Inicio > Portal de Transparencia > Información Económica. Proyectos de Investigación con financiación externa
Acciones Marie-Sklodowska-Curie

Acciones Marie-Sklodowska-Curie

MARIE CURIE ACTIONS-COFUND (MCA-COFUND)

  • Titulo: CAD_FL: Revealing the functional mechanism of CAD and its potential as a therapeutic target
  • Referencia: 608765
  • Investigador Principal: Moreno Morcillo, María
  • Resumen

    Pyrimidine nucleotides are essential building blocks for DNA or RNA synthesis. In mammals, two possible routes entail the production of pyrimidines: nucleotides can be recycled by salvage pathways or synthesized de novo from small metabolites. In general, the activity of the latter is low in resting or fully
    differentiated cells but indispensable in proliferating cells. Thus, in tumour and neoplastic cells the de novo pyrimidine biosynthesis is invariably up-regulated in order to cover the elevated requirement of nucleic acids precursors. Pyrimidine biosynthesis through this pathway is initiated and controlled by CAD,
    a multifunctional protein that assembles into hexamers of ~1.5 MDa and catalyses the first three reactions of the process. Recently, the host laboratory determined the crystal structures of two fragments of human CAD, the DHO and ATC domains, the latter isolated or bound to the anti-tumoral drug PALA. These two pieces are of great interest but insufficient to understand the puzzling structure/function of the entire CAD particle, which contains two additional uncharacterized regions, the GLN and CPS domains. This project aims to decipher the structure of full-length CAD and to understand the catalytic and regulatory
    mechanisms that controls the biosynthesis of pyrimidines. The acquired knowledge will be used for rational design of compounds that could potentially modulate the activity of this multifunctional complex with the prospect of developing new and more potent anti-tumoral drugs.

  • Fecha Inicio: 01/04/2015
  • Fecha Fin: 31/03/2018
  • Presupuesto Otorgado: 87.343,80 €
  • Fuente de Financiación: WHRI-ACADEMY PROGRAMME. 7 FRAMEWORK PROGRAMME ( 2007-2013 )

MARIE CURIE ACTIONS-COFUND (MCA-COFUND)

  • Titulo: ADIPOMET: Analyzing the crosstalk of tumor and adipose tissue during metastasis
  • Referencia: 608765
  • Investigador Principal: Peinado Selgas, Héctor
  • Resumen

    Over the past several decades, incidences of overweight and obesity have been rising very rapidly. Similarly, the prevalence of malignant cancers is also rising in nearly all countries. Obesity has been associated to the increased risk to develop metastasis in certain cancers such as melanoma, colon, breast and ovary. It is necessary to understand the biological processes linking obesity to tumor progression. Metastasis is associated with poor prognosis in most of the cancer types; approximately 15–20% of melanoma patients will develop metastasis. Our preliminary results suggest that exosomes secreted by melanoma cells serve as novel communication mechanism between the tumor and the adipose tissue. In this proposal we plan, #1, to visualize and characterize the mechanism of exosome crosstalk between tumor cells and adipocytes. This will be followed by detailed studies of the functional consequences regulating melanoma invasion and metastasis. We will expand these studies with a detailed lipidomic analysis of adipocyte secretome during melanoma metastasis. #2 we will build on preliminary results showing that adiponectin levels in circulating exosomes are reduced in stage IV melanoma patients. After determining the contribution melanoma to downregulate the expression of adiponectin in the adipose tissue we will follow with experiments to determine what factor(s) regulate adiponectin secretion and the mechanism(s) by which adiponectin affects invasion and metastasis. We ultimately aim to generate the signatures of circulating exosomes in melanoma patients. We will correlate the number of circulating exosomes with BMI and metastatic risk determining lipidomic signatures to build rational therapies that can interfere with the metabolic pathways regulated during metastasis.

  • Fecha Inicio: 01/01/2016
  • Fecha Fin: 31/12/2018
  • Presupuesto Otorgado: 87.343,80 €
  • Fuente de Financiación: WHRI-ACADEMY PROGRAMME. 7 FRAMEWORK PROGRAMME ( 2007-2013 )

MARIE CURIE ACTIONS-COFUND (MCA-COFUND)

  • Titulo: STEM-PSO: Unraveling the contribution of Epidermal and Non-Epidermal Progenitor cells in the development of Psoriasis
  • Referencia: 608765
  • Investigador Principal: Gago López, Nuria
  • Resumen

    Skin is one of the most regenerative organs in adult mammals. Normal skin is a self-renewal tissue that maintains homeostasis due to the presence of epidermal progenitor cells (EPC). EPCs possess enormous proliferative potential, which is engaged at a slow basal rate throughout an individual’s lifespan, with upregulated cell division occurring during wound healing and some inflammatory conditions. However, the efficiency of their regenerative potential to sustain homeostasis under chronic inflammatory conditions such as psoriasis is not fully understood. In addition, whether non-epidermal progenitors (non-
    EPC) contribute to this process has not yet defined. Psoriasis is a chronic disease of unsolved pathogenesis affecting skin and joints in 1-3% of the general population. It is known EPC derived human transitamplifying (TA) keratinocytes exhibit an increased proliferation, but a reduced apoptotic rate in psoriatic
    plaques, fostering epidermal hyperproliferation and altered differentiation.
    Whether this disarray in the balance of proliferation-apoptosis stems from EPCs and derived TA keratinocytes, or is that other cells, such as non-EPCs, could potentially be recruited to psoriatic plaques and contribute to nourish the disease is unknown. Further research and the development of innovative
    approaches are therefore needed to get insight into this problem, which in addition will have a potential impact in the future design of improved molecular and cell therapies.
    The main goal of this proposal is to study the contribution of EPCs and non-EPCs in the formation of psoriatic plaques through a genetic fate-mapping approach, analyze the molecular signals involved in the uncontrolled proliferation/differentiation/apoptosis of these keratinocytes and translate these results to human patients in situ and in vitro.

  • Fecha Inicio: 01/01/2016
  • Fecha Fin: 31/12/2018
  • Presupuesto Otorgado: 87.343,80 €
  • Fuente de Financiación: WHRI-ACADEMY PROGRAMME. 7 FRAMEWORK PROGRAMME ( 2007-2013 )

MARIE CURIE ACTIONS-INDIVIDUAL FELLOWSHIP (MCA-IF)

  • Titulo: PERSMEDOMICS: Bioinformatics and Integrative Genomics for a Novel Personalized Cancer Therapy
  • Referencia: 334361
  • Investigador Principal: Al-Shahrour Núñez, Fátima
  • Resumen

    The dawn of the age of personalized cancer treatment provides the promise to identify the right drug for the individual that will greatly improve the patient’s outcome. It is well known that cancer drugs work only in small subset of patients. For many of these agents, there are putative markers of response in the literature but very few are been used in clinical practice. More importantly, new anticancer agents are targeted to specific cancer genes and are expected to be effective only in tumors in which these genes are mutated or otherwise abnormal. Consequently, the success of personalized treatment of cancer patients depends on matching the most effective therapeutic regimen with the characteristics of the individual patient, balancing benefit against risk of adverse events. The primary challenge in achieving this goal is the heterogeneity of the disease, recognizing that breast, lung, colon and the majority of cancers are not single diseases but rather an array of disorders with distinct molecular mechanisms.
    High-throughput technologies such as next-generation sequencing, gene expression microarrays have the capacity to dissect this heterogeneity and now doing an unbiased interrogation of the human genome, which allows strategies to search for novel, previously unsuspected, biomarkers of drug response and afford opportunities to match therapies with the characteristics of the individual patient’s tumor.
    Here we propose to develop an integrative bioinformatics approach as part of CNIO’s personalized cancer treatment platform that will predict treatment response and select new biomarkers based on the integration of genomics data and drug response analyzed in patients with pancreatic cancer and personalized xenografted mice. A cross-disciplinary integrative effort that will convert the information contained in multidimensional data sets into useful biomarkers that can classify patient tumors by prognosis and response to therapeutic modalities.

  • Fecha Inicio: 01/07/2013
  • Fecha Fin: 30/06/2017
  • Presupuesto Otorgado: 100.000,00 €
  • Fuente de Financiación: 7 FRAMEWORK PROGRAMME ( 2007-2013 )

MARIE CURIE ACTIONS-INDIVIDUAL FELLOWSHIP (MCA-IF)

  • Titulo: GLIDD: DNA Damage Response (DDR) signaling in tumor formation and therapeutic resistance of gliomas
  • Referencia: 618751
  • Investigador Principal: Squatrito, Massimo
  • Resumen

    The gliomas are a large group of brain tumors and Glioblastoma Multiforme (GBM) is the most common and lethal primary central nervous system (CNS) tumor in adults. Despite the recent advances in treatment modalities, GBM patients generally respond poorly to all therapeutic approaches and prognosis remain dismal. Standard therapy for GBMs includes resection of the tumor mass, followed by concurrent radiotherapy and chemotherapy, using the alkylating agent temozolomide (TMZ). Nonetheless, GBM patients remain refractory to treatment. Understanding the genetic events that lead to glioma formation and the mechanisms of resistance to therapy will be instrumental for the development of new treatment modalities for gliomas.
    Maintenance of genomic integrity is essential for embryonic development and adult tissue homeostasis. Defects in the DNA Damage Response (DDR) machinery, a network of protein complexes capable of detecting DNA lesions and signaling to downstream effector pathways (cell cycle checkpoints, DNA repair, apoptosis, etc.), are linked to numerous pathological states including brain cancers. The focus of this proposal is the identification of DDR genes involved in tumor formation and therapy resistance of gliomas. We will also investigate how the tumor microenvironment contributes to resistance to standard treatment modalities. We reason that these studies will help to define new therapeutic targets for treatment of brain tumors.

  • Fecha Inicio: 01/07/2014
  • Fecha Fin: 30/06/2018
  • Presupuesto Otorgado: 100.000,00 €
  • Fuente de Financiación: 7 FRAMEWORK PROGRAMME ( 2007-2013 )

MARIE CURIE ACTIONS-INOVATIVE TRAINING NETWORKS (MCA-ITN)

  • Titulo: ITN aDDRess: Joint training and research network on Chromatin Dynamics and the DNA Damage Response
  • Referencia: 316390
  • Investigador Principal: Fernández Capetillo, Óscar
  • Resumen

    DNA is tightly wrapped around histones to form chromatin, a highly dynamic structure that can adopt different conformations with contrasting degrees of compaction. Essential processes of DNA metabolism, such as DNA repair, replication or transcription operate in the context of chromatin and higher order chromosomal organization. Understanding how modulation of chromatin structure and repair influence cell fate decisions in development and disease or how genome surveillance factors interact with the chromatin structure to safeguard the genome is an emerging question that represents a major challenge for human health. The objectives of the aDDRess ITN are: 1. to establish a European research platform of excellence in the proposed field, 2. to create a Network dedicated for the training of ESR/ERs promoting their independent careers and prospects and 3. to transform our current collaborations into a stronger intellectual and training network with links to the industry. In addressing these aims, we have put forward a multidisciplinary approach to study this central thematic area at the molecular, cellular and systems level by assembling a group of scientists with cross disciplinary expertise and capabilities. This integrated approach is likely to provide a solid groundwork on genome maintenance and chromatin dynamics driven by DNA damage.

  • Fecha Inicio: 01/10/2012
  • Fecha Fin: 30/09/2016
  • Presupuesto Otorgado: 3.804.294,12 €
  • Fuente de Financiación: 7 FRAMEWORK PROGRAMME ( 2007-2013 )

MARIE SKLODOWSKA CURIE ACTIONS-INOVATIVE TRAINING NETWORKS (MSCA-ITN)

  • Titulo: INMUTRAIN: Training Network for the Immunotherapy of Cancer
  • Referencia: 641549
  • Investigador Principal: Soengas, Maria Soledad
  • Resumen

    In the European Union, cancer is the leading cause of death and the overall cancer incidence is still increasing. As a result of expanding efforts to improve cancer outcome, a main paradigm change is occurring in cancer therapy towards individualized medicine. Antibody-based therapies form an integral and constantly growing part of this approach. Antibody-based therapies will strongly influence the coming decade of cancer care. The importance of immunotherapy has been highlighted by the prestigious Science journal as “breakthrough of the year 2013”, heralding the rising importance of immunotherapy. Accordingly the need for well-trained and skilled researchers in academia and industry is dramatically increasing in this field. IMMUTRAIN is a training network bringing together experts in the fields of monoclonal antibodies, dendritic cells, T-cells and immunomodulatory nucleic acids with a considerable industrial involvement. The network comprises nine academic research groups and five industrial partners in a total of seven European countries. IMMUTRAIN will actively create synergies between those sectors by forming and promoting young researchers to match the challenges of immunotherapies. Particular focus will be placed on combinatorial therapies and on the new emerging field of bispecific antibodies used to target both the tumor and the patient´s immune system. Fifteen Ph. D. students (early stage researchers, ESR) reinforced by the project leaders will investigate innovative therapeutic strategies and provide the rationale for future clinical trials. Throughout their projects, ESR will learn to integrate academic and industrial aspects and will sharpen their experimental and complementary skills in a well-designed and diversified training program.

  • Fecha Inicio: 13/06/2016
  • Fecha Fin: 12/06/2019
  • Presupuesto Otorgado: 3.627.525,24 €
  • Fuente de Financiación: HORIZON 2020 ( 2014-2020 )