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PhantomWalk will investigate whether somatosensory feedback of the lost lower limb after amputation can be restored by natural phantom sensations rather than by artificial substitution technologies. Our recent results, obtained through semi-structured questionnaires with 126 lower limb amputees, sho

Major depressive disorders (MDD) are severe disorders with heterogeneous clinical presentations that affect up to 20% of the general population. Response rate to antidepressant drugs is only 40 to 50%, leading to the use of drug combinations and development of alternative therapeutics such as light

Sepsis is defined as life-threatening organ dysfunction caused by a deregulated immune host response to infection. This syndrome involves a pro-inflammatory, anti-inflammatory state as well as an immunoparalysis at the origin of an increased susceptibility to secondary infections. Sepsis is estimate

Some severe forms of obsessive-compulsive disorder (OCD) may benefit from deep brain stimulation (DBS) of the subthalamic nucleus. So far, the number of OCD patients treated with this innovative therapy remains limited, and although strict inclusion criteria have been defined based primarily on lesi

The development of High-Resolution Computed Tomography (HRCT)-scan has been a major revolution in pulmonology and particularly made a breakthrough in interstitial lung diseases (ILDs) classification. ILDs compose a large and heterogeneous group of disorders characterised by a large spectrum of diffu

Bariatric surgery (BS) is the most effective treatment to achieve durable weight loss, despite a large variability among individuals. BS has been associated with major gut brain axis modifications impacting eating behavior, food preferences and sensory perceptions. The gut microbiota (GM) is a key p

Cobalamin (Cbl, or vitamin B12) is the cofactor for methionine synthase (MS encoded by MTR) and methylmalonyl-CoA mutase (MUT encoded by MMUT), whose genetic defects lead to increased homocysteine (Hcy) and methylmalonic acid (MMA), respectively. Inherited errors of Cbl metabolism (IECM) are produce

Viral pneumonia, including SARS-CoV-2 and influenza A virus (IAV), can culminate in acute respiratory distress syndrome (ARDS), a severe form of respiratory failure with high mortality. Uncontrolled local inflammatory response and impaired tissue repair are hallmarks of ARDS. However, lack of in-dep

Mitochondrial diseases result from deficiencies of oxidative phosphorylation due to mutations of nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). They are challenging genetic disorders owing to marked clinical variations seen in patients and the variety of organs that can be affected. Strikingly, de

Primary aldosteronism (PA) is the most frequent cause and possibly curable form of secondary arterial hypertension. PA is characterized by an aldosterone excess which is usually caused by either a unilateral adrenocortical aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH). B

Overweight, obesity, aging and menopause are all independent risk factors in the development of type 2 diabetes mellitus (T2DM). Older women with T2DM are at especially high risk for sarcopenia, i.e. loss of skeletal muscle mass and force, and cardiovascular diseases. The first line of T2DM treatmen

Cerebral folate deficiency (CFD), defined by a low folate cerebrospinal fluid (CSF) concentration, can be linked to genetic defects of folate metabolism or be secondary to various diseases without clear causal link, and be associated to potentially very disabling cognitive and motor symptoms. We ide

Amyotrophic lateral sclerosis (ALS) is a fatal age-associated neurodegenerative disease, which affects predominantly motor neurons in the cerebral cortex and the spinal cord. Overall, a positive family history for ALS is documented in approximately 5-10% of all ALS patients. The monogenic causes for

In Parkinson's disease (PD), akinesia and levodopa-induced dyskinesias (LIDs) are accompanied by synchronous and pathological neuronal oscillations in the cortico-subcortical network encompassing the basal ganglia and the thalamus (CGBT) with frequencies ranging from theta to gamma band. Deep brain

Early-life stress, such as childhood maltreatment or neglect, is a major risk factor for the later development of psychiatric disorders, particularly depression. These adverse experiences alter the maturation of neural circuits involved in emotion regulation and motivation. In parallel, depression i

Our Franco-German consortium aims at: - Deciphering the diversity and spatial distribution of ILC in joint tissues at different stages of OA and the correlation with the clinical features of the patients. - Investigating the contribution of ILC subsets to the pathophysiology of OA and evaluating the

Kidney failure affects between 1.7 and 2.5 million people in France. After transplantation, pharmacological immunosuppression (IS) is mandatory for the prevention of acute rejection, but induces serious adverse effects and is not effective in preventing chronic rejection. The minimization of IS and

Acute Brain Infarction complicating large vessel occlusion (LVO-AIS) are one of the first causes of neurological dependency and death in Europe. Their incidence is expected to increase by 20% in the next 10 years. Endovascular recanalisation (EVT) has revolutionized their management. It was initiall

Rejection remains the leading cause of failure following lung transplantation, directly impacting patient survival, quality of life, and the economic burden of care. Despite international guidelines and a standardized histological grading system (ISHLT), current diagnostics still rely heavily on his

The management of the acute ischemic stroke (AIS) remains a major challenge for modern medicine. The main goal of AIS treatment is to recanalize the occluded artery by removing the thrombus causing the ischemia as quickly as possible. There are two treatment options: intravenous thrombolysis (IVT) a

Over the last past years, the key roles of embryonic molecules/pathways in tumorigenesis have emerged and candidate drugs targeting these molecules/pathways have been developed. This has led to the clinical assessment developmental drugs/biologics and sometimes to clinical benefit for patients as ta

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a curative therapy for hematologic malignancies through the graft-versus-tumor (GVT) effect. However, relapse remains the leading cause of post-transplant mortality. Two main mechanisms contribute to relapse: tumor-intrinsic immune esc

Several studies have suggested that abnormal functioning of the blood-cerebrospinal fluid barrier and the lymphatic system may be involved in the pathophysiology of Parkinson's disease (PD) by contributing to abnormally folded alpha-synuclein deposition. In this project, we will determine (WP1) usin

Depression (MDD) resistant to antidepressant (AD) drugs has profound individual and societal impact. We have recently identified a novel AD target the transcription factor ELK1. Because ELK1 operates inside the cell rather than the synapse, where “classical” ADs act, this discovery could pave the ro

Obesity and overweight represent important public health concerns given their growing prevalence worldwide. These conditions are often associated with neuropsychiatric comorbidities. Major depressive disorder (MDD) is the most frequent, severe and disabling of those disorders, affecting about 30% of

Chronic Nasal Obstruction (CNO) is not measurable in clinical practice and represents an important lack for the clinician. In addition, the components of the NO are poorly known. Simulating the passage of air in the nose from the computer processing of the patient's scanner is a technology inaccessi

One-to three percent of uncomplicated malaria cases progress to the severe stage of the disease, including severe malaria anemia (SMA) and cerebral malaria (CM). Even when treated, cerebral malaria is fatal in 15-20% of CM cases. The factors determining the progression of the malaria pathogenesis ar

Stroke is caused by a sudden decrease of cerebral blood flow following the blockage of a brain artery. Today, the aim of the medical management is to limit brain damages by inducing the recanalization of the occluded artery. To date, thrombolysis by tissue type plasminogen activator (tPA) is the onl

Current available treatments for alcohol use disorder (AUD) show modest effectiveness, with a 50% rate of relapse during the first month following alcohol cessation. Psychedelic therapies hold good promises for AUD, but their effectiveness has not yet been attested in only few studies and the involv

Sanfilippo B syndrome (SFB) is a rare recessive genetic disease (approx 1/100 000 life births) due to the deficiency of a lysosomal enzyme that leads to a neuro-developmental alteration appearing early in life, before two years. Subsequent clinical expression of the neurodegenerative process leads t

Rhabdomyolysis (RM) is a vital emergency disorder with no specific treatment, characterized by the acute breakdown of skeletal myofibres in response to a triggering factor, e.g. fasting. Our team has been involved in the identification/description of multiple genes associated with RM including LPIN1

In the recent years, it has been shown that musculoskeletal failure and brain cognitive deficits are symptoms that are often intertwined and occur at the same time during aging, suggesting alterations of common regulatory mechanisms and molecular pathways. This is particularly true for the Fibroblas

Mammal’s hearing and balance functions rely on highly specialized sensory organs in the inner ear, the cochlea and the vestibule, the hearing and the balance organs, respectively. Deafness and balance defects are the most prevalent inherited sensory disorders in humans. Roughly 1 in 700 newborns a

In rare diseases affecting the head and neck area, dental developmental anomalies are often key diagnostic features orienting clinical diagnosis. These anomalies (tooth number: hypo/oligodontia (HO) and supernumerary teeth, tooth shape, size, structure of hard tissues (dentine, enamel, cement, alveo

Improving early recanalization and preventing neurovascular damage at the acute phase of ischemic stroke are the main objectives of current stroke research. In contrast, much less attention is being paid to the possibility of reversing and repairing post-stroke neurological damage. Previous studies,

Breast cancer is the most prevalent cancer in the world. Female breast tumours alone account for approximatively 11.7% of new cancer cases each year, with more than two million women diagnosed in 2020, which highlights this disease as a major public health concern. At the molecular level, this malig

Hereditary haemorrhagic telangiectasia (HHT) is a rare disease characterized by epistaxis, mucocutaneous telangiectasia and arteriovenous malformations affecting multiple organs. HHT associates with severe complications such as clotting, bleeding, hypoxia and anemia that can be fatal in 10% of cases

Osteoarthritis (OA) affects around 40 million people in Europe. OA causes a heavy socioeconomic burden. There is currently no cure for OA. Also, the development of therapies that can prevent joint damage associated with OA is thus urgently needed. OA is characterized by loss of joint cartilage, pat

Primary sjögren's syndrome (pSS) is a systemic autoimmune disease (AD) characterized by lymphocytic infiltration of the exocrine glands that carries the highest risk of lymphoma among ADs. Both T and B cells play major roles in pSS and ADs’ pathophysiology. While autoantibodies are often used for AD

Obesity is a complex disease, altering quality of life and life expectancy, for which innovative therapeutics approaches are urgently needed. Our team pioneered the description of excess deposition of extracellular matrix (ECM) resembling fibrosis in WAT depots of patients with obesity. We then cont

The pathophysiology of Crohn’s disease (CD) is complex and not fully understood. While CD can affect the entire gastrointestinal tract, it primarily affects the terminal ileum. The underlying mechanistic reasons for this preferential location are unknown. Patients with isolated ileal CD have higher

Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by a selective loss of motor neurons (MN) due to a deficiency of the SMN protein encoded by SMN1 gene. Recently approved therapeutic approaches, namely AAV-mediated replacement of the SMN1 gene (Onasemnogene abeparvovec) or modul

Inclusion body myositis (IBM) differs from other autoimmune myositis by its poor response to immunosuppressant therapies, and degenerative muscular features leading to marked disability. IBM is characterized by a strong IFN-gamma (IFN?) signature in muscle tissue, which is related to the CD8+ T-cell

MYPN-CM is an ultra-rare form of nemaline and cap myopathy caused by the loss of the sarcomeric protein myopalladin, leading to progressive muscle weakness and a significant impact on quality of life. No curative treatment exists, and the development of a targeted therapy is hindered by the rarity o

Mastocytosis is a heterogeneous disease characterized by an accumulation of mast cells (MCs) in the skin or various organs. The systemic form includes indolent and aggressive forms such as mast cell leukemia. Somatic mutations activating the KIT receptor tyrosine kinase (TK) are found in 90% of case

PVNS is associated with abnormal fibroblastic cells, often involving a specific chromosomal translocation resulting in the overexpression of colony-stimulating factor 1 (CSF1 or M-CSF), recruitment of CSF1 receptor (CSF1R) macrophages and fusion in giant cells. PVNS is the articular form of tenosy

Primary central nervous system lymphoma (PCNSL), a rare subtype of extranodal non-Hodgkin’s lymphoma (NHL), is defined as a diffuse large B-cell lymphoma (DLBCL) arising exclusively within the brain, spinal cord, leptomeninges, or eye according to the new WHO Classification of Tumors of the Central

Focal cortical Dysplasia (FCD) is one of the major causes of focal onset seizures refractory to antiepileptic drugs (AEDs). Only one-third of these patients are eligible for epilepsy surgery (i.e. the removal of the epileptogenic area), which offers the chance of seizure remission for 30%-40% of pat

The immune system plays a central role in the response to anticancer treatment. T CD8 lymphocytes and Natural Killer (NK) cells can, using their cytotoxic ability, directly kill tumor cells but numerous immunosuppressive mechanisms aim at limiting those antitumor responses. Immune checkpoint inhibit

IgA responses, as the most ambivalent facets of immunity, are also strongly involved into immunopathology. At both systemic and mucosal sites, IgA responses mix inflammation with implication in tolerance. Their mutual dependence with the microbiota illustrates a crucial [gut – immunity axis] which,

Actin is a cellular compound that forms fibers that support the skeleton of cells (cytoskeleton). Actin remodeling is a biological process that allows the cell to move and deform to migrate through body tissues. This process is finely regulated by intracellular signals and in particular by the DOCK

Cerebral Small Vessel Diseases (SVDs) are among the most prevalent disorders that impact brain health at the population level and contribute to increased disability and mortality with aging. A major hurdle to the development of disease-modifying drugs in SVDs is that, today, these conditions are onl

Obesity is associated with increased severity of infectious diseases. There is an urgent need to provide adapted lifestyle recommendation to reduce that risk which could be due to low grade inflammation and increased immune checkpoint (ICP) overexpression such as the PD-1/PDL1 pathway that leads to

Spinal cord (SC) Magnetic Resonance Imaging (MRI) has greatly improved over the last decade, however it still remains underexplored : assessing subtle details such as small lesions or the central vein sign, which may change the diagnosis of Multiple Sclerosis (MS) for instance, is not yet possible;

Rejection currently represents the major cause of allograft failure worldwide, with immediate consequences for the patients in terms of mortality, morbidity and cost for the society. Improvement of diagnostics and prognostics are required for better patient stratification, personalized treatment, an

We have recently shown that glucose-dependent insulinotropic polypeptide (GIP)-dependent primary bilateral macronodular adrenal hyperplasia (PBMAH) with Cushing’s syndrome, is a genetic disease caused by germline inactivating mutations in lysine demethylase 1A (KDM1A or LSD1) with loss of heterozygo

In the retina, the metabolic activity of photoreceptors relies on choroidal blood flow, tightly regulated by nerves from the autonomous nervous system (ANS). Retinal imaging has recognized “pachychoroid”, defined as thick choroid, dilation of choroidal vessels and attenuation of the choriocapillaris

As emphasised by the SARS-CoV-2 pandemic, understanding the pathogenesis of inflammatory lung disease is of high relevance to human health, with persistent pulmonary inflammation leading to fibrosis and end-stage respiratory failure. The potential of type I interferon (IFN) to mediate lung inflammat

Inherited retinal diseases (IRDs) are a major cause of retinal degeneration leading to progressive blindness with limited therapeutic options. The last decades have seen promising therapeutic development urging for a better characterization and understanding of IRDs. The genetics of IRDs is heteroge

We will study the role of a frequent human coding polymorphism in a nicotinic acetyl-choline receptor (nAChR) gene, developing and using pre-clinical models and implementing a novel pharmacological approach to target specifically the mutated nAChRs. Our project is based on robust Genome-wide Associa

On one hand, vaccines against infectious diseases have saved countless lives and improved the overall health of the world’s population, first by using attenuated viruses or recombinant proteins, and now by using mRNA translated into antigens. While vaccines against pathogens are known to be effectiv

Endometriosis is a chronic estrogen-dependent inflammatory gynecological disease that affects nearly 10% of women of childbearing age and up to 40% of infertile women, with diagnosis wandering of 6 to 10 years. Endometriosis is defined as the presence of endometrial tissue outside the uterus. Women

Adapted Physical activity (APA) is a new putative therapeutic tool in anorexia nervosa (AN) but randomized clinical trial are still lacking, such as mechanistic studies. In activity-based anorexia mice (ABA), we previously reported that maintained physical activity during refeeding is associated wit

Nosocomial central nervous system (CNS) infections in intensive care unit (ICU) patients remain therapeutically challenging because of drug- and disease-related factors that contribute to suboptimal antibiotic concentrations in CNS. Moreover, antibiotic dosing regimens recommendations for meningitis

With the population aging, the number of calcific aortic valve stenosis, the most frequent valvular heart disease, is expected to double in the next 20 years. So far, no pharmacological treatment is available, the only option is to perform an aortic valve replacement (AVR). A shift toward the use of

Multiple endocrine neoplasia type 1 (MEN1) is a rare disease caused by mutations in the tumor suppressive gene MEN1. The 3 cardinal lesions are primary hyperparathyroidism, pituitary tumors, and neuroendocrine duodeno-pancreatic tumors. 27 to 70% of MEN1 patients die due to the disease. Despite a ve

Cystic fibrosis (CF) patients often died from the consequences of recurrent chronic respiratory infections mostly due to Pseudomonas aeruginosa. These infections are not controlled due to frequent antibiotic-resistance, a tolerance to antimicrobials due to bacteria forming biofilms. Since new antimi

Spontaneous coronary artery dissection (SCAD) is an acute cardiac event, mostly affecting young, otherwise healthy, women, which can recur with potential deathly consequences. Up to 50% of SCAD patient present lesions of fibromuscular dysplasia (FMD) in other arteries, supporting a clinical link bet

Sudden cardiac death (SCD), instigated by cardiac arrhythmias forms a significant healthcare burden in Europe with over 350,000 fatalities reported annually. Implantable cardioverter defibrillators (ICDs), are the mainstay treatment for lethal ventricular tachyarrhythmias (VT/VF), however, they suff

Centronuclear myopathies (CNM) are rare congenital myopathies characterized by abnormal central position of nuclei in the muscle fibers in absence of muscle regeneration. The three main forms include the X-linked recessive CNM due to Myotubularin (MTM1) mutations, and the autosomal forms due to domi

hile the protective role of cerebrospinal fluid (CSF) during traumatic impact has been emphasized and is now accepted, little is known about the role it plays during the subacute, intermediate and chronic phases of wound. The goal of BioMechCSF is to advance fundamental understanding of the biomecha