Search

Stroke is a neurological deficit which results from an interruption of cerebral blood flow, mainly due to the appearance of a clot that blocks a cerebral artery (ischemic stroke: 80% of cases). Such a clot has usually been formed in the upstream circulation, in the heart or in a ruptured atheroscler

Holoprosencephaly (HPE) is a common congenital brain disease; its aetiology remains too poorly understood to provide proper clinical management. Genetics is the major component of this disorder, with alterations leading to a decrease in the Sonic Hedgehog (SHH) signalling pathway. However, genetic v

Homogeneous meiotic arrest is a rare condition that prevents sperm formation or accelerated ovarian exhaustion, resulting in infertility for which there is no treatment today. Recent results confirm genetic heterogeneity, but there is currently no standardized description of the testicular phenotype

Photobiomodulation, or light therapy, slow down the neurodegenerative process in models of Parkinson's disease. Other studies illustrate that light limit some symptoms of Alzheimer's disease. Huntington's disease is a neurodegenerative disease without any treatment, and presenting several similariti

In epilepsy surgery candidates, the identification of the cortical areas to be removed and the evaluation of their functional integrity is a difficult process which often requires intracranial EEG (iEEG) recordings. However, even when using iEEG information, epilepsy surgery fails in a substantial p

Alcoholic liver disease (ALD) is the leading cause of cirrhosis worldwide with no specific therapeutic options other than alcohol withdrawal. Patients with alcohol misuse have an individual susceptibility to develop an ALD. This susceptibility, but also the severity of the ALD, depends, at least in

Chronic lung allograft dysfunction (CLAD) is the primary cause of poor-long term outcomes after lung transplantation. CLAD pathogenesis is poorly understood, and there are no effective therapies for the prevention or treatment of CLAD. It is increasingly recognised that the balance of effector and r

Crohn’ disease (CD) is a chronic disabling inflammatory bowel disease affecting around one million people in Europe. Gut inflammation results from an inappropriate immune response against intestinal microbiota occurring on a predisposed genetic background. Several genes of susceptibility have been i

The Brugada Syndrome (BrS) is an inherited arrhythmic disease suspected to be responsible for > 20% of cases of sudden cardiac death (SCD) in patients without structural heart disease. It is also suspected to be involved in 4-12% of SCD in the general population. Clinical diagnosis is based on a spe

Each year, thousands of platelet concentrates are collected, stored at most 7 days and transfused. The needs for platelets are not met, and extending their shelf-life is a major stake. Therefore, elucidating what regulates platelets lifespan is mandatory. The WrinXL project has 2 aims: (1) to pinpo

Von Willebrand disease (VWD) is an inherited rare bleeding disorder resulting from quantitative or qualitative deficiencies in von Willebrand factor (VWF), a plasma glycoprotein, crucial to platelet thrombus formation. The current VWD classification, although crucial to understand the pathophysiolog

Recently, we identified missense mutations in HAVCR2 (coding gene for TIM-3) as a genetic cause of a newly described genetic disorder characterized by hemophagocytic lymphohistiocytosis (HLH) associated to sub-cutaneous panniculitis-like T-cell lymphoma (SPTCL). HLH is a rare life-threatening condi

The loss of functional ? cells is the root cause for the development of diabetes. Therapies aimed at the replenishment of the pancreatic ? cell are among the most promising strategies to treat diabetes. In this project, we will investigate the effects of new selective Dyrk1A inhibitors developed by

The worldwide prevalence of Gestational Diabetes Mellitus (GDM) has increased steadily over the last decade, affecting up to 10.8 % of the pregnancies in France, mainly due to the rising proportion of women with pre-pregnancy overweight, sedentary lifestyle and advanced maternal age at birth. GDM fu

Bipolar disorder (BD) is a psychiatric condition characterized by depressive and manic episodes, for which diagnosis and treatment are challenging and can take several years after the first symptoms. Only 30% of the patients respond to lithium monotherapy with complete disappearance of symptoms, 10-

Acute ischemic stroke (AIS) is a public health issue because of its poor functional outcome and its increasing incidence in the population. Current treatments are focused on the reperfusion of the occluded artery with IV thrombolysis and endovascular therapy (EVT). However, despite 90% of successful

Neutrophils are known as the first barrier to bacterial challenge in acute inflammation, however characterizing their involvement in chronic inflammation and related diseases is an emerging research field. As they are characterized by an extremely short lifetime, homeostatic neutrophil biogenesis le

The role of Platelet Concentrate (PCs) in such adverse reactions (ARs) and low transfusion yield could be related to the inflammatory function of platelets. Their contribution to the haemostatic response, platelets are innate immunity cells that lead to pro-inflammatory events. This study aims t

Epilepsy is a common neurological disease, with 1% incidence and, despite multiple available anti-epileptic molecules, ~30% of the patients are drug-resistant. Brain surgery is an effective therapy for an important number of these patients. Intracerebral Stereo EEG (SEEG) is the method of choice to

Quantitative magnetic resonance imaging (MRI) allows precise characterization of pathophysiological processes in healthy and damaged tissues at the individual level and is a technique of choice in the field of precision medicine. Despite this strong potential and the numerous quantitative biomarkers

Pneumonia is a world-wide major cause of morbidity and mortality. To date, the most common treatments of pneumonia are antibiotics or antiviral drugs. However, these pathogens-targeted therapies do not result in favorable outcomes for 10 to 30% of patients, indicating that additional host-targeted a

Myeloproliferative disorders (MPD) are acquired haematological diseases often due to the acquisition of the activating JAK2V617F mutation in a hematopoietic stem cell, that leads to increased production of platelets, red cells and leukocytes. Thrombosis reveals MPD in about 30% of patients and is th

Cerebral cavernous malformations (CCMs) are common inherited and sporadic vascular malformations of the central nervous system. While CCMs have been linked to mutations in one of three genetic loci, CCM1, CCM2 and CCM3 in 80% of inherited cases, the genetics of sporadic CCMs were poorly understood u

Given the paucity of effective treatments for idiopathic pulmonary fibrosis (IPF), efforts should be made to test and to better characterize new anti-fibrotic drug candidates. The recent development of RNA-targeted therapies using chemically modified oligonucleotide (ASOs) therapeutics show promisin

X-linked adrenoleukodystrophy (X-ALD) shows a phenotypic variability, ranging from the devastating inflammatory childhood cerebral ALD to a progressive spastic paraplegia in adulthood. Lipid compounds, which are abnormal in X-ALD, play a critical role in the differentiation states of macrophages, ce

Huntington disease (HD) is a devastating adult-onset dominantly inherited neurological disorder. Unmet medical needs: There is currently no treatment to delay or prevent appearance of the symptoms. Patients are heterozygous for the mutation, an abnormal CAG expansion in the HTT gene, and thus produc

Molecular defects in any step megakaryopoiesis, a process that achieves the platelet production, can lead to thrombocytopenia that could be inherited or acquired. Inherited macrothrombocytopenia (macroIT) represent one of three main groups of ITs and are mainly characterized by mutations in genes in

Articular cartilage damage of the knee often occurs in young active people. It can result from trauma, repetitive injuries or inflammatory conditions. Patients often opt for surgery which aims to fill the cartilage lesion to not only restore joint function, but also to reduce the inconvenience of th

A novel connective tissue disorder combining vascular and skeletal abnormalities has been recently associated to bi-allelic loss of function variants in IPO8. IPO8 codes for importin 8, a member of the ?-karyopherin family involved in cytoplasm-to-nucleus shuttling of a broad range of cargos. We hav

Glycogen storage disease type III (GSDIII) is a rare genetic disorder due to mutations in AGL gene encoding the glycogen debranching enzyme (GDE). This enzyme plays a key role for the degradation of glycogen into glucose in the liver and muscles. Mutations in AGL gene lead to toxic glycogen accumula

Genome editing (GE) technologies based on CRISPR/Cas systems allow targeted genomic modification and have emerged as powerful alternatives to conventional gene addition for various human diseases, with a series of clinical trials in progress. However, some challenges remain to be addressed to obtain

With an estimated 1.5 million deaths in 2020 according to the WHO Report 2021, Tuberculosis (TB) remains a major public health issue. On average, 5-10% of individuals exposed to Mycobacterium tuberculosis (Mtb) develop active TB disease, but the emergence of antibiotic resistance has made TB increas

AI-DIAL aims to decrease the rate of unnecessary adrenal surgery by more accurate diagnostics and improved surgical planning. We will build and exploit an unrivaled retrospective database of > 1500 adrenal surgery patients. Artificial intelligence (AI) use will enable a more detailed image feature a

Impulse control disorders (ICD) are the main neuropsychiatric side effect induced by pharmacological treatments in Parkinson's disease. They are characterized by behavioral addictions which affect around a quarter of patients and represent a major clinical and public health problem due to the lack o

Since January 2019, Dr. Emeric Limagne has focused his research on chemo-immunotherapy resistance in immunologically "cold" tumors. The present project is a continuation of work done in lung cancer and recently published in Cancer Cell. This work shows that in KRAS mutated cancers, the combination o

The cblC type of rare disease of vitamin B12 metabolism due to mutations in the MMACHC gene is a severe and sometimes fatal disease with metabolic decompensation, megaloblastic anemia, retinopathy, neurological disorders. We have discovered a new type of cblC called epi-cblC produced by an epimutati

Corona virus disease 2019 (COVID19) is induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and caused over 5 million deaths world-wide in less than two years. Despite intense researches it is not clear how long last the immune responses against SARS-CoV-2 following infection or v

Severe deficits in social interactions are one of the hallmarks of schizophrenia. Prominent hypotheses have suggested that social deficits are primarily the result of impaired social skills or deficits in social cognition. The role of nonverbal communication, and in particular speech synchronization

Major depressive disorder (MDD) is a complex multifactorial disorder. More than half of the patients show no clinical improvement in response to first-line antidepressants (ADs). Understanding of these individual differences in ADs responses is a first step to personalized medicine. For that purpose

Tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK) form a clinical continuum associating muscle weakness with anomalies of the bones, skin, spleen, and platelets. TAM/STRMK arises from gain-of-function mutations in the Ca2+ sensor STIM1 and the Ca2+ channel ORAI1, inducing an over-acti

Thanks to the recent progresses in healthcare management, most patients survive after acute brain injury and the society must face several issues concerning the growing burden of disability and ethical questions related to withdrawal of life sustaining treatment in absence of certain prognostic mark

Preterm-birth brain injury (PBI) is a public health concern, with many surviving children developing cognitive and neuropsychiatric deficits implying a strong social and economic burden. The developmental period around birth is a time of active generation of oligodendrocytes, myelination, and axonal

In a previous ANR project, we showed that glibenclamide, a sulfonylurea which binds SUR1 and SUR2 receptors, even at non-hypoglycemic doses, protects the retina from neuronal destruction in models of hyperglycemia and excitotoxicity. We have shown that this effect is dependent on the SUR1 protein wh

Epigenetic modifications of histones such as acetylation can modify chromatin structure, modulating gene expression. This acetylation plays a key role in transcriptional regulation during embryonic development. The CBP and p300 proteins are transcriptional co-factors belonging to the KAT3 family of

Adoptive cellular immunotherapy has emerged as a fascinating approach to prevent and/or limit graft-versus-host disease (GVHD), a major source of morbidity and mortality following allogeneic transplantation. To date however, the most appropriate regulatory population to use remains elusive. Human mu

Neurodevelopmental disorders (NDDs) result from anomalies occurring during brain development. Prevalence of NDD is estimated to 1 to 2% of the population worldwide. NDD have an important genetic contribution characterized by an extreme heterogeneity, with more than a thousand of genes identified in

Enterobacter is a known pathogen of fulminant sepsis in neonates as well as in immunosuppressed patients. We have recently shown that a structural modification of lipid A in Enterobacter endotoxins, specifically the presence of 2-hydroxymyristate (2-HM), is associated with excess neonatal mortality

To regulate inflammatory response, the host produces two main families of inflammatory mediators that are the cytokines and the oxylipins. These mediators act in concert to initiate the cardinal signs of inflammation and orchestrate its resolution. However, in clinics or in research, oxylipins are l

Osler-Weber-Rendu disease is a rare vascular dysangiogenic disease characterized by visceral arteriovenous malformations (AVM) in multiple localizations. Medical imaging plays a prominent role in the detection of AVMs and their complications. In the last decade, anti-angiogenic agents such as bevaci

This translational project aims to identify the developmental mechanisms and biomarkers of cognitive impairment and epilepsy associated with mutations of the gene syntaxin-binding-protein 1 (STXBP1). STXBP1 haploinsufficiency is one of the prevalent causes of developmental neurological disorders, in

Major depressive disorder (MDD) is the leading cause of incapacity worldwide. The varying degrees of efficacy of antidepressant drugs justifies further investigation of the mechanism of action of antidepressants. Accumulating evidence suggests that synaptic plasticity is involved in the pathological

Pertussis resurgence is associated strain vaccine-escape evolution driven by acellular vaccines, with a possible impact on vaccine effectiveness and clinical presentation in children. The mechanisms responsible for this clinical variability and the development of its most severe form, fulminant pert

This project aims to determine the potential therapeutic benefit of the iron- binding proteins, transferrin and lactoferrin, in the prevention of early stage of retinopathy of prematurity (ROP). ROP, one of the leading causes of blindness in children, is secondary to excessive oxygen delivery and ox

Biliary atresia (BA) is a severe uncurable paediatric liver disease manifested as a fibroinflammatory destruction of the biliary ducts. There are no drugs for BA making it the most common cause of liver transplantation in children. Despite its serious health impact and high socioeconomic cost, there

Infections are a major health issue worldwide and antibiotic resistance is a serious public health threat. Pseudomonas aeruginosa is a critical priority 1 for research and development of novel therapies, considering high prevalence, high mortality rates, and limited therapeutic options. It is partic

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease caused by the loss of motoneurons in the brain and spinal cord. Each year, ALS is responsible for three to five deaths per 100 000 people. ALS usually begins between the age of 50 and 70 with muscle weakness progressing ra

An age-related decline in lower limb neuromuscular function, including alterations in both neural and muscular factors involved in muscle force production is known to be one of the most important factors involved in the loss of physical abilities, balance impairment and risk of falling in elderly pe

The control of onchocerciasis, a disease due to a parasitic worm (a filaria) found in 31 African countries, relies on the mass treatment (without prior individual diagnosis) of the population living in meso-hyperendemic areas. Loiasis (Loa loa filariasis) is not subject to specific control programs

Symptomatic sinus node dysfunction (SND) is the most common bradyarrhythmia and the leading cause for over 500,000 electric pacemaker devices implanted yearly in Europe and U.S. In recent years, an increasing number of mutations affecting ion channels involved in sino?atrial automaticity, including

CADASIL is an autosomal dominant small vessel disease of the brain leading to severe disability and cognitive decline without specific treatment. The disease is caused by highly stereotyped mutations in the NOTCH3 receptor leading to the abnormal accumulation of the extracellular domain of NOTCH3 (N

HNF1B is a transcription factor whose mutations represent the most common genetic cause for “Congenital Abnormalities of the Kidney and the Urogenital Tract” (CAKUT). In addition, mutations in HNF1B may also be found in adults with Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD), a rar

Sudden cardiac death (SCD) is a major cause of adult mortality, accounting for about 350 000 deaths in Europe annually. SCDs in patients without structural heart disease are caused by ventricular arrhythmias generated from areas with abnormal electrical properties (‘substrate’) present within the he

Anaplastic thyroid carcinoma (ATC) is a rare and very aggressive disease. Even with multimodality treatment, the prognosis remains very poor with overall survival between 6 and 12 months. Following seminal work from our team, we hypothesize that ATC aggressiveness and resistance to treatments are

Background: The combination of immunotherapy (atezolizumab) and anti-angiogenic antibody (bevacizumab) is the standard of care in first line for advanced hepatocellular carcinoma (HCC) whereas tyrosine kinase inhibitors such as sorafenib/lenvatinib are used in second line. However, only a subset of