Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : iBack (Horizon 2020, appel 2014, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Technical University of Munich — Pays : Allemagne — Rôle : Partner
Acronyme de l'entité : TUM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 263876.0 €

Chronic back pain is a major burden and source of disability worldwide. It is primarily attributed to biomechanical factors. In elderly patients, osteoporosis complicates the biomechanical scenario. Surgery is often required to treat instability-related pain and to restore the balance of the spine. However, when and how to perform surgery remains a highly subjective decision based on the surgeon’s experience, with 2/3 of patients experiencing prolonged pain. We recently established objective, image-based criteria for surgery outcome prediction. As an example, we were able to develop tools for routine density and fracture assessment and demonstrate that screw loosening occurs in >85% of patients with bone mineral density <92 mg/ccm. This directly influences the surgical approach in all spine surgery patients at our institution. Additionally, we improved the prediction of bone strength by advanced image post processing such as scaling indices, finite element and finite cell models. The high-level objective of iBack is to individualize therapy planning in back pain patients. We will improve in-vivo imaging and image analysis to compute individualized biomechanical models that reveal the underlying pathophysiologic process and allow personalized treatment planning and outcome prediction after spine surgery or conservative treatment. The main objectives of iBack are: (1) improving computed tomography (CT) and magnetic resonance imaging (MRI) of the spine; (2) combining sagittal balance radiographs, CT and MRI of the spine in one biomechanical multi-body simulation (MBS); (3) creating a statistical model that includes both clinical and biomechanical information to reveal interactions between the two and to predict individual treatment success probability. The results of iBack will help to better understand instability-related pain and develop personalized surgical strategies which will have major impacts on patients.

Mots-clés : chronic back pain,diagnostic imaging,magnetic resonance imaging,computed tomography,biomechanical models,finite element models,anthropometric parameters
Projet ERC : HEPCIR (Horizon 2020, appel 2014, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : The University of Texas System — Pays : Etats-Unis — Rôle : Partner
Acronyme de l'entité : UT System
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 196070.89 €

Chronic liver diseases such as liver cirrhosis and hepatocellular carcinoma (HCC) are major challenges for global health. HCC is the second leading and fastest rising cause of cancer death worldwide. The limited availability of therapeutic options reflects our poor understanding of the molecular and clinical mechanisms involved in progression of liver disease. Chronic hepatitis C virus (HCV) infection is a main risk factor for HCC. Although HCC may be avoided by addressing the underlying cause in early stage disease, strategies to prevent HCC in patients with established cirrhosis and advanced fibrosis, in which the risk of HCC persists despite treatment of the underlying cause are lacking. Indeed, even HCV cure does not eliminate the risk of HCC development when advanced fibrosis is already present. Since fibrosis/cirrhosis-driven carcinogenesis is the mechanism of HCC development common to all major etiologies, we propose to use HCV-induced liver disease as a model to decipher the pan-etiology sequence of molecular events underlying disease progression and HCC. Our own data provide solid evidence that HCV infection alters pathways implicated in liver disease progression, including cirrhosis deterioration, HCC development, and overall and liver-specific death. Thus, the molecular investigation of these pathways will identify key cell circuits for the understanding of the pathogenesis of liver disease and HCC in general, and as broadly applicable pan-etiology diagnostic and therapeutic targets. Using a novel patient-derived cell culture model system for liver disease biology combined with advanced functional genomics, novel animal models and clinical investigation, we aim to uncover the cell circuits that are of clinical relevance for liver disease progression and cancer. By providing novel targets and biomarkers for liver disease and HCC prevention, this proposal will have a marked impact on the management and prognosis of patients with liver disease and HCC.

Mots-clés : liver disease,liver cancer,hepatitis c,hepatocellular carcinoma,cellular pathways,kinases,phosphatases,viral hepatitis,drug target,biomarker,cell circuits
Projet ERC : BOOTCAMP (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Amsterdam University Medical Centers — Pays : Pays-Bas — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1647662.0 €

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Novel targeted drugs are effective, but not curative. Moreover, prolonged use is associated with development of resistance, toxicity, and high economic cost. Allogeneic stem cell transplantation, which evokes a T cell mediated response, is potentially curative yet is associated with high graft-vs-host-related mortality. Therefore, an autologous T cell-based approach, e.g. chimeric antigen receptor T cells (CAR-T), is a highly promising strategy. However, in contrast to the success of CAR-T cells in aggressive leukemia, their effect in CLL is limited owing to a largely unexplained acquired T cell dysfunction in this disease setting. I recently found that CLL cells impose a reduction in mitochondrial fitness and altered glucose metabolism on T cells, which may underlie the acquired T cell dysfunction. Lending clinical significance to this finding, I observed that the success of CAR-T treatment in CLL patients is highly associated with their mitochondrial biogenic capacity. I therefore hypothesize that improving mitochondrial fitness of CAR-T cells may offer a path to cure CLL. I aim to: 1. Characterize the molecular mechanisms of metabolic alterations in CLL-derived T cells 2. Elucidate how CLL cells reprogram T cells metabolism 3. Increase mitochondrial biogenesis and fitness in CAR-T cells to improve therapeutic efficacy To achieve these goals, I will conduct an array of complementary molecular, metabolic, and genetic assays using patient samples and a murine model of CLL. To address therapeutic potential I will study murine and human CAR-T cells in which metabolic processes will be manipulated. This project provides crucial insight into the interplay between CLL and T cells, and the underlying failure of cancer immune surveillance. This may lead to metabolism-based curative autologous T cell based therapies in CLL, which may also be relevant for other malignancies.
Projet ERC : BOOTCAMP (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Pennsylvania — Pays : Etats-Unis — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 230534.61 €

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Novel targeted drugs are effective, but not curative. Moreover, prolonged use is associated with development of resistance, toxicity, and high economic cost. Allogeneic stem cell transplantation, which evokes a T cell mediated response, is potentially curative yet is associated with high graft-vs-host-related mortality. Therefore, an autologous T cell-based approach, e.g. chimeric antigen receptor T cells (CAR-T), is a highly promising strategy. However, in contrast to the success of CAR-T cells in aggressive leukemia, their effect in CLL is limited owing to a largely unexplained acquired T cell dysfunction in this disease setting. I recently found that CLL cells impose a reduction in mitochondrial fitness and altered glucose metabolism on T cells, which may underlie the acquired T cell dysfunction. Lending clinical significance to this finding, I observed that the success of CAR-T treatment in CLL patients is highly associated with their mitochondrial biogenic capacity. I therefore hypothesize that improving mitochondrial fitness of CAR-T cells may offer a path to cure CLL. I aim to: 1. Characterize the molecular mechanisms of metabolic alterations in CLL-derived T cells 2. Elucidate how CLL cells reprogram T cells metabolism 3. Increase mitochondrial biogenesis and fitness in CAR-T cells to improve therapeutic efficacy To achieve these goals, I will conduct an array of complementary molecular, metabolic, and genetic assays using patient samples and a murine model of CLL. To address therapeutic potential I will study murine and human CAR-T cells in which metabolic processes will be manipulated. This project provides crucial insight into the interplay between CLL and T cells, and the underlying failure of cancer immune surveillance. This may lead to metabolism-based curative autologous T cell based therapies in CLL, which may also be relevant for other malignancies.
Projet ERC : MecCOPD (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Helmholtz Zentrum München — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : HMGU
Type d'entité : Recherche
Financement ERC de l'entité : 1499462.0 €

Chronic obstructive pulmonary disease (COPD), a chronic lung disease caused by polluted air, is the 4th most common cause of death worldwide. Adding to alveolar destruction, patients suffer from debilitating shortness of breath due to obstructed and fibrotic airways. Currently, this mechanical damage is considered a by-product of airway inflammation; rarely, however, do anti-inflammatory treatments slow disease progression. New therapies are urgently needed. Recent studies suggest that mechanical changes are themselves important active drivers of COPD. I developed an innovative 3D human airway disease model (Lung-Chip) and quantitative measurements of tissue mechanics to show that airway mechanical dysfunction lowers the defense against inflammation-causing pollutants, thereby enabling a viscous cycle of disease aggravation. In addition, my airway Lung-Chip can mimic COPD-like matrix properties, e.g. fibrotic stiffness, and physiological mechanics, including breathing stretch, blood flow and air flow. These advances allow me now to faithfully mimic the airway mechanical microenvironment and systematically study how mechanical factors drive COPD progression. MecCOPD aims to 1) Measure the mechanical properties of COPD airway tissue in pioneering clinically-relevant Lung Chip models using advanced light microscopy and signal processing, 2) Reveal the contribution of mechanics to disease progression by delivering COPD-mimicking mechanical cues and measuring transcriptional, structural and secreted disease markers, 3) Determine the dynamics between mechanical factors and disease markers using statistical models. This interdisciplinary and novel approach will generate fundamental insights into how mechanical factors contribute to COPD progression and will facilitate studying other chronic lung diseases such as cancer and fibrosis. Ultimately, unravelling the COPD phenotype-mechanics relationship will lead to the discovery of new disease mechanisms and drug targets.
Projet ERC : BREAK (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Biotechnology and Biosystems Engineering
Entité participante : University of Milan — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIMI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Chronic pain (CP) is a medical condition affecting around 20% of adults in Europe, characterised by an abnormal duration of pain (> 12 weeks) originally initiated by a trauma or illness. Despite significant progress, CP remains extremely hard to treat, with only one-third to two-thirds of patients reporting adequate some pain relief. This situation is even worse for neuropathic pain (NP), a specific class of CP affecting 8% of global population and whose origin mostly depend on peripheral or central nervous damage or disorder, which leads the brain to interpret as pain normally non painful stimuli. NP is difficult to treat due to the large number of entities involved (cells, genes and proteins working in synergy), which makes it hard to rapidly diagnose the exact cause of pain. Drugs targeting the central nervous system (e.g. antidepressants and opioids) provide only partial pain relief and are nonspecific, also causing side effects like addiction, and nausea, thus restraining their adoption for prolonged treatments. BREAK is the first non-invasive inhibitory optogenetic tool specifically designed for NP treatment, with potential application to the whole spectrum of CP. BREAK is composed of a drug and an optical device. The protein BLINK2 is injected in the painful area using a genetically engineered virus, and respond to a specific blue light by silencing the addressed neuron. The lamp can be kept at some distance (cm) from the skin and no implant is required. Just some minutes of treatment results in hours of pain relief, making the invasiveness of BREAK far lower than actually existing solution. A first version of BREAK has already demonstrated in in-vivo experiments on rats. During this project we plan to further develop the treatment and explore its commercial potential. In particular, leveraging from the experience of different partners, we will constitute a fruitful stakeholder network, including Academic centers, hospitals, pharma companies and investor

Mots-clés : neuropathic pain,ion channel,optogenetics
Projet ERC : SCOPE (Horizon 2020, appel 2018, Advanced grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Florence — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2185921.0 €

Chronic pain, characterized by increased sensitivity to innocuous/mild stimuli (allodynia), afflicts 25% of the European adult population. Efficacy and/or safety of analgesic medicines is limited, and the treatment of chronic pain associated with inflammation, peripheral and central neuropathies and cancer remains unsatisfactory. Thus, identification of novel targets for better and safer analgesics is a major medical need. Transient receptor potential ankyrin 1 (TRPA1) channel, expressed by a subpopulation of primary sensory neurons (nociceptors), has been proposed as a major transducer of acute pain. We have, recently, identified that TRPA1 is expressed in Schwann cells that ensheath peripheral nerve fibres. In a prototypical model of neuropathic pain (sciatic nerve ligation in mice), we discovered that Schwann cell-TRPA1 exerts a hitherto unknown role that, via amplification of the oxidative stress message, sustains neuroinflammation and chronic pain (allodynia). Thus, Schwann cells, through their own repertoire of channels and enzymes orchestrate in the injured/inflamed tissue an autocrine/paracrine signalling pathway to sustain chronic pain. The purpose of the present project is to extend this observation to other models of inflammatory, neuropathic and cancer pain to identify a general paradigm based on Schwann cell/TRPA1/oxidative stress as the pathway that sustains chronic pain. We aim also at identifying in oligodendrocytes (the Schwann cells of the brain) whether the TRPA1/oxidative stress pathway sustains pain in the central nervous system. In mouse, rat and human Schwann cells/oligodendrocytes we aim at identifying biomarkers and combine them into biosignatures predictive of the susceptibility to the development of chronic pain. We anticipate that each molecular step that entails the TRPA1/oxidative stress pathway in Schwann cell lineages is an eligible target for discovering new effective and safer medicines for the treatment of chronic pain.

Mots-clés : transient receptor potential ankyrin 1  trpa1  channel,transient receptor potential vanilloid 4  trpv4  channel,chronic pain,oxidative stress,schwann cells,oligodendrocytes,macrophages,g protein coupled receptors  gpcrs
Projet ERC : Restoring Roots (Horizon 2020, appel 2019, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Giessen — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : JLU
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2000000.0 €

Chronic pulmonary hypertension (PH) is a lethal disease characterized by the accumulation of persistently activated cell types in the pulmonary vasculature, exhibiting aberrant expression of genes driving apoptosis resistance, proliferation, inflammation and matrix remodeling. Current vasodilatory therapies for PH do not normalize these activated phenotypes. I have performed an “integromics” approach – combining epigenetic and transcriptional analyses to comprehensively elucidate the underlying molecular mechanisms. This approach provided evidence for the recapitulation of a “fetal-like” “remodeled” lung vascular phenotype, orchestrated via central lung developmental transcription factor (TF) networks with particular emphasis on TBX4, TBX5 and SOX9. Moreover, in addition to de-novo onset of this “fetal epigenetic programming” in adult PH, postnatal maintenance of such programming may underlie persistent pulmonary hypertension of the newborn (PPHN). Placing TBX4/TBX5/SOX9 at the center, I will probe this hypothesis i.e. will define their contribution to vascular remodeling processes underlying neonatal and adult PH. Studies will be performed in primary vascular cells and viable tissue slices from human/ experimental PH lungs, and various transgenic mouse lines. Furthermore, I will address the relationship among TBX4/TBX5/SOX9 in a transcription network that controls PH development using CRISPR–dCas9-activator mice. In addition, uncovering the TBX4/TBX5/SOX9-epigenetic circuitry by profiling epigenetic landscape ([sc]RNA-, ChIP-, ATAC-, MeD-, histone PTMs- seq) in both “pathological remodeling” and the loss of “physiological reverse remodeling” in PPHN, I aim to harness novel intervention strategies (locus-specific epigenetic modifications) to reverse aberrant remodeling and foster regeneration of lung vasculature. Hence, this proposal is highly innovative as it explores the hypothesis of a “developmental origin” of PH and PPHN and offers novel therapeutic strategies.

Mots-clés : pulmonary hypertension,pulmonary vascular diseases,transcription factors,epigenetics
Projet ERC : DCPOIESIS (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Life Science
Panel : Immunity, Infection and Immunotherapy
Entité participante : The Francis Crick Institute — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 2500000.0 €

Classical dendritic cells (cDCs) are leucocytes that play a key role in innate immunity as well as the initiation and regulation of T cell responses. cDCpoiesis starts with commitment of a bone marrow (BM) haematopoietic progenitor, known as the classical DC precursor (CDP), to the cDC lineage. CDPs then give rise to pre-cDCs that exit the BM via the blood and seed tissues to give rise to the two major types of fully-differentiated cDCs, the cDC1 and cDC2 subsets. The key parameters of cDCpoiesis are poorly understood. We propose to characterise the niche in which cDCs develop within the BM and to study how pre-cDCs seed tissues and establish local clones of differentiated cDC1 and cDC2. We further wish to ask how the activity of CDPs and pre-cDCs is altered following infection, inflammation or tissue damage. Finally, we want to know to what extent cDCpoiesis is affected by direct sensing of infection or cell damage by cDC precursors. All these objectives will be addressed in a mouse lineage tracing model in which cDC precursors are genetically labelled through the activity of a Cre recombinase driven by the Clec9a locus. These mice will be crossed to fluorescent protein reporter mice, including Confetti mice that allow for clonal analysis, and the appearance of labelled cDCs and cDC clones in tissues will be followed over time in the steady-state or after induction of infection or inflammation. The dependence of cDC precursor activity on specific pathogen and damage sensing pathways will be assessed by loss-of-function experiments. The interactions of cDC precursors with their BM niche will be analysed in steady-state or inflammatory conditions by visualising the cells in situ. Finally, the consequences of demand-driven cDCpoiesis for immunity will be assessed. The results from this project will lead to a greater understanding of the influence of environmental signals on cDCpoiesis and may have applications in the design of better vaccines and immunotherapies.

Mots-clés : dendritic cells,haematopoiesis
Projet ERC : SmartTap (Horizon 2020, appel 2014, Proof of concept grants)
Entité participante : University of Cyprus — Pays : Chypre — Rôle : PI
Acronyme de l'entité : UCY
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 77250.0 €

Clean drinking water is a critical resource, important for the health and well-being of all humans. Uninterrupted supply of clean drinking water is considered a human right, thus water utilities must monitor and control the water quality following strict European and national regulations. A water contamination event can have a dramatic effect on everyday life, as well as on the local economy. Unfortunately, due to the large-scale and complex nature of water distribution systems, water quality monitoring is sporadic, while contamination events may take days before they are detected. The situation is especially severe in developing countries, where water contamination problems commonly result in hospitalizations, or even deaths, and have a major impact on the quality of life. The idea of the proposed proof of concept is to develop the SmartTap system, an intelligent water quality monitoring system that uses spatial and temporal data processing techniques for monitoring the quality of water and detecting any contamination events. The SmartTap is a cyber-physical system comprised of low-cost wireless sensory devices (physical) and smart software (cyber) that are seamlessly integrated so that the software is able to compensate for any inaccuracies in the hardware. The system is suitable for large or small scale deployments, enabling a sensor network approach for providing effective water quality monitoring to consumers (homes, schools, hospitals, hotels, etc.) and water utilities. The goal is to provide real-time water quality monitoring information to consumers and utilities and to reliably detect any contamination events within 1-2 hours, compared to the current state of several days.

Mots-clés : computational intelligence,water distribution networks,fault diagnosis,event detection,cyber physical systems,water quality,contamination of drinking water,embedded systems