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In this project, we want to analyze the coupling between PIEZO1 and KCNN4, identify partners likely to regulate their functioning in order to propose avenues of therapeutic investigation to prevent hemolytic anemias associated with mutations in PIEZO1 or KCNN4. We characterized new mutations in the

Circadian clocks are evolutionary ancient, essential physiological mechanisms for anticipation of external cues. Initiated with a discovery of the molecular cogs of the clock in Drosophila, distinguished by a recent Nobel Prize, the last two decades have seen a dynamized field of circadian physiolog

Recent progress in modern medicine has shown that numerous pathologies are actually channelopathies (i.e. alterations in an ion channel’s structure and function). The development of cancers also involves such ion channel aberrations. Indeed, a new concept in oncological research has been developed a

BM is a muscle disease characterized by joint contractures and muscle weakness worsening with age. BM results from mutations in genes encoding one of the three a chains of collagen VI (ColVI), a component of the skeletal muscle extracellular matrix produced by interstitial fibroblasts. A still unres

The present project will investigate several breakthroughs emerging from a previous study, in which we deciphered protein-protein interactions and signalling pathways activated by a bacterial pathogen (N. meningitidis, meningococcus, the agent of cerebrospinal meningitis) to colonize brain vasculatu

TASK 1: Decipher the ECM-dependent pathways promoting the development and the progression of NAFLD in different murine models mimicking NAFLD: Focus on a CD44-OPN-HA-TNC signaling axis. By using murine NAFLD models with engineered levels of candidates (e.g. CD44, OPN, TNC), we will determine the rol

We study the underlying mechanism of the altered pathway that we identified in CS cells, where oxidative and nitrosative stress (ROS/RNS) promotes overexpression of the HTRA3 protease, which results in the degradation of the key mitochondrial DNA polymerase POLG1 responsible for replication of the o

Multiple sclerosis (MS) is a complex chronic inflammatory disease of the central nervous system (CNS) that results from immune dysregulation, due to a complex interplay between environmental factors and genetic predisposition. There is a central role for lymphocytes, especially T cells, with a funct

The exacerbated inflammatory response is a major component of metabolic syndrome and contributes to fatty liver disease progression to fibrosis. Mucosal-associated T cells (MAIT) are an abundant T lymphocyte subset in blood, adipose tissue and liver, that recognizes bacterial-derived ligands. The co

We will follow up our observations that DBI serum levels correlate with human corpulence (low in anorexia, high in obesity) and that injecting DBI into mice causes hyperphagy (and activation of orexigenic neurons) and weight gain with increased fat deposition, while its neutralization reduces feedin

Defects in Fibroblast Growth Factor Receptor 3 (FGFR3) signaling are responsible for the most common form of dwarfism achondroplasia (ACH) and the less severe form of dwarfism hypochondroplasia (HCH). These rhizomelic dwarfisms are characterized by short stature, lordosis and lumbar spinal stenosis.

Spondyloarthritis (SpA) is a group of chronic inflammatory disorders of the joint affecting primarily the axial skeleton but also peripheral limbs. Extra-articular manifestations are also considered a hallmark of SpA (e.g. inflammatory bowel diseases (IBD)). Affecting 0.43% of the adult French popul

In three work packages we shall address: 1) The capacity of luminal and vessel wall produced S1P and S1P receptors to support myogenic tone and flow-mediated dilation of resistance arteries as well as total renal vascular resistance. 2) The sources of S1P that sustain endothelial S1PR1 activation

Pulmonary fibrosis is a deadly disease for which the only therapeutic option is lung transplantation. Pulmonary fibrosis is a chronic and progressive disease characterized by the destruction of the alveoli and its replacement by a fibrotic scar. Alveolar gas exchanges are therefore disrupted thus le

Disorders of sex development (DSD) are very heterogeneous and despite intensive research over the last 30 years, only about 50% of DSDs can be explained on the molecular level. This highlights that our knowledge on mechanisms governing sex determination is still fragmented. In the project SexDiff, w

Old age, sedentary lifestyle and illness are often associated with osteosarcopenia (osteopenia and sarcopenia), which significantly increases morbidity and negatively impacts the quality of life and degree of independence of the affected person. Osteopenia is defined as a moderate loss of bone mass,

Our aims are to understand the specific response to anti-TNF-a in the gut, bone and skin focusing on environmental factors and on immune cells. Analysis are ongoing The results will open new clues for improving therapeutic approaches or prognosis markers for anti-TNF-a paradoxical effects and may im

Recently, senescent cells accumulation has emerged as a main driver of age-associated diseases. In the lab, we have recently shown that aged cardiomyocytes acquire a senescent-like phenotype characterized by persistent telomere DNA damage and activation of classical markers of senescence. In additio

Directional cell migration (i.e. chemotaxis) orchestrated by chemokines (CKs) and their receptors (CKRs) regulates organ development and plays key roles in adult physiology at the interface between tissue homeostasis and immune surveillance. Some CKs/CKrs have pivotal and non-redundant homeostatic f

Our research project aims at investigating the roles of mtCB1R in adipose tissue. We will use in vitro and in vivo models, and we will use normal and diet-induced obesity conditions. Our goal is to identify adipocyte mtCB1 as a potential therapeutic target in the treatment of pathological metabolic

Sleep apnea syndrome (SAS) is characterized by repeated upper airway collapse during sleep generating cycles of desaturation-reoxygenation leading to intermittent hypoxia (IH). Several recent studies have shown interconnections between hypoxia, circadian rhythms and epigenetics modifications. Howeve

Past stressful events can lead to sustained accumulation of reactive oxygen species (ROS). Our hypothesis is that ROS accumulation creates favorable grounds for the development of neurological disorders and co-morbidities (depression and cognitive deficits). We have shown that half of the rats expos

As a consequence of the pleiotropic effects of estrogens (E), the decline of their production by the ovaries at menopause often leads to functional disorders several climacteric symptoms (as hot flashes and night sweats, insomnia and mood instability) are due to E drop in the central nervous system

Mammalian skin is an organ containing multiple tissues (epidermis, dermis, hypodermis), multiple cellular types (keratinocytes, fibroblasts, endothelial, muscle, and immune cells but also peripheral nerve fibres) and appendages that are in permanent communication in physiologic and pathological cond

The interplay between life-history strategies, environment and the genome is a central question in biology. We are far from understanding how interactions between the environment and the genome control life history changes and how this may be constrained by internal and external factors. These life

In the ADIPOPIEZO project, we hypothesize that activation of Piezo1 in adipocytes or their progenitors constitutes a new regulatory layer in the control of adipose tissue function, having an impact on the development and/or progression of obesity and its metabolic complications. The overall objectiv

The originality of MelODies is to search biomarkers (metabolomics signatures) of organ-specific metabolic drifts occuring before the first clinical symptoms for better phenotyping early T2D onset and progression. no results to communicate yet The data obtained will lead to better design of personali

Microbioautism have the following aims: 1) Determine in mice the impact of fecal supernatant of ASD patients (FS-ASD) on gut and brain functions and associated cellular and molecular changes. 2) Identify the role of the secondary bile acids, desoxycholic acid (DCA), as a putative candidate in gut an

The general concept of this project is to demonstrate that the metabolism of polyunsaturated fatty acids modulates the development of atherosclerosis by controlling key functions of macrophages.. The combination of lipidomic and transcriptomic approaches have identified a tightly regulated set of ge

The challenge of this project was twofold: (i) to broaden our in vivo understanding of the observed pheonomen of Enterobacteria-fungi interaction; (ii) to identify the effectors and mechanisms. This collaborative project was initiated following the publication of an article by the coordinator and p

Autosomal polycystic kidney disease (ADPKD) is responsible for 10% of end-stage renal disease cases. The disease is mainly due to PKD1 (encoding polycystin 1) loss of function mutations, which lead to the formation of proliferating cysts that progressively replace normal renal tissue. While ADPKD pa

Hypothesis: NGAL is involved in blood pressure control via the modulation of renal Na transport. Moreover targeting NGAL may have several beneficial effects in CV and renal comorbidities related to hypertension. Our objectives are to 1) determine the underlying mechanisms, 2) study the correlations

The goal of the PaiNetWork project is to characterize the phenotype, the function, and the synaptic connectivity of the neural microcircuits underlying mechanical allodynia at the peripheral, segmental, and supra segmental levels, under neuropathic or inflammatory conditions. Behavioral results meas

The main objective of this project is to elucidate the mechanisms of life-threatening ventricular arrhythmias involved in sudden cardiac death (SCD), which accounts for about 15% of casualties worldwide. SCD may happen in a diseased heart, but also in structurally normal hearts where a channelopathy

Current understanding of pediatric sarcomas heterogeneity is limited to intertumor heterogeneity, mostly focused on histological and/or molecular subclassification based on -omic profiling. But, such subclassification may not capture the full tumor spectrum of RMS and OS as suggested by recently pub

We propose the following hypothesis: in dystrophic muscle, new crosstalks are established between activated muscl stem cells, macrophages and fibroadipogenic precursors that involve paracrine and cell-to-cell signaling pathways to promote fibrosis. Our analysis of the fibroadipogenic behavior and fu

SAHARRA aims to use single-cell transcriptomics to unravel the sequences of molecular events that control the balance between the distinct cell types of the airway epithelium and their deregulation in asthma. Asthma is a chronic respiratory disorder characterized by airflow limitation, chronic infl

The non-alcoholic fatty liver disease (NAFLD) is rapidly expanding worldwide as its incidence is correlated with the obesity pandemic. NAFLD encompasses a spectrum of pathologies ranging from simple steatosis characterized by triglyceride (TG) accumulation in hepatocytes, to non-alcoholic steatohepa

The Epi-Dev project will investigate the epigenetic and transcriptional mechanisms underlying lymphoid lineage specification in mammals. Our consortium will use a comparative human/mouse experimental strategy combining functional analyses and high throughput transcriptomic and epigenomic studies. Hu

Gonad development in mammals depends on a cell fate decision that occurs in a bipotential somatic cell to commit to Sertoli (male) or granulosa (female) cells. This is a classic but poorly understood process in biology. Data suggest that mammalian sex-determination (SD) involves complex and mutually

Ammonia-nitrate fertilizers are responsible for the release of nitrous oxide and for water pollution. Reducing the use of nitrate fertilizers without affecting plant yields and product qualities could be achieved by increasing the nutrient-recycling performances in plant organs especially by improvi

Background. Aortic valve replacement is the sole therapeutic solution to improve outcomes in patients with aortic stenosis. AVR is commonly performed during on-pump cardiac surgery, whereas trans-catheter aortic valve implantation is increasingly performed in patients with high-risk for surgery comp

Bone is a complex and dynamic tissue constituted by a collagen matrix filled in with crystal of hydroxyapatite. Chondrocytes, the cells of cartilage, are involved in bone biology and more precisely during the bone growth. In the endochondral ossification, the skeletal cartilage templates are replace

PIK3CA-Related Overgrowth Syndromes (PROS) is a genetic disorder due to somatic gain of function mutations of the PIK3CA gene. This rare condition has no specific treatment and a poor survival rate. We recently developed a genetic mouse model of PROS that recapitulates the human disease and identifi

Context: By 2020, the prevalence of heart failure with preserved ejection fraction (HFpEF) will turn into the most common heart failure phenotype with a mortality rate similar to the one of heart failure with reduced ejection fraction (HFrEF). Nevertheless, in contrast to HFrEF, there is a lack of c

Rupture of intestinal epithelial barrier (IEB) integrity is associated with a variety of gastrointestinal disorders. In particular IEB permeability is increased in inflammatory bowel disease or obesity and strengthening of the IEB has been associated with better clinical outcomes. Our preliminary da

Inflammation is established as a causal factor in developing type-2 diabetes (T2D). We reported that inflammation in T2D arises through the transcription factor Interferon regulatory factor (Irf)-5 in adipose tissue and liver macrophages (Dalmas et al 2015; Alzaid et al 2016). Here, I present prelim

Recent advances in healthcare technologies are associated with a substantial increase of lifespan. A crucial challenge ahead is to promote healthy aging, which requires a better understanding of age-associated pathology mechanisms. A key determinant of frailty is the loss of muscle mass and function

The worldwide incidence of Chronic Kidney Disease (CKD) has reached epidemic proportions and is a major health care burden. A key medical challenge is to provide new therapeutic tools to tackle CKD progression. We think our research has the potential to establish another pathway as a valid drug ta