A5036682854- Bioinformatics and Genomic Networks
- Protein Kinase Regulation and GTPase Signaling
- Hippo pathway signaling and YAP/TAZ
- Cancer Genomics and Diagnostics
- Wnt/β-catenin signaling in development and cancer
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Cancer-related gene regulation
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Radiomics and Machine Learning in Medical Imaging
- 3D Printing in Biomedical Research
- Cancer Cells and Metastasis
- Chronic Myeloid Leukemia Treatments
- Cellular transport and secretion
- Cell death mechanisms and regulation
- Cellular Mechanics and Interactions
- T-cell and Retrovirus Studies
- Hair Growth and Disorders
- Biomedical Text Mining and Ontologies
- Machine Learning in Healthcare
- Protein Tyrosine Phosphatases
- NF-κB Signaling Pathways
- Cell Adhesion Molecules Research
- Gene expression and cancer classification
Universidad de Salamanca
2017-2025
Centro de Investigación del Cáncer
2017-2025
École Polytechnique Fédérale de Lausanne
2021-2025
Centro de Investigación Biomédica en Red de Cáncer
2017-2025
Instituto de Salud Carlos III
2018-2025
Consejo Superior de Investigaciones Científicas
2018-2024
Bioengineering (Switzerland)
2024
Three-dimensional organoid culture technologies have revolutionized cancer research by allowing for more realistic and scalable reproductions of both tumour microenvironmental structures
With the advent of OMICs technologies, both individual research groups and consortia have spear-headed characterization human samples multiple pathophysiologic origins, resulting in thousands archived genomes transcriptomes. Although a variety web tools are now available to extract information from data, their utility has been limited by capacity nonbioinformatician researchers exploit information. To address this problem, we developed CANCERTOOL, web-based interface that aims overcome major...
Organoid tumor models have emerged as a powerful tool in the fields of biology and medicine such 3D structures grown from cells recapitulate better characteristics, making these tumoroids unique for personalized cancer research. Assessment their functional behavior, particularly protein secretion, is significant importance to provide comprehensive insights. Here, label-free spectroscopic imaging platform presented with advanced integrated optofluidic nanoplasmonic biosensor that enables...
Macrophage metalloelastase or matrix metalloproteinase-12 (MMP12) is a macrophage-specific proteolytic enzyme involved in the physiopathology of many inflammatory diseases, including bowel disease. Although previously published data suggested that modulation MMP12 macrophages could be determinant for development intestinal inflammation, scarce information available on mechanisms underlying regulation expression those phagocytes. Therefore, this study, we aimed to delineate association with...
R-RAS2/TC21, a member of the R-RAS subfamily GTP-binding proteins, shares structural and signaling properties with RAS proteins H-, K-, N-RAS. However, little information is available regarding its role in normal cells level functional redundancy classical proteins. In this work, we used loss gain-of-function approaches to assess these issues mouse embryonic fibroblasts (MEFs). Using primary MEFs from Rras2–/–, Rras–/– or Rras–/–; Rras2–/– embryos, show here that endogenous R-RAS2/TC21...
Rho guanine exchange factors (GEFs), the enzymes that stimulate GTPases, are deemed as potential therapeutic targets owing to their protumorigenic functions. However, understanding of spectrum pathobiological roles in tumors is still very limited. We report here GEF Vav1 unexpectedly possesses tumor-suppressor functions immature T cells. This function entails noncatalytic nucleation complexes between ubiquitin ligase Cbl-b and intracellular domain Notch1 (ICN1) favors ICN1 ubiquitinylation...
Abstract Regenerative proliferation capacity and poor differentiation are histological features usually linked to prognosis in head neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show those traits can be triggered by RHO GTPase activator VAV2 keratinocytes present skin oral mucosa. is also required maintain hnSCC patient-derived cells. This function, which both catalysis- GTPase-dependent, mediated c-Myc- YAP/TAZ-dependent...
Abstract Skeletal muscle promotes metabolic balance by regulating glucose uptake and the stimulation of multiple interorgan crosstalk. We show here that catalytic activity Vav2, a Rho GTPase activator, modulates signaling output IGF1- insulin-stimulated phosphatidylinositol 3-kinase pathway in tissue. Consistent with this, mice bearing Vav2 protein decreased exhibit reduced mass, lack proper insulin responsiveness and, at much later times, syndrome-like condition. Conversely, expressing...
RAS GTPases are frequently mutated in human cancer. H- and NRAS isoforms distributed over both plasma-membrane endomembranes, including the Golgi complex, but how this organizational context contributes to cellular transformation is unknown. Here we show that at selectively activated by apoptogenic stimuli antagonizes cell survival suppressing ERK activity through induction of PTPRκ, which targets CRAF for dephosphorylation. Consistently, contrast what occurs plasma-membrane, cannot induce...
Using Sos1 knockout (Sos1-KO), Sos2-KO, and Sos1/2 double-knockout (Sos1/2-DKO) mice, we assessed the functional role of Sos2 in skin homeostasis under physiological and/or pathological conditions. depletion resulted significant alterations homeostasis, including reduced keratinocyte proliferation, altered hair follicle blood vessel integrity dermis, adipose tissue hypodermis. These defects worsened significantly when both were absent. Simultaneous disruption led to severe impairment ability...
Abstract VAV2 is an activator of RHO GTPases that promotes and maintains regenerative proliferation-like states in normal keratinocytes oral squamous cell carcinoma (OSCC) cells. Here, we demonstrate also regulates ribosome biogenesis those cells, a program associated with poor prognosis human papilloma virus-negative (HPV − ) OSCC patients. Mechanistically, this process catalysis-dependent manner using conserved pathway comprising the RAC1 RHOA GTPases, PAK ROCK family kinases, c-MYC...
Abstract Skin integrity requires constant maintenance of a quiescent, yet responsive, population stem cells. While interfollicular epidermal progenitors control normal homeostasis, hair follicle cells residing within the bulge provide regenerative potential during cycle and in response to wounding. The aryl hydrocarbon receptor (AhR) modulates cell plasticity differentiation its overactivation results severe skin lesions humans. However, physiological role homeostasis growth is unknown....
Article7 October 2021Open Access Source DataTransparent process Cancer-associated mutations in VAV1 trigger variegated signaling outputs and T-cell lymphomagenesis Javier Robles-Valero orcid.org/0000-0001-5218-0187 Molecular Mechanisms of Cancer Program, Centro de Investigación del Cáncer, CSIC-University Salamanca, Spain Instituto Biología y Celular Biomédica en Red Cáncer (CIBERONC), Search for more papers by this author Lucía Fernández-Nevado orcid.org/0000-0002-1757-6650 L Francisco...
The bidirectional regulation of epithelial–mesenchymal transitions (EMT) is key in tumorigenesis. Rho GTPases regulate this process via canonical pathways that impinge on the stability cell-to-cell contacts, cytoskeletal dynamics, and cell invasiveness. Here, we report GTPase activators Vav2 Vav3 utilize a new Rac1-dependent miR-200c-dependent mechanism maintains epithelial state by limiting abundance Zeb2 transcriptional repressor breast cancer cells. In parallel, Vav proteins engage...
Abstract Although the advent of organoids opened unprecedented perspectives for basic and translational research, immune system-related remain largely underdeveloped. Here we established from thymus, lymphoid organ responsible T cell development. We identified conditions enabling thymic epithelial progenitor proliferation development into with in vivo-like transcriptional profiles diverse populations. Contrary to two-dimensional cultures, maintained thymus functionality vitro mediated...
Although the advent of organoids has opened unprecedented perspectives for basic and translational research, immune system-related remain largely underdeveloped. Here, we established from thymus, lymphoid organ responsible T-cell development. We identified conditions enabling mouse thymic epithelial progenitor cell proliferation development into with diverse populations transcriptional profiles resembling in vivo cells (TECs) more closely than traditional TEC cultures. In contrast to these...
The mevalonate pathway plays an important role in breast cancer and other tumor types. However, many issues remain obscure as yet regarding its mechanism of regulation action. In the present study, we report that expression enzymes is mediated by RHO guanosine nucleotide exchange factors VAV2 VAV3 a RAC1‐ sterol regulatory element‐binding factor (SREBF)‐dependent manner cells. Furthermore, vivo tumorigenesis experiments indicated two most upstream steps this metabolic...
Multiple crosstalk between peripheral organs and the nervous system are required to maintain physiological metabolic homeostasis. Using Vav3-deficient mice as a model for chronic sympathoexcitation-associated disorders, we report here that afferent fibers of hepatic branch vagus nerve needed development sympathoexcitation, tachycardia, tachypnea, insulin resistance, liver steatosis adipose tissue thermogenesis present in those mice. This neuronal pathway contributes proper activity rostral...
Prior reports showed the critical requirement of Sos1 for epithelial carcinogenesis, but specific functionalities homologous and Sos2 GEFs in skin homeostasis tumorigenesis remain unclear. Here, we characterize mechanistic roles played by or primary mouse keratinocytes (a prevalent cell lineage) under different experimental conditions. Functional analyses actively growing relevant genotypes—WT, Sos1-KO, Sos2-KO, Sos1/2-DKO—revealed a role regarding transcriptional regulation control RAS...