A5072821349- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Head and Neck Cancer Studies
- BRCA gene mutations in cancer
- Lung Cancer Treatments and Mutations
- Polyomavirus and related diseases
- Biological Research and Disease Studies
- Plant Disease Resistance and Genetics
- Aldose Reductase and Taurine
- Plant Virus Research Studies
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Biochemical effects in animals
- Cancer-related Molecular Pathways
- Acute Lymphoblastic Leukemia research
- Genetic factors in colorectal cancer
- Microtubule and mitosis dynamics
- Nanowire Synthesis and Applications
- Histone Deacetylase Inhibitors Research
- Cardiac Ischemia and Reperfusion
- Plant Genetic and Mutation Studies
- Protist diversity and phylogeny
- Genomic variations and chromosomal abnormalities
- Adolescent and Pediatric Healthcare
Hospital La Paz Institute for Health Research
2022-2024
Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas
2020-2024
Universidad Autónoma de Madrid
2020-2024
Centro de Investigación Biomédica en Red
2018-2024
Instituto de Salud Carlos III
2020-2024
Spanish National Cancer Research Centre
2024
Hospital Universitario La Paz
2022-2024
Hospital de Sant Pau
2018-2022
Centre for Biomedical Network Research on Rare Diseases
2015-2022
Universitat Autònoma de Barcelona
2013-2021
Toll-like receptors (TLRs) engage networks of transcriptional regulators to induce genes essential for antimicrobial immunity. We report that NFAT5, previously characterized as an osmostress responsive factor, regulates the expression multiple TLR-induced in macrophages independently osmotic stress. NFAT5 was induction key gene Nos2 (inducible nitric oxide synthase [iNOS]) response low and high doses TLR agonists but is required Tnf Il6 mainly under mild stimulatory conditions, indicating...
Adoptive T cellular immunotherapies have emerged as relevant approaches for treating cancer patients who relapsed or become refractory (R/R) to traditional treatments. Chimeric antigen receptor (CAR) T-cell therapy has improved survival in various hematological malignancies. However, significant limitations still impede the widespread adoption of these therapies most cancers. To advance this field, six research groups created “NEXT Generation CART MAD Consortium” (NEXT CART) Madrid’s...
BRCA1 is a tumor suppressor that regulates DNA repair by homologous recombination. Germline mutations in are associated with increased risk of breast and ovarian cancer deficient tumors exquisitely sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. Therefore, uncovering additional components this pathway extreme importance for further understanding development therapeutic vulnerabilities. Here, we identify EDC4, known component processing-bodies regulator mRNA decapping, as member...
Abstract Purpose: Fanconi anemia rare disease is characterized by bone marrow failure and a high predisposition to solid tumors, especially head neck squamous cell carcinoma (HNSCC). Patients with HNSCC are not eligible for conventional therapies due toxicity in healthy cells, predominantly hematotoxicity, the only treatment currently available surgical resection. In this work, we searched validated two already approved drugs as new potential patients anemia. Experimental Design: We...
The transcription factor NFAT5/TonEBP regulates the response of mammalian cells to hypertonicity. However, little is known about physiopathologic tonicity thresholds that trigger its transcriptional activity in primary cells. Wilkins et al. recently developed a transgenic mouse carrying luciferase reporter (9xNFAT-Luc) driven by cluster NFAT sites, was activated calcineurin-dependent NFATc proteins. Since site this very similar an optimal NFAT5 site, we tested whether could detect activation...
Abstract Cyclosporin A (CsA) and FK506 suppress T cell activation by inhibiting calcineurin the calcineurin-dependent transcription factors nuclear factor of activated cells (NFAc), which are central regulators function. It was reported that CsA up-regulated transforming growth factor-β1 (TGF-β1) in lymphocytes other its promoter A549 lung carcinoma cells, but mechanisms involved poorly understood, it is unclear whether plays any role. We have studied regulation TGF-β1 normal human lines. In...
Abstract Fanconi anemia (FA) is characterized by chromosome fragility, bone marrow failure (BMF) and predisposition to cancer. As reverse genetic mosaicism has been described as “natural gene therapy” in patients with FA, we sought evaluate the clinical course of a cohort FA mosaic followed at referral centers Spain over 30‐year period. This includes majority T cells without chromosomal aberrations DEB‐chromosomal breakage test. Relative non‐mosaic patients, observed higher proportion adult...
Fanconi anemia (FA) patients frequently develop oral squamous cell carcinoma (OSCC). This cancer in FA is diagnosed within the first 3-4 decades of life, very often preceded by lesions that suffer a malignant transformation. In addition, they respond poorly to current treatments due toxicity or multiple recurrences. Translational research on new chemopreventive agents and therapeutic strategies has been unsuccessful partly scarcity disease models failure fully reproduce disease. Here we...
Fanconi anaemia (FA) is an inherited disorder characterized by chromosomal instability. The phenotype variable, which raises the possibility that it may be affected other factors, such as epigenetic modifications. These play important role in oncogenesis and pharmacologically manipulated. Our aim was to explore whether profiles FA differ from non-FA individuals these could manipulated alter disease phenotype. We compared expression of genes DNA methylation profile tumour suppressor between...
Fanconi anemia (FA) is the most prevalent inherited bone marrow failure (BMF) syndrome. Nevertheless, pathophysiological mechanisms of BMF in FA have not been fully elucidated. Since cells are defective DNA repair, we hypothesized that hematopoietic stem and progenitor (HSPCs) might express damage-associated stress molecules such as natural killer group 2 member D ligands (NKG2D-Ls). These could then interact with activating NKG2D receptor expressed cytotoxic NK or CD8+ T cells, which may...
Abstract Fanconi anemia (FA) is a rare genetic disease characterized by high phenotypic and genotypic heterogeneity, extreme chromosome fragility. To better understand the natural history of FA, identify risk prognostic factors, develop novel therapeutic strategies, Spanish Registry Patients with FA collects data on clinical features, fragility, subtypes, DNA sequencing informed consent participating individuals. In this article, we describe evolution 227 patients followed up for to 30...
Abstract Background Fanconi anemia is a rare disease clinically characterized by malformations, bone marrow failure and an increased risk of solid tumors hematologic malignancies. The only therapies available are hematopoietic stem cell transplantation for or leukemia, surgical resection tumors. Therefore, there still urgent need new therapeutic options. With this aim, we developed novel high-content cell-based screening assay to identify drugs with potential in FA. Results A TALEN-mediated...
BRCA2 is essential for homologous recombination DNA repair. mutations lead to genome instability and increased risk of breast ovarian cancer. Similarly, in BRCA2-interacting proteins are also known modulate sensitivity damage agents established cancer factors. Here we identify the tumor suppressor CDK5RAP3 as a novel helical domain-interacting protein. depletion induced resistance, single-strand annealing upregulation, reduced spontaneous damage-induced genomic instability, suggesting that...
About 40% of RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients undergoing anti-EGFR-based therapy have poor outcomes. Treatment failure is not only associated with poorer prognosis but higher healthcare costs. Our aim was to identify novel somatic genetic variants in the primary tumor and assess their effect on anti-EGFR response.Tumor (somatic) blood (germline) DNA samples were obtained from two well-defined cohorts mCRC patients, those sensitive resistant EGFR blockade....
Relapsed and refractory (R/r) disease in paediatric acute leukaemia remains the first reason for treatment failure. Advances molecular characterisation can ameliorate identification of genetic biomarkers strategies this disease, especially high-risk patients. The purpose study was to analyse a cohort R/r children diagnosed with lymphoblastic (ALL) or myeloid (AML) order offer them targeted if available. Advanced 26 patients performed using NGS, MLPA, RT-qPCR. clinical relevance identified...
<div>AbstractPurpose:<p>Fanconi anemia rare disease is characterized by bone marrow failure and a high predisposition to solid tumors, especially head neck squamous cell carcinoma (HNSCC). Patients with Fanconi HNSCC are not eligible for conventional therapies due toxicity in healthy cells, predominantly hematotoxicity, the only treatment currently available surgical resection. In this work, we searched validated two already approved drugs as new potential patients...
<p>Figure S6. Additional data on gefitinib and afatinib toxicity analysis in WT Fanca-deficient mice.</p>
<p>Figure S7. Additional data on gefitinib and afatinib toxicity analysis in WT Fanca-deficient mice.</p>