Pamplona, Spain

University of Navarra
Pamplona, Spain

The University of Navarra is a private pontifical university based at the southeast border of Pamplona, Spain. It was founded in 1952 by St. Josemaría Escrivá de Balaguer, the founder of Opus Dei, as a corporate work of the apostolate of Opus Dei.Through its six campuses , the University confers 35 official degrees, 13 double degrees and more than 38 master programs in 14 faculties, 2 university schools, 17 institutes, its graduate business school, IESE , ISSA , and other centers and institutions.The university also runs a teaching hospital CUN, where 2,045 qualified professionals handle more than 100,000 patients each year, and medical research centre, CIMA, that focuses on four main areas: Oncology, Neuroscience, Cardiovascular science, and Gene Therapy and Hepatology.In 2012, the New York Times ranked the University of Navarra's IESE within Top 50 Universities in the world, placing it at number 34. Wikipedia.

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French National Center for Scientific Research and University of Navarra | Date: 2017-05-17

The invention relates to a modified bacterium belonging to the Brucella genus that carries an inactivated wadC gene and an inactivated ppdK gene and to uses thereof. The invention also relates to a vaccine against brucellosis in human and/or animals comprising a modified bacterium belonging to the Brucella genus that carries an inactivated wadC gene and an inactivated ppdK gene.

Agency: European Commission | Branch: H2020 | Program: IA | Phase: SCC-01-2014 | Award Amount: 34.64M | Year: 2015

GrowSmarter aims to: Improve the quality of life for European citizens by better mobility, housing and the quality of urban infrastructure while improving the citizens economy by lower energy costs and creating as much as 1500 new jobs (on the demonstration level). Reduce the environmental impact by lower energy needs by 60 % and increased use of renewable energy thus reducing GHG emissions even more. Create sustainable economic development by demonstrating and preparing a wider rollout of smart solutions. GrowSmarter will demonstrate at 3 lighthouse cities 12 smart, integrated solutions as a way of preparing for a wider market rollout. These solutions are integrated in specially chosen sites making demonstration easy to reach and take part of for the 5 follower cities and other European and international study groups. All the smart solutions are fit into the Lighthouse-cities strategic development plans and the follower cities replication plans. The solutions solve common urban challenges such as: Renewal of existing buildings. GrowSmarter demonstrates the cost efficient renewal of 100.000 square meters of Nearly Zero or low energy districts reducing energy demand by 70-90%, Integrated infrastructures for ICT, street lighting, smart grids district heating and smarter waste handling Sustainable urban mobility for both passenger and gods integrated in smart grids, biofuels from household waste thus reducing local air quality emissions by 60%. The integration of Cities, strong group of industrial partners together and quality research organisations guarantee that the solutions will be both validated by independent research organisations and transformed into Smart Business Solutions by industry for the wider rollout to Europe. Growsmarter builds on integrated, close to the market solutions, to form business models for their wider deployment by the industrial partners. The project will help Europe GrowSmarter!

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 7.57M | Year: 2015

Immune responses are initiated by antigen presentation mediated by dendritic cells (DC). There is a minority subset of DC highly specialised in starting up cytotoxic T lymphocytes able to kill tumor cells. PROCROP aims to develop in three pilot clinical trials a suitable individualized cancer vaccine technology for castration resistant prostate cancer and metastatic cancer of the ovary that would complement currently available therapies to increase efficacy. The project applies recent compelling knowledge on the identity of the main antigen-presenting DC subsets for vaccine elicitation of cytotoxic T lymphocytes endowed with the ability to seek and destroy tumour cells (such immune mechanism is termed crosspriming). This unique opportunity for superior DCs for immunotherapy comes from the fact that Miltenyi, a successful European biotech company, has the necessary proprietary reagents (anti-BDCA-3 monoclonal antibody and immunomagnetic selection technology), as well as the expertise to clinically develop a strategy of DC isolation and short-term cell culture for immunotherapy. From the point of view of the tumor antigens, processed autologous tumor material will be mixed with defined common tumor antigens in the form of recombinant proteins. This novel combination will permit stronger and broader antitumor immune responses and more accurate monitoring of the ensuing immunity against the tumors. These features should make the novel DC vaccine more efficacious than the currently US-approved DC vaccine PROVENGE and other DCs preparations undergoing trials, such as those derived from monocytes. Three of the leading groups in immunotherapy of cancer in Europe would join forces to develop this individualized cell therapy technology in clinical trials for two highly prevalent and unsatisfactorily managed malignant conditions. Industrial partnership provides the unique advantage of producing a rigorously standardized product for eventual multicentre trials.

Agency: European Commission | Branch: H2020 | Program: IA | Phase: INNOSUP-1-2015 | Award Amount: 5.04M | Year: 2016

The overall concept of the project consist of supporting innovation in SMEs and fostering the smart reindustrialization of Europe by enabling the emergence of new cross-border and cross-sectoral value chains resulting from the translation of advanced technologies among selected sectors with strong synergies. These new value chains will be created from the interaction of the following sectors: aerospace,agro-food sector, Health & medical devices and ICT. The project will take of 36Months. The development of the new value chains will be facilitated setting up geographical poles of activitiy in different regions across ES, PT,NL, IL and PL, comprising: Cluster/ SME intermediaries, which help create an appropriate innovation ecosystems;RTD centres. which are able to assess the potential and viability of the proposed new value chains for SMEs innovative services or products. Besides, a third kind of entity, theinnovation facilitatorswill operate at a cross-cluster level, organizing funding rounds to complement with private funds EU public support and establishing networks for collaboration. More than 50 letters of support signed by different type of stakeholders. ACTTiVAte will undertake 2 kind of activities to optimize the benefits to SMEs:a)Direct funding of SMEs innovative projects. Competitive calls will be launched in the proposed technology areas.Thewining projects (30)will receive an amount of up to 50.000 each from a total of a 1,5M from the project budget. The selection criteria will consider both the technical feasibility and viability and the socioeconomic impact. Investment rounds will be organized to raise private funding to multiply the effect of public investment.b)Activities aimed at creating a favourable environment for the innovation in SMEs, such as brockerage events, mentoring, coaching, mobility and exchange programs among other initiatives. The demonstration of the project at large scale will also be carried out during the project.

The World Health Organisation (WHO) has included low back pain in its list of twelve priority diseases. Notably, Degenerative disc disease (DDD) presents a large, unmet medical need which results in a disabling loss of mechanical function. Today, no efficient therapy is available. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated degeneration of adjacent segments. Our consortium partners have developed and studied stem cell-based, regenerative therapies with encouraging results in phase 1 and 2a trials. Patients exhibited rapid and progressive improvement of functional and pain indexes by 50% within 6 months and by 65% to 78% after 1 year with no side effects. In addition, MRI T2 relaxation measurements demonstrated a significant improvement. To develop the worlds first rigorously proven, effective treatment of DDD, RESPINE aims to assess, via a multicentre, randomized, controlled, phase 2b clinical trial including 112 patients with DDD, the efficacy of an allogenic intervertebral mesenchymal stem cell (MSC)-based therapy. This innovative therapy aims to rapidly (within 3 months) and sustainably (at least 24 months) reduce pain and disability. In addition, the consortium aims to provide new knowledge on immune response & safety associated with allogeneic BM-MSC intradiscal injection. This simple procedure would be cost-effective, minimally invasive, and standardised. The transfer to the clinic will be prepared at a cost below 10k thanks to the strategy of production of allogenic cells, automation & EU standardisation. At the end of the RESPINE trial, we aim to propose a broadly available and clinically applicable treatment for DDD, marketed by European SMEs.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: LCE-01-2016-2017 | Award Amount: 4.61M | Year: 2016

Flexibility needs to be added to Europes power system to accommodate an increasing share of variable power generation from renewable sources. Indeed, service quality issues start to arise on the grid when this share in electricity consumption reaches 10%. To meet the EUs targets for reduction of greenhouse gas emissions this share should rise to 30% by 2030 and up to 50% by 2050. The cost of this transition and the necessary measures to guarantee stable and continuous supply are a major political concern. The SABINA project responds to it by targeting the cheapest possible source of flexibility: the existing thermal inertia in buildings and the coupling between heat and electricity networks it enables. This coupling requires accurately estimating the thermal inertia of many buildings. SABINAs partner the University of Navarra has created a breakthrough, automatic method for this estimation, which shall be scaled up, validated and integrated in a complete management system through this project. This system will operate on two complementary time horizons: One day: aggregation and management at the district level of the electric and thermal flexibilities, and conversion and storage of the excess electrical energy to thermal energy in the freely available building inertia. Seconds to minutes: local control of inverters feeding renewable electricity to the grid, with optimal parameters automatically determined at the district level. Research partners will develop novel control and optimization algorithms, and integrate and evaluate the system in lab and operational settings. The SABINA solution is compatible with both new and existing buildings; it is planned to be deployed within five years of the end of the project. Lead users are present in the consortium: Telvent and SMS plc, the coordinator, for the architecture, and Insero for the business model it enables; compliance and contribution to relevant standards will be ensured by the European Digital SME Alliance

Conde-Alvarez R.,University of Navarra
PLoS pathogens | Year: 2012

Innate immunity recognizes bacterial molecules bearing pathogen-associated molecular patterns to launch inflammatory responses leading to the activation of adaptive immunity. However, the lipopolysaccharide (LPS) of the gram-negative bacterium Brucella lacks a marked pathogen-associated molecular pattern, and it has been postulated that this delays the development of immunity, creating a gap that is critical for the bacterium to reach the intracellular replicative niche. We found that a B. abortus mutant in the wadC gene displayed a disrupted LPS core while keeping both the LPS O-polysaccharide and lipid A. In mice, the wadC mutant induced proinflammatory responses and was attenuated. In addition, it was sensitive to killing by non-immune serum and bactericidal peptides and did not multiply in dendritic cells being targeted to lysosomal compartments. In contrast to wild type B. abortus, the wadC mutant induced dendritic cell maturation and secretion of pro-inflammatory cytokines. All these properties were reproduced by the wadC mutant purified LPS in a TLR4-dependent manner. Moreover, the core-mutated LPS displayed an increased binding to MD-2, the TLR4 co-receptor leading to subsequent increase in intracellular signaling. Here we show that Brucella escapes recognition in early stages of infection by expressing a shield against recognition by innate immunity in its LPS core and identify a novel virulence mechanism in intracellular pathogenic gram-negative bacteria. These results also encourage for an improvement in the generation of novel bacterial vaccines.

Circulating myeloma tumor cells (CTCs) as defined by the presence of peripheral blood (PB) clonal plasma cells (PCs) are a powerful prognostic marker in multiple myeloma (MM). However, the biological features of CTCs and their pathophysiological role in MM remains unexplored. Here, we investigate the phenotypic, cytogenetic, and functional characteristics as well as the circadian distribution of CTCs vs paired bone marrow (BM) clonal PCs from MM patients. Our results show that CTCs typically represent a unique subpopulation of all BM clonal PCs, characterized by downregulation (P < .05) of integrins (CD11a/CD11c/CD29/CD49d/CD49e), adhesion (CD33/CD56/CD117/CD138), and activation molecules (CD28/CD38/CD81). Fluorescence in situ hybridization analysis of fluorescence-activated cell sorter-sorted CTCs also unraveled different cytogenetic profiles vs paired BM clonal PCs. Moreover, CTCs were mostly quiescent and associated with higher clonogenic potential when cocultured with BM stromal cells. Most interestingly, CTCs showed a circadian distribution which fluctuates in a similar pattern to that of CD34(+) cells, and opposite to stromal cell-derived factor 1 plasma levels and corresponding surface expression of CXC chemokine receptor 4 on clonal PCs, suggesting that in MM, CTCs may egress to PB to colonize/metastasize other sites in the BM during the patients' resting period.

Sagardoy A.,University of Navarra
Blood | Year: 2013

B-cell maturation and germinal center (GC) formation are dependent on the interplay between BCL6 and other transcriptional regulators. FOXP1 is a transcription factor that regulates early B-cell development, but whether it plays a role in mature B cells is unknown. Analysis of human tonsillar B-cell subpopulations revealed that FOXP1 shows the opposite expression pattern to BCL6, suggesting that FOXP1 regulates the transition from resting follicular B cell to activated GC B cell. Chromatin immunoprecipitation-on-chip and gene expression assays on B cells indicated that FOXP1 acts as a transcriptional activator and repressor of genes involved in the GC reaction, half of which are also BCL6 targets. To study FOXP1 function in vivo, we developed transgenic mice expressing human FOXP1 in lymphoid cells. These mice exhibited irregular formation of splenic GCs, showing a modest increase in naïve and marginal-zone B cells and a significant decrease in GC B cells. Furthermore, aberrant expression of FOXP1 impaired transcription of noncoding γ1 germline transcripts and inhibited efficient class switching to the immunoglobulin G1 isotype. These studies show that FOXP1 is physiologically downregulated in GC B cells and that aberrant expression of FOXP1 impairs mechanisms triggered by B-cell activation, potentially contributing to B-cell lymphomagenesis.

Agency: European Commission | Branch: H2020 | Program: ERC-STG | Phase: ERC-StG-2015 | Award Amount: 1.47M | Year: 2016

Multiple myeloma (MM) represents a unique model to investigate cancer stem cells (CSCs), circulating tumour cells (CTCs), and the mechanisms of malignant transformation and chemoresistance. Despite the substantial improvement in MM patients outcome, the vast majority of patients eventually relapse and the disease remains largely incurable. For those patients failing to achieve deep remissions, biologically targeted research on the ultra-chemoresistant minimal residual disease (MRD) clone may allow us to understand the cellular mechanisms driving chemoresistance, and design novel therapeutic to overcome; importantly, such effort should be equally performed on two additional key players: CSCs and CTCs. On the opposite side, it is unquestionable that a selected group of patients does experience long-term survival irrespectively of the depth of response achieved, but we fail to understand the mechanisms driving sustained disease control. Is it because of persistent residual benign clones? Is it because of immune surveillance? Here, we will integrate next-generation flow cytometry and sequencing to define i) the signature of CTCs and ultra-chemoresistant MRD cells, ii) the hierarchical place of putative CSCs, iii) the genomic landscape of benign vs. malignant clones; and iv) the role of immune surveillance to achieve functional cures. Hence, we will characterize for the first-time-ever the highly-professional subclones responsible for malignant transformation, disease dissemination, and dramatic relapses after optimal response to therapy. Noteworthy, the innovative approach of this scientific proposal strongly relies on the use and expertise of highly-sensitive next-generation flow cytometry, coupled with optimized DNA- and RNA-sequencing for low-cell-numbers, and prospective patient samples longitudinally available within the scope of well-controlled clinical trials. Herein, we believe that all requirements are met to conduct this ground-breaking research program.

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