal biology due to their resemblance vivo tissue at the structural and functional levels. However, sphere-like geometry prevents access apical side of epithelium, making them unsuitable standard assays designed flat cell monolayers. Here, we describe simple method formation epithelial monolayers that recapitulates -like type composition organization is suitable barrier assays. In our approach,...
Nuclear functions for IkappaB kinase (IKK), including phosphorylation of histone H3 and nuclear corepressors, have been recently described. Here, we show that IKK is activated in colorectal tumors concomitant with the presence phosphorylated SMRT (silencing mediator retinoic acid thyroid hormone receptor) corepressor aberrantly localized cytoplasm. In these tumors, IKKalpha associates to chromatin specific Notch targets, leading release SMRT. Abrogation activity by BAY11-7082 or expressing...
Abstract The tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF-κB, MAP kinase and Wnt signalling. However, the suppressing mechanisms of remain poorly understood. Here we show that loss catalytic activity causes impaired DNA damage-induced p53 stabilization activation in epithelial cells sensitizes mice chemical carcinogen-induced intestinal skin tumorigenesis. Mechanistically, interacts with deubiquitinates facilitating its response genotoxic stress. Ubiquitin...
Mounting evidence supports the importance of intestinal epithelial barrier and its permeability both in physiological pathological conditions. Conventional vitro models to evaluate rely on formation tightly packed monolayers grown hard substrates. These two-dimensional lack cellular mechanical components non-epithelial compartment barrier, stroma, which are key contributors vivo. Thus, advanced approaching vivo tissue composition fundamental improve precision drug absorption predictions,...
Intestinal epithelial cells are segregated into proliferative crypts and differentiated regions. This organization relies on specific signals, including Wnt3a, which regulates cell proliferation within crypts, Eph/Ephrin, dictates positioning along the crypt-villus axis. However, studying how spatial distributions of these signals influences is challenging both in vitro vivo. Here we show that micropatterns Wnt3a can govern size, shape long-range vitro. By adjusting spacing between ligand...
Nuclear IKKα regulates gene transcription by phosphorylating specific substrates and has been linked to cancer progression metastasis. However, the mechanistic connection between tumorigenesis activity remains poorly understood. We have now analyzed 288 human colorectal samples found a significant association presence of nuclear IKK malignancy. Importantly, nucleus tumor cells contains an active isoform with predicted molecular weight 45 kDa (p45-IKKα) that includes kinase domain but lacks...
IkappaB are responsible for maintaining p65 in the cytoplasm under non-stimulating conditions and promoting active export of from nucleus following NFkappaB activation to terminate signal. We now show that 14-3-3 proteins regulate signaling pathway by physically interacting with IkappaBalpha proteins. identify two functional binding domains protein involving residues 38-44 278-283, map interaction region 60-65. Mutation these or results a predominantly nuclear distribution both TNFalpha...
AbstractWe have previously shown that IKKs are aberrantly activated in colon cancer cells leading to SMRT phosphorylation and its release from the chromatin. We now show IKKα phosphorylates homologous N-CoR corepressor serines 2345 2348 creating a functional 14-3-3 binding domain (RKpS2348KSP). Moreover, we analyzed subcellular localization of 43 colorectal samples found aberrant cytoplasmic distribution is general trait these tumors.
The stiffness and topography of a cell's extracellular matrix (ECM) are physical cues that play key role in regulating processes determine cellular fate function. While substrate can dictate cell differentiation lineage, migration, self-organization, topographical features change the profile or migration ability. Although both present intrinsic to native tissues vivo, vitro studies have been hampered by lack technological set-ups would be compatible with culture characterization. In...
Topographical patterns are a powerful tool to study directional migration. Grooved substrates have been extensively used as in vitro models of aligned extracellular matrix fibers because they induce cell elongation, alignment, and migration through phenomenon known contact guidance. This process, which involves the orientation focal adhesions, F-actin, microtubule cytoskeleton along direction grooves, has primarily studied on hard materials non-physiological stiffness. But how it unfolds...
Abstract Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial–mesenchymal transition (pEMT), proliferation, and further redifferentiation into specialized tubule epithelial cells (TECs). Because the immunosuppressant cyclosporine-A produces pEMT in TECs inhibits peptidyl-prolyl isomerase (PPIase) activity cyclophilin (Cyp) proteins, we hypothesized that cyclophilins could regulate TEC phenotype. Here demonstrate cultured TECs, CypA...
Gradients of signaling pathways within the intestinal stem cell (ISC) niche are instrumental for cellular compartmentalization and tissue function, yet how they sensed by epithelium is still not fully understood. Here a new in vitro model small intestine based on primary epithelial cells (i), apically accessible (ii), with native mechanical properties controlled mesh size (iii), 3D villus-like architecture (iv), precisely biomolecular gradients ISC (v) presented. Biochemical formed through...
Abstract Eph‐ephrin signaling acts as spatial cue to define the tissue boundaries, axonal growth, or organization of compartmentalized tissues in vertebrates. By regulation tension, adhesion, and repulsion, intermingling cells expressing membrane‐tethered ligand receptor is prevented. Despite being surface‐bound, most studies addressing interactions use soluble ligands, which lack component needed study patterning. Here, it shown that patterns ephrin ligands can modulate different...
Developing protocols to obtain intestinal epithelial monolayers that recapitulate in vivo physiology overcome the limitations of organoids' closed geometry has become great interest during last few years. Most developed culture models showed physiological-relevant cell composition but did not prove self-renewing capacities. Here, we show a simple method mouse small intestine-derived organized into proliferative crypt-like domains, containing stem cells, and differentiated villus-like...
Gradients of signaling pathways within the intestinal stem cell (ISC) niche are instrumental for cellular compartmentalization and tissue function, yet how they sensed by epithelium is still not fully understood. Here we present a new in vitro model small intestine based on primary epithelial cells (i), apically accessible (ii), with native mechanical properties controlled mesh size (iii), 3D villus-like architecture (iv), precisely biomolecular gradients ISC (v). Biochemical formed through...
Abstract Directional migration is involved in multiple physiological and pathological processes. Among other external signals, the architecture of extracellular matrix can trigger directed cell through a phenomenon known as contact guidance: cells elongate, align, migrate along direction set by aligned fibers. This process involves orientation focal adhesions, actin, tubulin cytoskeleton those Contact guidance has been extensively studied on stiff materials with topographical grooved...
Abstract Intestinal epithelial migration is supposed to occur in a passive manner driven by the mitotic pressure exerted either cryptal stem cells, under physiological conditions, or newly formed epithelium, upon damage. However, whether interactions between different neighboring cell types and with matrix contribute movement remain elusive. Here, we developed novel three-dimensional vitro intestinal mucosa model of gap closure, that includes both epithelium basement membrane cellular...