Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : SaveHER (Horizon 2020, appel 2017, Proof of concept grants)
Entité participante : University of Turku — Pays : Finlande — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

HER2+ breast cancers are an aggressive type of breast cancer and have a poor prognosis. There are many therapies currently on the market to target this type of cancer, however they fail to deliver effective clinical results due to therapy resistance. In our ERC-CoG project, we found that proper endosomal trafficking is required for functional HER2 oncogenic signalling at the plasma membrane. Targeting HER2 endosomal traffic can result in effective treatment of HER2+ cancers, without the risk of therapy resistance. As such, this innovation could deliver the first truly effective cancer treatment for HER2+ breast cancer patients that do not respond to current treatments. In this ERC-PoC, we aim to prove that therapeutic targeting of endosomal traffic is effective in HER2+ cancer models in vivo, as a monotherapy and synergistically with current therapeutic antibodies, and to explore the commercial avenues to exploit this finding.

Mots-clés : breast cancer,her2,targeted therapy,drug resistance
Projet ERC : HY-NANO (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Physical and analytical chemical sciences
Entité participante : University of Pavia — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPV
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499084.0 €

HY-NANO focuses on one of the current major challenges in Europe: a global transition to a low-carbon society and green economy by 2050. Solar energy can lead a “paradigm shift” in the energy sector with a new low-cost, efficient, and stable technology (3-pillars strategy). Nowadays, low-cost three dimensional (3D) Hybrid Perovskites (HP) solar cells are revolutionizing the photovoltaic scene, with stunning power conversion efficiency beyond 22%. However, poor device stability (due to degradation in contact with water) and dependence on toxic components (lead) substantially hamper their commercialization. HY-NANO aims to realize a new low-cost and efficient hybrid solar technology combining long-term stability with a reduced environmental impact. Design and engineering innovative multi-dimensional hybrid interfaces is the core idea. This will be achieved by: 1. design and characterization of new stable and eco-friendly perovskites structures, with tunable composition and dimensionality ranging from 3D to 2D; 2. exploiting new synergistic functions by combining 3D and 2D perovskites together into novel stable and efficient multi-dimensional interfaces while addressing the interface physics therein; 3. integrating the hybrid interfaces into high efficient and stable device architectures engineered “ad hoc”. In addition, I propose the development of new solar cell encapsulant using metal-organic frameworks (MOFs) functionalized as selective lead receptors to minimize the environmental risks associated with the potential release of lead. My multidisciplinary expertise in advanced material design, cutting-edge photophysical experimental investigations, and solar cell engineering will enable me to successfully target the ambitious goals. HY-NANO is timely and it will generate the new fundamental knowledge that is urgently needed for a scientific and technological breakthrough in materials and devices for near future photovoltaics.

Mots-clés : hybrid perovskites,photovoltaic materials,solar cell,interface physics,charge dynamics,ultrafast spectroscopy,device engineering
Projet ERC : HALODRUGSYN (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Universität Innsbruck — Pays : Autriche — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1425986.8 €

Halogenated arenes and heteroarenes have become essential structural motifs of the pharmaceutical industry to create novel drugs against bacterial infections and cancer, and constitute highly valuable functional units in chemistry. Current methods for the installation of carbon-halogen bonds lack efficiency, selectivity, and practicability within the complex molecular setting of drug development processes. These restrictions prevent many potential drugs from being synthesized in a time- and cost-efficient manner. In this project, I aim to address these challenges by engineering a highly elaborated synthetic toolbox that is equipped with novel transformations of unprecedented efficiency, selectivity and practicability. I will apply these transformations to the construction of novel antibiotics against resistant strains and more efficient chemotherapeutics to combat cancer. The first objective is to establish innovative transformations that enable for the first time an efficient access to halogenated arenes. I will accomplish this goal by developing novel ring-expansion reactions and apply them to the first synthesis of the antibiotic salimabromide in order to address the acute problem of antibiotic resistance. Within the second part of this project, I will extend this unique synthetic platform to heteroarenes and establish a groundbreaking method based on carbon-fluorine bond activation. This will represent the first broadly applicable strategy to produce novel fluorinated heteroarene based anti-cancer drugs with unparalleled precision, efficiency and selectivity. Taken together, the realization of these strategies, all of which are unprecedented, provides for the first time a solution for the limitations associated with current methods. With my expertise in synthetic chemistry, which I have gained from my achievements in natural product synthesis, and an outstanding publication record in this research field, I am confident to accomplish these ambitious goals.

Mots-clés : natural products,total synthesis,halogenated molecules,ring expansion,fluorine chemistry,methodology
Projet ERC : CellProbe (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : IBM Research - Zurich — Pays : Suisse — Rôle : PI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 150000.0 €

Having developed a liquid scanning probe - microfluidic probe (MFP) - for creating spatially-defined microscale biochemical environments and microscale molecular assays within the ERC-BioProbe project, in this proof-of-concept project, - CellProbe - we seek to leverage this technology toward realization of a commercially viable single-cell analysis platform

Mots-clés : single cell analysis,spatial heterogeneity,microfluidics,multimodal analysis,liquid scanning probes
Projet ERC : 4DPrintedHeart (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Tel Aviv University — Pays : Israël — Rôle : PI
Acronyme de l'entité : TAU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Heart diseases are a major cause of death in the Western world. No sustainable regenerative therapy is currently available, and cardiac transplantation is the only treatment. However, the scarcity of matching heart donors raises the need to develop new regenerative medicine approaches. Recently, our group has shown the use of patient-specific cells and personalized hydrogels to 3D print vascularized cardiac patches. Moreover, we have developed printing technologies which allowed to print small-scale, cellularized human hearts with the major blood vessels. Despite these and other advances in the field, the premature hearts are very basic, and their ability to pump blood and function in vivo is still considered futuristic, requiring several major breakthroughs. In this proposal, I plan to go far beyond the current state-of-the-art and overcome some of the remaining challenges in the field. We will develop novel 4D printing approaches, allowing to print human cardiac patches and whole functional hearts, including ventricles, atria, pacemakers, conduction system and extensive vasculature, in high resolution. We will decipher the mechanisms underlying the maturation of the printed tissues and hearts, which are essential for the synchronous contraction and heart pumping. Functionality of the printed structures will be compared to that of native cardiac tissues and whole natural hearts by examining their reaction to chronotropic and cardiotoxic drugs, proving their additional potential to serve as reliable, predictive drug testing platforms. The printed tissues and hearts will be then heterotopically transplanted, and their anastomosis with the host blood vessels, contraction and blood pumping capabilities in vivo will be tested. Finally, we will demonstrate the ability of the printed, vascularized cardiac patches to improve heart function. Successful completion of this ambitious project will provide a sustainable regenerative therapy for a myriad of devastating maladies.

Mots-clés : regenerative medicine,3d printing of tissues,cell therapy,biomaterials
Projet ERC : inHForm (Horizon 2020, appel 2015, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Lund University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1496625.0 €

Heart failure is a leading cause of morbidity and mortality in the aging European populations. It is the end-stage of myocardial and valvular disease, arising from loss of viable or functional muscle cells in the heart. Therapy is complicated by the multitude of causes and comorbidities of heart failure. New therapeutic targets and clinical biomarkers to individually tailor therapy (‘precision medicine’) are greatly needed. This research program aims to realize the promise of precision medicine by applying an integrated proteomic, genomic and epidemiological approach to the underlying causes, mechanisms and consequences for heart failure. The program builds on unique Swedish nation-wide disease registers and large biobanks, the translational research profile of the investigator and experience in genomics, epidemiology and proteomics. The program includes five work packages: (1) comprehensive plasma protein profiling through a discovery pipeline including novel microarray-based methods and mass spectrometry in a population-based cohort of 6000 subjects and clinical cases to identify subjects at risk for heart disease (2) assessment of heritable components to outcomes in heart disease using nation-wide Swedish registers (3) genome-wide discovery of variants associated with risk of and outcomes in heart disease as well as endophenotypes for cardiac structure and function, using resequencing and DNA microarrays in large population-based cohorts including >70,000 subjects from three generations (4) expression profiling in human heart samples and a novel human cardiomyocyte strain assay to translate genomic and proteomic findings to understanding of pathophysiological mechanisms (5) evaluate the clinical importance of plasma proteins and genetic variants in >3000 clinical cases. This research program is anticipated to result in new insights into the pathophysiology of heart failure and discovery of drug targets and clinical biomarkers.

Mots-clés : cardiology,genomics,proteomics,heart failure,valvular disease,arrhythmia
Projet ERC : PV-COAT (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Liège — Pays : Belgique — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2302375.0 €

Heart valve prostheses are currently among the most widely used cardiovascular devices. To maintain enduring optimal biomechanical properties, the mechanical prostheses, based on carbon, metallic and polymeric components, require permanent anticoagulation, which often leads to adverse reactions, i.e. higher risks of thromboembolism, hemorrhage, and hemolysis. Continuing advances in heart valve prosthesis design and in techniques for implantation have improved the survival length and quality of life of patients who receive these devices. In an ongoing effort to develop a more durable and biocompatible heart valve prosthesis, researchers have used a variety of techniques to determine the suitability of given valve materials for a given implant application. In recent years, advances in polymer science have given rise to new ways of improving artificial cardiovascular devices biostability and hemocompatibility. To date, no polymer coated mechanical prosthetic heart valve exists. The present research project aims to improve the hemocompatibility and long-term in vivo performance of mechanical prosthetic heart valves by reducing contact-induced thrombosis through bioactive polymer prosthetic valve surface coating. These new coated prosthetic heart valves will be designed for hemodynamic performance and durability similar to uncoated materials, combined with a greater thromboresistance, both in vitro and in animal studies. With these promising advances, bioactive surface coated prosthetic heart valves could replace previous generation of prosthetic valves in the near future. The utmost perspective of the current project paves the way for the development of new bioactive coating for other implantable cardiovascular devices or materials.

Mots-clés : mechanical prosthetic heart valves,coating,valve thrombogenicity
Projet ERC : 2LIVEr (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : Istituti di Ricovero e Cura a Carattere Scientifico — Pays : Italie — Rôle : PI
Acronyme de l'entité : IRCCS
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 150000.0 €

Hepatitis B virus (HBV) infections remain a major public health issue worldwide. Over 350 -400 million people are chronically infected by HBV, and about 1 million people die each year from the complications of this infection (cirrhosis and hepatocellular carcinoma) with a consequent hefty economic impact on national health systems. This led the World Health Organization to recognise HBV infection as a key priority and adopt the global health sector strategy to eliminate viral hepatitis, with a target of reducing new infections by 90% and mortality by 65% by 2030. The risk of developing a chronic infection in healthy adults is due to a weaker, dysfunctional and narrowly focused CD8+ T cell response. Since the mechanisms underlying HBV persistence are not fully elucidated, current treatments (antiviral drugs and Interferon) aim to reduce the development of liver disease, while a definitive treatment for curing this infection is not yet available on the market. Within the ERC Consolidator Grant 725038 “FATE”, we recently characterized the mechanisms behind the ineffective CD8+ T cell response towards HBV, demonstrating the potential efficacy of interleukin-2 (IL-2) – a cytokine – to reactivate it, thus achieving antiviral activity. This discovery, jointly with our proprietary third-generation, self-inactivating lentiviral vectors (LVs) that allow selective hepatocellular expression of IL-2, pave the way to single-dose gene therapy-based approach, a potential functional cure against chronic hepatitis B. 2LIVEr project intends to optimize and further validate our novel therapeutic approach from both a technical and commercial standpoint, moving from TRL3 to TRL4, thus fastening the roadmap towards the market.

Mots-clés : hepatitis b virus,immunotherapy,interleukin 2,cd8  t cells,gene therapy
Projet ERC : inhibiTOR (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : University of Basel — Pays : Suisse — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and the fourth leading cause of cancer-related deaths worldwide. The multikinase inhibitor sorafenib is the only approved drug to treat HCC and on average enhances survival by three months. Thus, the efficacy of current HCC treatment options is very limited. Studies in the context of our ERC-Synergy grant revealed that sorafenib resistance correlates with upregulation of mammalian target of rapamycin complex 1 (mTORC1) signaling. The central role of mTORC1 in conferring therapy resistance suggests that effective therapy against HCC may require combination of a primary inhibitor (e.g., sorafenib) and an mTORC1 inhibitor. The mTORC1 inhibitor rapamycin and its derivatives (rapalogs) are approved for a few advanced cancers, but not for HCC. Their clinical applicability is limited by their effectiveness and safety. Rapalogs fail to completely inhibit mTORC1 as they have little effect on inhibiting phosphorylation of 4E-BP, one of the two main targets of mTORC1. Moreover, rapamycin and rapalogs also inhibit mTORC2 when chronically administered, leading to undesirable effects such as hyperglycemia, hyperlipidemia, and insulin resistance. We have established a biophysical assay to identify selective mTORC1 inhibitors with a novel, rapalog-unrelated, mechanism of action. We predict these inhibitors to be more selective, more effective, and potentially safer than mTORC1 inhibitors currently used in the clinic. In this Proof of Concept project, we aim to study the pharmacological potential of selective and efficient mTORC1 inhibition alone or in combination therapy with sorafenib to treat HCC.

Mots-clés : mtor signaling,hepatocellular carcinoma,mtorc1 inhibition,drug development,biophysical screening
Projet ERC : VALURED (Horizon 2020, appel 2018, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Individuals, Markets and Organisations
Entité participante : University of St. Gallen — Pays : Suisse — Rôle : PI
Acronyme de l'entité : HSG
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 688554.49 €

Heterogeneity and diversity are a pervasive aspect of modern societies. Differences in individuals’ preferences, needs, skills, and information are key to explain variation in individuals’ behavior and to anticipate individuals’ responses to policy changes. There is no consensus, however, about how to take these differences into account when evaluating policies. Project VALURED will reexamine this ethical challenge by characterizing the mapping between value judgments—i.e. principles of distributive justice—and redistribution policies. This mapping is tremendously important for welfare analysis and policy design. First, it associates the most desirable policy to each set of value judgments, providing an “ethical menu” to policy design. Second, it gives an ethical identity of each policy proposal, that is, it identifies the value judgments a policymaker endorses when proposing a specific policy. The main objectives of VALURED are to: 1) identify transparent and compelling value judgments that accommodate heterogeneity and diversity; 2) show the implications of these value judgments for the evaluation and design of redistribution policies; 3) characterize welfare criteria that respect individuals’ preferences and account for individuals’ differences in needs, skills, and information; 4) provide new insights for the design of income, capital, and inheritance taxation; 5) develop simple formulas that express optimal policies as a function of observable heterogeneity and ethical parameters. Project VALURED combines welfare economics with public economics. The first part deals with income taxation and addresses the ethical challenges related to individuals’ heterogeneity in preferences, needs, and skills. The second part focuses on capital taxation and addresses individuals’ differences in risk preferences and information. The third part analyses the design of inheritance taxation and addresses the social concerns for intergenerational and intragenerational equity.
Projet ERC : EMERGE (Horizon 2020, appel 2017, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Charité - Universitätsmedizin Berlin — Pays : Allemagne — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 481236.94 €

Heterogeneity within the endothelium is increasingly recognized in both normal and disease conditions, influencing vascular architecture, structure, and function. The diverse phenotypes that endothelial cells (ECs) adopt suggest substantial plasticity and indicate that heterogeneity is a core property that enables ECs to fulfill their tissue-specific tasks. However, the molecular basis for tissue-specific endothelial differentiation and heterogeneity remains largely unknown. In this project, we will study the impact of environmental context on endothelial specialization and focus on the emerging relationship between metabolism, epigenetics, and cellular differentiation. We hypothesize that organ-specific differences in endothelial metabolic state, through altered epigenetics, promote specialization and thereby contribute to heterogeneity within the vascular system. The proposal rests on the notion that many of the enzymes that erase epigenetic modifications (from DNA and histones) are exquisitely sensitive to changes in metabolism as they utilize cosubstrates that are generated by cellular metabolism. Using a combination of state-of-the-art genetics, high-resolution imaging, metabolomics, and biochemistry, we will study the role of these epigenetic mechanisms for general and organ-specific blood vessel formation (Objective I) and determine their regulation by metabolic and vascular differentiation signals (Objective II). Moreover, we will explore whether metabolic changes during obesity and aging impact the maintenance of endothelial specialization, and assess whether deregulation of metabolic-epigenetic signalling leads to endothelial malfunction and organ failure (Objective III). We trust that the knowledge gained through this project will provide a conceptual framework for understanding how environmental context can drive vascular heterogeneity and, more generally, how alterations in metabolism and nutrition might contribute to vascular-related diseases.

Mots-clés : vascular biology,angiogenesis,endothelial cells,endothelial heterogeneity,endothelial metabolism,vascular disease