- Neurobiology and Insect Physiology Research
- Hippo pathway signaling and YAP/TAZ
- Developmental Biology and Gene Regulation
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
- Ubiquitin and proteasome pathways
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cellular Mechanics and Interactions
- Cancer-related gene regulation
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Invertebrate Immune Response Mechanisms
- Wnt/β-catenin signaling in development and cancer
- Axon Guidance and Neuronal Signaling
- Protein Tyrosine Phosphatases
- Proteoglycans and glycosaminoglycans research
- Orthodontics and Dentofacial Orthopedics
- Protein Kinase Regulation and GTPase Signaling
- Temporomandibular Joint Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- HER2/EGFR in Cancer Research
- Dental Anxiety and Anesthesia Techniques
- PI3K/AKT/mTOR signaling in cancer
- CRISPR and Genetic Engineering
Institute for Research in Biomedicine
2017-2024
Institute for Research in Biomedicine
2024
Universitatea de Medicină, Farmacie, Științe și Tehnologie „George Emil Palade” din Târgu Mureș
2022
Centro de Biología Molecular Severo Ochoa
2006-2021
Universidad Autónoma de Madrid
2006-2021
Consejo Superior de Investigaciones Científicas
2010-2013
Laminins are heterotrimeric molecules found in all basement membranes. In mammals, they have been involved diverse developmental processes, from gastrulation to tissue maintenance. The Drosophila genome encodes two laminin alpha chains, one beta and Gamma, which form distinct trimers. So far, only mutations affecting or other trimer analysed. order study embryonic development the complete absence of laminins, we mutated gene encoding sole chain Drosophila, LanB1, so that no trimers can be...
Dorsal closure (DC) of the Drosophila embryo is a model for study wound healing and developmental epithelial fusions, involves sealing hole in epidermis through migration epidermal flanks over tissue occupying hole, amnioserosa. During DC, cells at edge migrating extend Rac- Cdc42-dependent actin-based lamellipodia filopodia from their leading (LE), which exhibits breakdown apicobasal polarity as adhesions are severed with neighbouring amnioserosa cells. Studies using mammalian have...
Signaling by Smoothened (Smo) plays fundamental roles during animal development and is deregulated in a variety of human cancers. Smo transmembrane protein with heptahelical topology characteristic G protein-coupled receptors. Despite such similarity, the mechanisms regulating signaling are not fully understood. We show that Gprk2, Drosophila member receptor kinases, key role signal transduction pathway. Lowering Gprk2 levels wing disc reduces expression targets causes phenotype reminiscent...
Abstract The extracellular signal‐regulated kinase (ERK) is a key transducer of the epidermal growth factor receptor (EGFR) and fibroblast (FGFR) signaling pathways, its function required in multiple processes during animal development. activity ERK depends on phosphorylation state conserved threonine tyrosine residues, this regulated by different kinases phosphatases. A family phosphatases with specificity toward both residues (dual‐specificity phosphatases) play role dephosphorylation...
The non-visual ß-arrestins are cytosolic proteins highly conserved across species that participate in a variety of signalling events, including plasma membrane receptor degradation, recycling, and signalling, can also act as scaffolding for kinases such MAPK Akt/PI3K. In Drosophila melanogaster, there is only single ß-arrestin, encoded by kurtz, whose function essential neuronal activity. We have addressed the participation Kurtz during development imaginal discs, epithelial tissues...
The formation of the Drosophila wing involves developmental processes such as cell proliferation, pattern formation, and differentiation that are common to all multicellular organisms. genes controlling these cellular behaviors conserved throughout animal kingdom, genetic analysis development has been instrumental in their identification functional characterization. is a postembryonic structure, most loss-of-function mutations lethal homozygous flies before metamorphosis. In this manner,...
Ewing sarcoma (EwS) is a cancer that arises in the bones and soft tissues, typically driven by Ewing’s breakpoint region 1-Friend leukemia virus integration 1 (EWS-FLI) oncogene. Implementation of genetically modified animal models EwS has proved difficult largely owing to EWS-FLI’s high toxicity. The EWS-FLI 1FS frameshift variant circumvents toxicity but still able perform key oncogenic functions provided first study model Drosophila . However, quest for lines expressing full-length,...
Abstract The Drosophila genome contains approximately 14,000 protein-coding genes encoding all the necessary information to sustain cellular physiology, tissue organization, organism development, and behavior. In this manuscript, we describe in some detail phenotypes adult fly wing generated after knockdown of 80% genes. We combined phenotypic description with a comprehensive molecular classification proteins into classes that summarize main expected or known biochemical/functional aspect...
The regulation of Extracellular regulated kinase (Erk) activity is a key aspect signalling by pathways activated extracellular ligands acting through tyrosine transmembrane receptors. In this process, participate proteins with that phosphorylate and activate Erk, as well different phosphatases inactivate Erk de-phosphorylation. state phosphorylation affects not only its activity, but also subcellular localization, defining the repertoire target proteins, consequently, cellular response to...
Using transgenic RNAi technology, we have screened over 4000 genes to identify targets inhibit malignant growth caused by the loss of function lethal(3)malignant brain tumour in Drosophila vivo . We identified 131 targets, which belong a wide range gene ontologies. Most these target are not significantly overexpressed mbt tumours hence showing that, rather counterintuitively, tumour-linked overexpression is good predictor functional requirement. Moreover, found that most upregulated remain...
Drosophila l(3)mbt malignant brain tumors present sexual dimorphism.
Abstract We have screened a collection of UAS-RNAi lines targeting 10,920 Drosophila protein-coding genes for phenotypes in the adult wing. identified 3653 (33%) whose knockdown causes either larval/pupal lethality or mutant phenotype affecting formation normal The most frequent consist changes wing size, vein differentiation, and patterning, defects margin apposition dorsal ventral surfaces. also defined 16 functional categories encompassing relevant aspect each protein function assigned...
Activation of Ras signaling occurs in ~30% human cancers. However, activated alone is insufficient to produce malignancy. Thus, it imperative identify those genes cooperating with driving tumoral growth. In this work, we have identified a novel EGFR inhibitor, which named EGFRAP , for daptor p rotein. Elimination potentiates Ras-induced overgrowth the Drosophila wing imaginal disc. We show that interacts physically phosphorylated form via its SH2 domain. expressed at high levels regions...
AbstractGain of function screens have being frequently used to search for genes affecting a particular adult character or developmental process. These experiments are made possible by the adoption Gal4/UAS system flies, and design P elements bearing UAS sequences. We recently published two in which large number newly generated P-UAS insertions were crossed with Gal4 drivers expressed pupal veins central region wing disc. From data obtained these other screens, it seems that gain-of-function...
Gain-of-function screens in Drosophila are an effective method with which to identify genes that affect the development of particular structures or cell types. It has been found a fraction 2-10% tested, depending on particularities screen, results discernible phenotype when overexpressed. However, it is not clear what extent gain-of-function generated by overexpression informative about normal function gene. Thus, very few reports attempt correlate loss- and for collections identified...
Ewing sarcoma (EwS) is a human malignant tumor typically driven by the sarcoma-Friend leukemia integration (EWS-FLI) fusion protein. A paucity of genetically modified animal models, partially owed to high toxicity EWS-FLI, hinders research on EwS. Here, we report spontaneous mutant variant, EWS-FLI1FS, that circumvents issue in Drosophila. Through proteomic and genomic analyses, show EWS-FLI1FS interacts with Drosophila homologues EWS-FLI protein partners, including core subunits chromatin...