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Clinical and experimental studies have reported biological rhythms impairments (fast/feeding cycles) in obese subjects but also memory alterations. This is particularly worrisome for adolescents as the brain is still maturing. Our hypothesis is that deregulation of the circadian clock, induced by ob

ICSI is becoming the most common ART technique, used in 70% of attempts. Questions about its effectiveness and safety have emerged. The majority of children conceived by ICSI are healthy but are at risk of neonatal complications. But the origin of this risk, related to parental characteristics or th

The number of old people is rising worldwide and cardiovascular diseases are the largest contributor to morbidity and mortality in this population. Changes in diet and lifestyle contribute to the high cardiovascular morbidity and mortality in old individuals, but many biological processes that are a

Macrophages (MF) populate all our tissues, from the embryonic stage to adulthood. In the testis, peritubular MF cover the surface of the seminiferous tubules while interstitial MF are interspersed between the testosterone-producing Leydig cells. The functions of these two types of MF are currently u

The cAMP-dependent protein kinase (PKA) is the canonical effector of the ß-adrenergic (ß-AR)/cAMP cascade and a major physiological regulator of cardiac function. In the adult heart, PKA mediates the cardiotonic effects of acute ß-AR stimulation, but persistent PKA activation has been linked to mala

Cells release information (RNA / Protein / Lipids) into lipid nanovesicles called extracellular vesicles (EVs). We have shown that EVs released by skeletal muscle during the development of insulin resistance had virus-like properties and transferred deleterious information between insulin-sensitive

Retinopathy of prematurity (ROP) is the leading cause of blindness in children. This disease is characterized by inflammatory processes and abnormalities in vascular development of the retina. Preliminary results from our laboratories and published data show that specific lipids, such as plasmalogen

The liver orchestrates metabolic response to fasting through potent transcriptional regulations. Peroxisome Proliferator-Activated Receptor alpha (PPARa) and the Glucocorticoid Receptor (GR) are pivotal transcription factors in these adaptive processes. They control a network of genes, including Ret

Pancreatic islets are central to nutrient homeostasis and diabetes. They contain 4 cell types (alpha/beta/gamma/delta), which alter their electric activity that tightly regulates hormone secretion in a distinct biphasic and pulsatile manner for up to 3 hours after a meal to restore homeostasis. The

The overarching goal of the DISNEy proposal (Dynamic Interplays of the Synovial Niche Ecosystem) is to gain new insights into the mechanisms involved in the homeostatic regulation of the synovial tissue niche by focusing on macrophages and their relationships with the microenvironment of the synovia

Von Willebrand disease (VWD) is an inherited bleeding disorder resulting from quantitative or qualitative deficiencies in von Willebrand factor (VWF), a plasma glycoprotein, crucial to platelet thrombus formation during primary hemostasis. Despite existing treatment options, quality of life is signi

Age-related hearing loss (ARHL) is the most common sensory disease ranking among the top five in the global burden of disease study with considerable negative impact for the persons affected and considerable costs for the society. If not detected and treated early on (e?g. with hearing aids), it inc

Complement proteins have been considered for long to act only within this plasma-born enzymatic cascade, evolved to fight infections and to clean debris. Nevertheless, recent research, including from the DYSALARM partners, demonstrated that the complement proteins crosstalk with other systems and ca

Spinal cord injury (SCI) results in multi-organ impairment leading to increased risk of morbidity, mortality and disability. Symptoms resulting from spinal cord injury include pelvic (urological and digestive) disorders, which also have a major impact on the quality of life of SCI persons. To date,

Muscle dysfunction is implicated in a plethora of human diseases and in sarcopenia, i.e. muscle atrophy with age that constitutes the leading cause of loss of ambulation and independence. This project aims at identifying important pathways for muscle intracellular organization, under physiological a

Sickle cell disease (SCD) is a genetic recessive inherited disorder caused by a Glu-to-Val substitution in the ß globin protein resulting in abnormal hemoglobin (HbS) that polymerizes under hypoxia driving red cell sickling and reduced half-life. SCD is a severe multisystem disease characterized by

GREB1L is a causative gene of a spectrum of human congenital defects, including renal agenesis. Yet the encoded protein is poorly characterised. Since the pathophysiology of congenital defects cannot be assessed in patients, it is essential to trace back origins in the embryo and identify the cellul

Gonadal sex fate in mammals is determined during embryonic development and must be actively maintained through adulthood. Therefore, gonadal sex-specific transcription factors are required to prevent transdifferentiation of adult gonadal somatic cells into the alternate sex fate. In mouse ovary, oes

The intestinal epithelium is a constantly renewing tissue that quickly adapts to its environment. The microbiota and immune cells, in contact with intestinal epithelial cells, can impact their functions and thus modulate nutrient absorption, hormone secretion and barrier function of the gastrointest

Pressure overload stretches the myocardium leading to functional and eventually structural adaptations if the mechanical stress persists. Repetitive ventricular stretch can result in physiological remodeling of the heart as is observed in response to exercise training. However, when this stress is c

Type 2 diabetes (T2D) is a life-threatening chronic disease associated with aging and a poor lifestyle. T2D is characterized by peripheral insulin resistance and impaired insulin secretion. The central aim of MYODIAB is to elucidate the interplay between skeletal muscle, adipose tissue and pancreati

The lysosome is a signaling controller hub implicated in virtually every aspect of cellular physiology. Among myriad of assigned processes, a special attention was given to the master growth signaling pathway: mTORC1. Under stimulation, this multimeric complex is assembled and activated on the lysos

The interstitial fibrosis is a major health problem because it causes dysfunction of many organs and is responsible for a high degree of morbidity and mortality due to organ injury. The frequency of pathologies with fibrosis increases progressively due to aging of the population and increase in ris

Treatment options for ulcerative colitis improved significantly in the last years, but many patients are either non-responsive or become resistant during drug regimen underpinning the urgent need to develop novel biomarker-guided therapeutic approaches. Primary cilia (PC) are an important signaling

The visceral adipose tissue (VAT) is a highly dynamic organ that responds to nutrient and environmental stress to regulate host metabolism. In response to excess caloric intake, pathological VAT remodeling leads to adipocyte hypertrophy, a shift toward pro-inflammatory type I immunity and ECM accumu

Rosacea is a chronic and multi-factorial skin disease with a prevalence among adults in some countries as high as 20%. Unpleasant sensations such as stinging and burning, pain, and significant skin dryness are associated with the pathology. Moreover, rosacea is localized primarily on the face and th

The intestinal tract is home to a densely populated microbial community, or microbiota. A growing body of evidence suggests that this commensal relationship strongly defines the health state of humans. Within this community, the richness and diversity of bacteria are shaped by the intestinal physiol

Background: Due to the obesity epidemic, it is urgent to study diet-induced functional changes of neuronal circuits integrating the diverse components of feeding behavior (food hedonic and incentive salience, actual food intake) with the metabolic status of the organism, as those circuits may be rel

Gastrointestinal (GI) motility, i.e. the coordinated muscular contraction of the gut, is essential to the health and well-being of individuals of all ages. These movements originate from layers of smooth muscles that rhythmically contract through the coordination of the enteric nervous system (ENS)

Metabolic Associated Fatty Liver Disease (MAFLD) is a major public health concern. Alarmingly, steatosis (NAFL) progresses pejoratively to Non-Alcoholic Steatohepatitis (NASH), which is considered as a growing worldwide epidemic threat, due to the absence of treatment. METALECT data strongly suggest

A high prevalence of invasive Escherichia coli strains, designated as adherent-invasive E. coli (AIEC), has been frequently observed in the ileal mucosa of Crohn’s disease patients. Preventing the colonization of ileal mucosa by AIEC could be a strategy to limit recurrence of CD. Based on solid prel

State of art The physicochemical properties of drugs can lead to a therapeutic failure. Physicochemical properties can predictably influence intracellular distribution of a drug, an important consideration for its efficacy. In particular, drugs with LogP> 2 and pKa> 6 can be trapped in acidic intra

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of extracellular matrix (ECM) by myofibroblasts, leading to impaired gas exchange and ultimately death due to lack of effective treatments. Fibrosis is a feature of most chronic inflammatory diseases. We recently identified

Enteroendocrine cells (EECs) are rare cells found along the intestinal mucosa and represent the largest endocrine system in the human body. EECs sense nutrients and dietary metabolites generated by the gut microbiota in the intestinal lumen and, in response, secrete a variety of hormones that act lo

Islets of Langerhans are micro-organs scattered throughout the pancreas and made up of beta, alpha, delta, PP and epsilon cells, which secrete insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. Our knowledge of beta cells has exploded thanks to the many models that have allowed the

The objective of the VIRCHILLD project is to identify age-related modifications of the bronchial epithelium physiology able to explain differences in the response to respiratory viruses’ infection. Several epidemiological and cell-based data have demonstrated that respiratory virus infections differ

Resident tissue macrophages (RTM) are essential cellular components of adult tissues regulating homeostasis beyond their classical immune surveillance functions. The heart is an archetypal example of adult tissue with RTM. Cardiac RTM represent around 6% to 8% of the non-cardiomyocyte population in

Metabolic status is one of the major determinants of healthy aging and life expectancy. The brain controls metabolism through the activity of neuronal networks that integrate hormonal signals from peripheral organs and induce behavioural and metabolic responses. We have shown that reduction of Dlx5/

Chronological age is the most important individual risk factor for the development of acute and chronic conditions such as cardiovascular diseases. However, the effects of aging on innate immune responses in cardiac inflammation and healing are poorly understood. Macrophages are professional phagocy

In mammals, sperm fertilization potential relies on efficient progression within the female genital tract to reach and fertilize the oocyte. This fundamental property is supported by the flagellum that provides the mechanical force for sperm propulsion, and is also conditioned by maturation processe

The ionic homeostasis of organelles in the secretory pathway is crucial to many fundamental cellular processes such as vesicular fusion events, protein secretion as well as the activity of many glycosylation enzymes. This project aims to understand the interplay between TMEM165 (involved in a human

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can present with a range of manifestations. SARS-CoV-2 infects type II pneumocytes by binding to membrane-bound angiotensin-converting enzyme 2 (ACE2). Rapidly after the outbreak, re

Obesity and type 2 diabetes (T2DM) are strongly associated pathologies and are considered by the World Health Organization as an epidemic worldwide issue. Current treatments for T2DM, targeting the peripheral action of insulin, do not always succeed in balancing patients' diabetes. It is therefore b

Renal diseases can be progressively complicated by Chronic kidney diseases (CKD), whatever the initial renal injury. CKD represent a worldwide health concern: about 10%-15% of the overall population is affected by CKD worldwide and this number is expected to increase. CKD has also dramatic consequen

Testicular tissue freezing (TTF) is proposed to preserve the fertility of prepubertal boys before highly gonadotoxic cancer treatment. In vitro spermatogenesis is one of the potential approaches that could be used to restore male fertility after recovery. Because of the scarcity of human prepubertal

Cardiovascular disease (CVD) and its clinical manifestations, such as myocardial infarction and stroke, are the leading cause of mortality worldwide. Elevated plasma cholesterol concentrations are directly implicated in the development of atherosclerosis, the underlying pathology of CVD. Our previou

Few genes are involved in thyroid dysgenesis (TD) causing congenital hypothyroidism (CH) that occurs in about 1:3000 newborns. Recently, we identified a novel gene, TUBB1, involved in CH due to TD. TUBB1 encodes for a ß-tubulin isotype – one of the basic building blocks of microtubules (MTs) and str

Aging is characterized by a progressive loss of physiological integrity, leading to age associated frailty. The hallmarks of aging include cellular senescence, telomere attrition and metabolic disorders. Remarkably, during aging the liver is one of the first organs displaying these particular traits

Caffeine is the most consumed psychoactive substance in the world, including during pregnancy and breastfeeding. It has an impact on public health which depends on the period of exposure. Our consortium has shown that perinatal exposure has detrimental effects on brain maturation, promoting seizures

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries, whose incidence is rapidly expanding worldwide. NAFLD is a frequent comorbidity of type 2 diabetes and obesity with its prevalence evaluated at ~30% in the general population and 80% among

Despite major progress in the treatment against atherosclerotic cardiovascular disease (ASCVD), new therapeutic alternatives are needed for patients at very high ASCVD risk and/or with side effects upon available therapies. Recently, the inhibition of the G protein-coupled receptor 146 (GPR146), a f

Myositis are autoimmune diseases characterized by inflammation of skeletal muscle causing weakness and increased mortality. Glucocorticoids (GC) improve the disease through currently unknown mechanisms (therapeutic effect) but expose to many adverse events including steroid-induced myopathy (iatroge

Actual strategies to treat type 2 diabetes (T2D) are based on improving either insulin action OR secretion. In the needed quest to find new therapeutics, it is interesting to note that there is no strategy that simultaneously improve insulin action AND secretion, partly due to our limited understand

Polymorphisms in autophagy-related genes, which lead to dysregulated autophagy, Western diet and an abnormal colonization of the ileal mucosa with adherent-invasive E. coli (AIEC) have been revealed as risk factors for Crohn’s disease (CD). This project aims at (i) investigating the effect of Wester

Our skin is much more than just a physical barrier. It is populated by many types of cells – structural, neural, and immune – that work together to detect external challenges (such as allergens or injuries) and respond appropriately. This complex system helps maintain the balance and health of the s

The adrenal glands are tiny organs perched on top of our kidneys, but they punch far above their weight. They release hormones that regulate blood pressure, salt balance, stress responses, metabolism, and inflammation. To do this, they rely on their two main parts: the medulla, which makes stress ho

Intracranial aneurysm is an asymptomatic cerebrovascular abnormality characterized by focal dilation of the vascular wall, affecting approximately 3% of the general population. Its rupture is unpredictable and leads to subarachnoid hemorrhage, which can cause neurological sequelae or lead to death i

It is known that adult myofibers diversity, and more particularly their fast subtypes is finely controlled by corresponding motoneuron (MN) diversity, yet the determinants of this MN diversity and how their specific properties may finely tune myofiber phenotypes remain to be characterized. The over

Control of energy homeostasis requires a permanent dialogue between the periphery and the brain. The median eminence (ME) is at the interface between the bloodstream and the hypothalamic arcuate nucleus (ARH), a key center controlling metabolism. Blood-borne molecules reach the ME parenchyma but can

The kidneys have a great capacity to retain salt (Na+, Cl-) and to excrete potassium (K+) and an alkaline load (HCO3-), which was, until recently, in perfect adequacy with our food intake. However, in recent decades, our diet has changed dramatically. Thus, in addition to very high fat and sugar int

Microglia are tissue-resident macrophages in the central nervous system where their role is to sense changes in the environment. Microglia are multifunctional cells that can interact with other cells in the CNS. Tissue-type plasminogen activator (tPA) is a zymogen expressed in the endothelial cells

The autonomic nervous system (ANS), that regulates involuntary body functions divides into the parasympathetic (PANS) and sympathetic nervous system (SANS). The output from the SANS is through sympathetic preganglionic neurons (SPNs) lying in the thoracolumbar part of the spinal cord (SC). Highly sp

We have performed an exome sequencing of a family of patients with an aggregation of very severe forms of ankylosing spondylitis. We identified a rare missense variant of the BbSp gene carried by all family members with a severe form of the disease. The corresponding amino acid is highly conserved a

Dravet Syndrome (DS) is a severe epileptic encephalopathy, which main cause is mutations of SCN1A and which associated with high risk of sudden death (SUDEP). Experimental and clinical data suggest that most SUDEP cases result from postictal brainstem dysfunction, including central respiratory arres

Elevated serum phosphate (Pi) is a life-threatening condition which promotes the development of vascular calcifications (VC) and is associated with increased mortality in patients with chronic kidney disease (CKD). High Pi load triggers calcification of the medial layer of the arterial wall resultin

The melanin-concentrating hormone (MCH) is a major hypothalamic peptide involved in energy homeostasis. MCH binds to its two receptors MCHR1 and MCHR2, which are expressed in the human brain. Strikingly, MCHR2 is absent in rodent genomes (rat, mouse). While mouse strains over-expressing or deleted f

Systemic inflammation develops with overeating and excessive calorie intake. This chronic nutrition-related inflammation has deleterious effects on the body, promoting the development of metabolic diseases such as obesity or type 2 diabetes. We have recently observed that an acute and brief inflamma

Fatty liver diseases among which alcoholic and non-alcoholic steatohepatitis [(N)ASH] have become a major health issue worldwide as they represent a major cause of liver failure and cancer. This is due to liver insult leading to fibrosis, a detrimental excess of extracellular matrix (ECM) deposition

The deleterious role of cellular senescence is well documented in cardiac and renal disorders and is linked with "inflammaging", i.e. release of pro-inflammatory cytokines and impairment in immune cell. DOX-EPISEN aims to better understand the pathophysiology of cellular senescence-related syste

Information on SARS-CoV-2 infection risks in pregnant women and their offspring has so far been limited to small case series. Our objective is to explore from a large clinical-biological cohort, the obstetric, fetal and neonatal repercussions of SARS-CoV-2 and understand its pathophysiological mecha

Based on encouraging pilot data, we hypothesized that a specific subtype of innate lymphoid cells, called NK cells, exerts toxic effects on cardiomyocytes after acute myocardial infarction, promoting the extension of the infarction, deleterious remodeling of the left ventricle and ultimately heart f

ETV6 is an ETS family transcription factor that controls the maintenance of hematopoietic stem and progenitor cells (HSPC) and thrombopoiesis that leads to the formation of blood platelets. Using exome sequencing, we were one of the top three groups in the world to identify pathogenic variations of

Proposal context: Obesity prevalence is tightly associated with cardiometabolic morbidity. Growing evidence supports that adipocyte dysfunction is central in the development of obesity-related metabolic complications. Therefore, a better understanding of the molecular mechanisms sustaining adipocyte

Obesity and its comorbidities have increased dramatically but treatments remain scarce, pressing the need to develop innovative therapies. In this context, targeting the energy balance by increasing energy expenditure currently holds promise to design the next anti-obesity drugs. Beyond physical act

Tight regulation of energy homeostasis at multiple levels is instrumental for organisms to cope with changes in food availability. The Central Nervous System (CNS) orchestrates a complex array of processes mediating energy intake and expenditure. Hormonal, neuronal and nutritional signals according

The regulation of feeding behavior relies on the integration of both metabolic and reward signals, which collectively ensure adaptive strategies to maintain body homeostasis. However, our modern food environment and the overconsumption of palatable energy-dense food constantly challenges such strate

ARMURE application is interested in skeletal muscle biology with specific emphasis on the regenerative process. As a major actor of the locomotion apparatus, skeletal muscles proper regeneration and homeostasis ensures individual mobility and autonomy. For decades, muscle loss of function associated

Vascular calcification associated to chronic kidney disease is a decisive risk factor of cardiovascular mortality. However, treatment options remain limited. In the laboratory, we have recently identified that calprotectin, an alarmin involved in various inflammatory and autoimmune diseases, could b

Ageing is one of the most important challenges that modern societies have to struggle in order to prevent the burden of age-associated diseases and dependency. Longitudinal studies showed that physical performance is the most predictive criterion for mortality in the elderly. Thus, deciphering the l

Hypertension is a heterogeneous, multifactorial disease that constitutes a major risk factor for cardiovascular disease. More than 870 million people worldwide develop hypertension, and around 15% of them are resistant to the therapies currently in use. It is therefore vital to identify new mechanis

Ixodes ricinus, is the most prominent tick vector of disease-causing viral, bacterial, and protozoan agents in Europe. Activities of tick salivary glands, play a pivotal role in tick-borne pathogen transmissions. Neuropeptidergic axons, originating from distinct neuronal cells, innervate several hun

Craniosynostosis (affecting around 1 in 2000 births) results in defective membranous ossification characterized by premature fusion of cranial sutures thus leading to craniofacial malformations affecting brain development. Treatments for craniosynostosis consist of extensive and repeated neurosurgic

The adrenal cortex synthetizes steroids that are vital and play a major role in many physiological processes. Therefore, deregulation of steroid secretion causes high morbidities and can be lethal. Adrenocortical adenoma (ACA) are frequent affecting 3 to 7% of the population after 50 years old where

When stressed, taking deep breaths is a universal relaxation technique that slows heart rate. Indeed, the respiratory and cardiac functions are coupled: heart rate increases during inspiration and decreases during expiration, a phenomenon called respiratory sinus arrhythmia (RSA). Enhanced RSA is ph

Cardiovascular diseases such as atherosclerosis and its consequences as myocardial infarction are the leading cause of mortality worldwide. Therefore, there is a need for new therapies to reduce atherothrombotic events. Mucosal-associated invariant T (MAIT) cells function at the interface between in

Epilepsy is brain disorder characterized by hyper-excitable neurons and tissular remodelling as neuronal death, neuro-inflammation and vascular remodelling. The Blood Brain Barrier (BBB) disruption as well as chronic neuroinflammation are known to contribute to neuronal hyperexcitability. Neuro-infl

Endothelial cells form the inner layer of blood vessels. These cells play a central role in the formation of new blood vessels in a process called angiogenesis. At adult stage, endothelial cells become quiescent while still controlling important biological processes different from one organ to anoth

The blood-brain barrier (BBB), which drastically restricts the exchanges between the brain parenchyma and the bloodstream, is at the center of dense traffic of different subpopulations of extracellular vesicles (EVs). Plasma-derived VEs are able to enter into the brain across the BBB, but the knowle