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Functional characterization of alpha-synuclein non-human primate models – SUMMA
Trillions of gut microbes to rescue AED: the microbiome associated to clinical response in children epilepsy – TrilliAED
The TrilliAED project’s objectives are to i) demonstrate the link between the human microbiome and response to AED in children, ii) unravel the microbiome in early-life and its role in AED response, iii) define why and how specific microbiomes may sustain or boost AED efficacy, lowering adverse even
A therapeutic wound dressing technology to prevent early osteoarthritis development following traumatic knee injuries – ARTiTHERA
Trauma is one of the most important risk factors for osteoarthritis. Repairing osteochondral lesions soon after the trauma could prevent or delay the onset of osteoarthritis. Unfortunately, there is a dramatic lack of solutions for this repair. ARTiTHERA project concerns the implementation and eva
Exploring the P-glycoprotein-mediated efflux transport at the blood-brain barrier as a biomarker of drug-resistance in focal epilepsy – EPIFLUX
Epilepsy is one of the most common serious neurological disorders, affecting approximately 65 million people worldwide. Seizures can be controlled by antiepileptic drugs (AEDs) in most cases. However, ~30% of patients have drug-resistant epilepsy (DRE) and experience debilitating refractory seizures
Application of a Bioelectronic-electroporation Lesion Ablation to target Temporal lobe Epilepsy – ABLATE
Epilepsy is a neurological disorder characterized by spontaneous and recurrent seizures. This disease is widespread throughout the world but in some cases remains very difficult to treat. It is recognized that 30% of patients are drug-resistant, so in many cases the only possible approach is surgica
Targeting Glutamine Metabolism to prevent Diabetic Cardiovascular Complications – GlutaDiab
We hypothesize that targeting glutamine-dependent pathways in monocytes/macrophages may limit the inflammatory phenotype and CV events in diabetes. We will test this hypothesis using the combination of unique human studies, mouse models and genome-wide molecular and epigenomic analyses to dissect t
Alcohol-related neurodevelopmental disorders: imaging and modelling markers from the brain anatomy – ANDIMBA
Alcohol-related neurodevelopmental disorders are a leading cause of cognitive and behavioral disability, still under recognized in our country, partly due to the lack of specificity of the fetal alcohol spectrum disorder (FASD) clinical diagnosis in the absence the whole malformative features of fet
Basophils in Lupus: Mechanisms and Therapy – BALUMET
Systemic Lupus Erythematosus (SLE) is a rare autoimmune disease characterized by autoreactive antibodies (autoAb) mainly raised against nuclear antigens. These autoAb will form some immune complexes that will deposit in target organs where they induce inflammatory flares that can ultimately lead to
Identification of a proteomic signature in blood and gut that correlates with islet-beta cell function recovery. – BariMice
Type 2 diabetes is a chronic disease characterized by a central obesity, an insulin resistance and a reduction of insulin secretion. Bariatric surgery is an important tool for the discovery of novel therapeutic targets for restoring beta-cell function. We have validated and published a bariatric sur
Decreasing ganglioside synthesis as a therapy for hereditary spastic paraplegia – TREATSPG11
Hereditary spastic paraplegias (HSP) are a group of rare neurodegenerative diseases characterized by motor dysfunction, and also cognitive impairment in some severe forms of the disease. Currently, the only available treatments are symptomatic, and do not prevent or delay the disease progression. Th
Pre-clinical research for diseases caused by IM dysfunction. – IMprove
The KCNQ2 gene encodes the Kv7.2 subunit of the potassium Kv7/M channel, known to control neuronal excitability in the brain and spinal chord via the M current (IM). Pathogenic variants in the KCNQ2 gene represent the major cause of early onset epileptic encephalopathy, leading to the concept of KCN
"Toxic" microbiome and progression of Chronic Kidney Disease. A prospective study – CKD_Microbiome
Chronic kidney disease (CKD) affects 10 to 15% of the adult population and is associated with high risks of progression to end-stage kidney disease (ESKD), cardiovascular disease and mortality. Few treatments are currently available to slow CKD progression and reduce its complications. The compositi
Propagation and toxicity of pathogenic determinants of amyotrophic lateral sclerosis – SPREADALS
Amyotrophic lateral sclerosis (ALS) is a fatal and incurable paralytic neurodegenerative disorder caused by the loss of motoneurons in the brain and spinal cord. ALS is the third most frequently diagnosed neurological disorder after Alzheimer’s and Parkinson’s disease. Each year, ALS is responsible
Improve maternal healing through recruitment of foetal progenitors – NatStem
In all mammals, foetal cells are transferred during pregnancy to the mothers. These foetal microchimeric cells (FMC) (a) persist in low amounts in maternal bone marrow for decades after delivery, (b) are well tolerated by the maternal immune system, (c) harbor progenitor cells and (d) are able to mi
Deciphering the self-antigen specific T cell signature of autoimmune liver diseases – DISTAL
There are three major autoimmune liver diseases (AILD): autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Around thirty thousand persons are affect by one of the three AILD in France with three thousand new cases per year. They are characterized
Development of a novel biotherapy targeting inflammatory pathways in Netherton syndrome – TARGET-NS
Netherton Syndrome (NS) is an orphan genetic skin disease causing severe skin inflammation and scaling. We previously identified SPINK5 (serine protease inhibitor Kazal type 5) encoding LEKTI as being the defective NS gene. We recently identified by comparative mRNA sequencing, increased expression
Modeling follicular lymphoma in chicken embryos to personalize therapeutic decision – FLINOVO
Follicular lymphoma (FL) is the most frequent indolent lymphoma. Even if the overall survival is prolonged for the majority of the patients, a fraction of them does not respond well to first line treatment and has a poor prognosis. However, current prognostic tools are not robust enough to identify
In silico models of drug transport to enhance personalized medicine – IMOTEP
The IMOTEP (In silico MOdels of drug Transport to Enhance Personalized medicine) research project aims at building in silico molecular models of key pharmacological events of the patient response to multidrug treatments. A series of six human membrane transporters (solute carrier - SLC - and ATP-bin
IL-3 axis as a target to inhibit basophils in inflammatory conditions – BASIN
Atopic diseases cause major morbidity and economic loss. Although rare immune cells, basophils are implicated in the pathogenesis of allergic diseases of respiratory system and skin (including rhinitis, asthma and atopic dermatitis), and also autoimmune and other inflammatory diseases like bullous p
identifying GENetic factOrs influencing the development of VAScular aneurysms in autosomal dominant Polycystic Kidney Disease – GENOVAS-PKD
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, with an estimated prevalence of ~1 in 1000 to 1 in 2500 individuals. Its course is characterized by the development of multiple kidney cysts, causing progressive loss of kidney function and frequently
Digestive fistula therapy by extracellular vesicles delivered into a thermoresponsive hydrogel – FisTher
Fistulas are a major neglected health burden related to Crohn's disease or secondary to surgery, cancer therapy or trauma. Post-surgical digestive fistulas are challenging conditions associated with low remission rates and high refractoriness. There is an urgent need of novel therapeutic approaches
Fundamental, genetic and clinical aspects of male infertility due to severe sperm flagellar abnormalities – FLAGEL-OME
The first four tasks of our project correspond to different approaches converging towards a single goal: to identify and characterize most actors of flagellogenesis. We will use two different models, the mouse and Trypanosoma brucei, to validate new genes and perform proteomic analyses to identify p
Rho GTPases in rare cutaneous diseases – RIDES
Small GTPases of the Rho family, their regulators and their effectors assemble molecular platforms at the surface of membranes that control multiple signaling pathways. These signaling platforms are involved in various physiological functions and processes in the cell, such as the regulation of the
primary Antibody ImmunoDeficiencies: genetics and pathophysiological mechanism – AID
This project intends to study the molecular, genetic and pathophysiological mechanisms leading to primary antibody deficiencies (PADs). A detailed understanding of the precise molecular pathophysiological mechanism is essential to develop novel knowledge-based treatment strategies. Genetic delineati
Functional metabolic mapping of neuronal activation using magnetic resonance – fMETAMR
In this new approach, we use the chemical exchange saturation transfer (CEST) technique in order to allow: (i) the imaging of glucose levels in the brain at rest with high spatial resolution and (ii) the dynamic imaging of glucose changes during neuronal activation, taking advantage of the high temp
Autophagy Deficiency in innate immune cells in a paradigm of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – AD-ME
The contrast between the huge number of vaccinated people and the low rate of MMF detection suggests that some individuals have difficulty to clear out the adjuvant from their innate immune cells. We previously uncovered SNPs in autophagy genes in ME/CFS patients with MMF. Indeed, preliminary data (
Individual muscle Coordination strategies and their role in the development of musculoskeletal disorders – COMMODE
Our primary testable hypothesis is that each individual has unique muscle coordination strategies that will have specific mechanical effects on his/her MSK system. As such, some strategies would make people more at risk of developing MSK disorders than others. This hypothesis was presented in an inv
Gene editing therapeutics for LMNA cardiomyopathy – Correct-LMNA
Dilated cardiomyopathy, a myocardial disorder defined by ventricular chamber enlargement and systolic dysfunction, is the second leading cause of advanced heart failure, accounting for almost 50% of all heart transplantations. In about 25-50% of patients with dilated cardiomyopathy, monogenic causat
Magnetic Signal detection of ventricular arrhythmogenic substrates – Maestro
Ventricular arrhythmias are a major cause of sudden cardiac death in Europe (350,000 deaths / year). The majority of these deaths cannot be anticipated and prevented due to the low sensitivity of current risk criteria. Cardiac mapping of surviving patients has shown the presence of distinctive elect
Stroke-induced Myocardial dysfunction: role of GDF-15 – SMOG-15
Acute stroke may induce dramatic alterations of cardiovascular function and even may increase myocardial vulnerability to ischemia-reperfusion injury. However, few works have explored this cross-talk between the brain and heart during ischemic processes and the role of new effective biomarkers in co
Targeting the vitamin D receptor for the treatment of rare diseases induced by calcitriosis – VARaD
High circulating levels of vitamin D (calcitriosis) lead to hypercalcemia, and are a hallmark of several rare refractory pediatric disorders. Among them, idiopathic infantile hypercalcemia type I (IIH1), induced by CYP24A1 biallelic mutations, is one of the most frequent diagnosed chronic calcitrios
LYMPHOCYTES: SUPERVISORS OF MICROGLIAL ACTIVATION AND REMYELINATION in MUTIPLE SCLEROSIS PATIENT. – SMARTinMS
In multiple sclerosis (MS), the extent and efficacy of remyelination is highly variable among patients and this variability determines patient disability accrual. The burden of innate immune cells activation, measured by positron emission positron emission tomography (PET), was also recently showed
Translational research in Neonatal intensive care units about Staphylococcus Capitis: from molecular characterization to clinical implications in practice – NeoSCap
Preterm birth represents the leading cause of death in children under 5 year-old throughout the world and is responsible for numerous complications. Among these complications, nosocomial late-onset sepsis (LOS, defined as sepsis occurring after 3 days of life) is highly frequent in neonatal intensiv