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Origin and role of synovial macrophage heterogeneity in rheumatoid arthritis – SyMAC
Macrophages are mononuclear phagocytes that play crucial roles in development, tissue homeostasis, induction and resolution of immune-mediated inflammatory responses. The imprinting by the niche has considerable influence on macrophage identity and self-maintenance capacity. In contrast to many orga
Identification of the mechanobiological factors involved in platelet formation – PlatForMechanics
The mechanisms of cell differentiation are crucially dependent on the mechanical properties of the BM microenvironment and had been neglected in platelet formation, hampering large-scale platelet production for transfusion purposes. This limitation highly underscores the need to further understand h
PW1+ stromal Cells In Cardiac Fibrosis – PACIFIC
Heart failure (HF) is a major life-threatening disease affecting more than 1 million people in France and is associated with a high mortality rate. While the etiology of HF is diverse (coronary artery disease, myocardial infarction, hypertension, aging, etc.), they are all associated with aberrant m
Origin and function of the pituitary generator of GH pulses – GH-Gen
A current challenge in physiology/pathology is translating cell-transduction processes identified in vitro into the living organism, especially where cell-cell interaction and dynamics have key functional roles. The pituitary gland, regulating a range of essential physiological functions, exemplifie
Underexplored vps34-Regulated Autophagic flux IN Chronic pancrEatitis. – RADIANCE
It is widely accepted that autophagy, the intracellular degradation system, plays a key role in the exocrine pancreas, as acinar cells possess a tremendous capacity to synthetize secreted protein. RADIANCE will aim to demonstrate that the class III PI3K Vps34-regulated autophagic flux allows the
Role of TGF beta family members in muscle wasting : towards innovative therapeutical approaches – TGFMyo
Hypothesis: We make the hypothesis that chronic TGFß activation not only involves imbalance muscle catabolism/anabolism (excessive proteolysis leading to muscle fibers shrinkage) but also many poorly explored aspects of muscle biology (energy metabolism, calcium homeostasis, regenerative capacities,
Steroidogenomics analysis of adrenal steroid excess – STEROMICS
The morbidity and mortality associated with excess adrenal steroids is significant in the absence of treatment.Getting a better understanding of the mechanisms of these disturbances would allow to manage them more effectively and generally to better understand frequent pathologies in which disturban
Role of mitochondrial cannabinoid type 1 receptor in hypothalamic circuits and its interaction with mTORC1 pathway during obesity. – MitObesity
Obesity is a major health problem worldwide. Despite the human and economic costs of obesity and of its associated metabolic disorders, a very limited number of anti-obesity treatments are currently available, highlighting the insufficient knowledge of the biological mechanisms regulating energy bal
Impact of LUng MIcrobiota in vascular remodeling and pulmonary arterial hypertension: potential for innovative biotherapeutic target – LUMI
Pulmonary Arterial Hypertension (PAH) is a rare, incurable and deadly disease of the pulmonary vessel. It is defined by an elevation of pulmonary arterial pressure, due to progressive and obstructive remodeling of small pulmonary arteries, leading to right heart failure. Existing treatments target v
Lipopeptides produced by the microbiota: from hypersensitivity to therapy in irritable bowel syndrome – LiBacPain
Irritable bowel syndrome (IBS) is characterized by abdominal pain and/or discomfort, bloating and bowel dysfunction such as constipation, diarrhea, or mixed bowel patterns. While IBS is not a life-threatening disease, it can be responsible for an important alteration of quality of life (QoL) affecti
Deciphering the dynamic of transcription during meiotic prophase I – MEIOSIL
Meiosis is the cellular process that allows the formation of haploid cells central to sexual reproduction and fertility. In mammals, only germ cells are able to undergo meiotic division and form the gametes (egg or sperm). Two intriguing events are reported at the time of meiotic entry: i- a genome
Role of mucin-degrading bacteria and CARD9 in IgA nephropathy – MUCIGAN
IgA nephropathy (IgAN), one of the most common kidney diseases worldwide, is associated with microbial infections at mucosal sites and represents a major cause of renal failure. Its pathogenesis involves IgA1 complexes containing degalactosylated IgA1 (Gd-IgA1), autoantibodies against IgA1, and solu
TimE frame ControL of Inflammation by canonical and non-canonical autophagy to Prevent fatty liver diSease progrEssion – ECLIPSE
In Europe, 25 million individuals have non-alcoholic steatohepatitis (NASH). NASH has the potential for cirrhosis, cirrhosis decompensation and ultimately organ dysfunction and death. There is no approved treatment for NASH and its complications. Sustained inflammation, in particular originating fr
AHR activation and mechanisms of cell alteration in myasthenia gravis model – ATM
Numerous groups have demonstrated that environmental factors (endocrine disruptors) through their nuclear receptor, the Aryl hydrocarbon receptor (AhR), activate transduction pathways that regulate the immune system and contribute to autoimmunity. Research groups evidence that prenatal or early-life
Molecular mechanisms of sensitization to allergic asthma and therapeutic innovation – Innovasthma
Asthma is a highly prevalent disease with increasing socioeconomic burden, whose most frequent allergic cause is sensitization to house dust mite (HDM). High-throughput sequencing of HDM extracts has revealed the presence of Gram-negative bacteria that may likely arise from their gastrointestinal tr
Defining the severe paediatric asthma endotype: an integrated approach combining phenotypic analyses related to immune, metabolomic, and microbial features – SevAsthma-children
Asthma is a chronic disease affecting approximately 235 million people worldwide, and the number is rising. Asthma is not just a public health problem for developed countries; its incidence is also elevated in developing countries. Asthma concerns all age groups, but often starts in childhood. Sever
KCNK3 channel A new therapeutic target in Pulmonary Arterial Hypertension – KAPAH
Pulmonary arterial hypertension (PAH) is a devastating disease, consequence of a progressive narrowing of the distal pulmonary arteries, resulting in high pulmonary vascular resistance, right ventricular hypertrophy (RVH) and ultimately right heart failure. The pathobiology of PAH is multifactorial
Targeting the IRE1 branch in steatohepatitis – IRE1inNASH
The incidence of Non-alcoholic fatty liver disease (NAFLD) is constantly increasing, owing to the obesity epidemic. The first step in the course of NAFLD progression is hepatic steatosis. Steatosis can progress to nonalcoholic steatohepatitis (NASH), a progressive disease defined as a combination of
Integrated genomic characterization of Growth Hormone-secreting Pituitary Adenomas – INTE-GRAL
Somatotroph pituitary adenomas are responsible for chronic Growth Hormone (GH) excess leading to gigantism during childhood and acromegaly in adulthood, both of which are associated with significant morbidity and, if untreated, increased mortality. The first line treatment of somatotroph adenomas, w
Study of the SYK signaling pathway in chronic inflammatory diseases – INFLAMMASYK
Activation of innate immune cells by Pathogen-associated molecular patterns (PAMPs) and Damaged-associated molecular patterns (DAMPs) via Toll like receptors (TLRs) signaling is a key mechanism in the pathogenesis of chronic inflammatory diseases. Spleen tyrosine kinase (SYK) emerges as a novel regu
X-Linked Hypophosphatemia: from impaired mineralization process to skeletal manifestation treatments – HYPOSKEL
Inherited genetic disorders affecting calcium (Ca) and phosphate (Pi) mineral homeostasis cause severe disabling conditions that manifest as abnormal levels of blood Ca and/or Pi, skeleton growth impairment, with bone and tooth abnormalities. Investigation of the pathogenesis of these monogenic diso
Mechano-electric coupling in the healthy and pressure-overloaded right ventricular outflow tract – MEGaVOLT
Cardiovascular diseases are the leading cause of death in Europe, accounting for 46% of all deaths1. Among cardiac-related deaths, 50% are sudden and caused by a severe arrhythmia, ventricular fibrillation. However, mechanisms leading to ventricular fibrillation and sudden cardiac death (SCD) are po
Autophagic regulation of kidney physiology upon shear stress – MECHANOPHAGY
Autophagy is a lysosomal degradation and recycling pathway that controls the quality and quantity of cytoplasmic material. Autophagy requires the formation of a double-membrane vacuole called the autophagosome that sequesters proteins and other cytoplasmic components to be delivered into the lysosom
Understanding the dynamic of the vascular niche in pulmonary hypertension (PH). Matrix reprogramming forces PH. – MatriPHate
Pulmonary hypertension (PH) is a chronic disease of the pulmonary vasculature with increasing significance worldwide, characterized by increased pulmonary arterial pressures, right ventricular failure, and often death. Little is known about molecular controls underlying this chronicity of PH develop
Role of the anti-aging factor alpha-klotho in osteoarthritis – KLOTHOA
Osteoarthritis (OA) is the most prevalent joint degenerative disease with a huge unmet medical need. So far, only painkillers are used in clinic and alternative long-term innovative therapies are required. Various clinical OA phenotypes have been described including post-traumatic and age-associated
Modelling cachexia in drosophila – CADRO
Cachexia, or dramatic and rapid wasting of muscle and adipose tissue that cannot be compensated for by increased energy intake, is a devastating condition associated with many chronic diseases. It is estimated that 80% of patients with advanced cancer will suffer from this condition. The associated
GAG synthesis and skeletal dysplasia: role of SLC10A7 – SKELGAG
.Skeletal dysplasias with multiple dislocations (SDM) are severe disorders characterized by dislocations of large joints, scoliosis and pre and postnatal growth retardation. More than 10 recessive disorders have been described so far and the majority of them have been linked to pathogenic variants i
Role of PARylation on cardiovascular disease in progeroid syndromes – PAR-AGING
Progeroid syndromes (PSs) are rare genetic disorders mimicking clinical and molecular features of aging. Among all of the clinical features associated with premature aging, the cardiovascular disease is the cause of death in almost all patients. Despite its great importance, investigation of the art
Elucidate the role played by Rab4b-depenant endocytosis in hepatocyte glucose metabolism regulation – Rab4LiverMetabolism
Failure in glycemic control by hepatocytes is a pivotal event in the development of metabolic diseases such as type2-diabetes, NAFLD and NASH. However, although the complex network of transcription factors and enzymes allowing hepatocytes to reorganize their metabolic pathways for glucose homeostasi
Central and complex roles of the transcription factor E4F1 in pyruvate metabolism – PyrE4F
Our current research program aims at exploring the interplay between transcriptional networks, chromatin organization and cellular metabolism, and at investigating how perturbations of these networks lead to the development of human diseases. One of these networks involves E4F1, a multifunctional pr
Target skeletal stem cells in periosteum for skeletal regeneration and diseases – PERISTEM
Musculoskeletal diseases and disorders affect 1 in 7 people and represent the second cause of disability worldwide. Impaired bone healing can be associated with severe trauma, osteonecrosis, tumour resection and bone diseases. The societal cost of these repair delays is very high due to heavy surger
Role of chronic intermittent hypoxia on cell senescence and age-related diseases – OSAGING
Obstructive sleep apnoea (OSA) syndrome is a common disorder (6-12 % of adults) in which recurrent apnoea and hypopnoea produces repeated hypoxaemia episodes followed by re-oxygenation. These hypoxaemia/re-oxygenation cycles induce oxidative stress, a major contributor to OSA-related morbidity and m
Acute effect of metformin on intestinal sodium-glucose co-transport / – MET-INTESTIN
Acute effect of metformin on intestinal sodium-glucose co-transport Metformin is widely used to treat type 2 diabetes but its mechanisms of action remain uncertain. Converging evidences now indicate that this non metabolized agent might primarily act in the gut. Preliminary data obtained by the
Role of the estrogen receptor alpha in of flow (shear stress)-mechanosensing in vascular endothelial cells: pathophysiological consequences – EstroShear
Beside large conductance arteries, arterioles, the small / resistance arteries (RAs) located upstream capillaries control blood delivery to tissues at relevant flow and pressure. Disorders in their structure and function can raise downstream capillary pressure, which induces organ damage, and can pa
ENTERIC NERVOUS SYSTEM NEURONS AS A TARGET TO TREAT TYPE 2 DIABETES: ROLE OF BACTERIAL BIOACTIVE LIPIDS – ENDIABAC
Type 2 diabetes (T2D) is a major public health problem with 3.5 million of diabetic patients in France, and more than 300 million all over the world. T2D is now considered as an epidemic disease associated with co-morbidities (cardiovascular dysfunction, neuropathy,…) that cost more 13 billion €/per
Coeliac disease: mechanisms of resistance to gluten-free diet – COELAR
Background: This project is part of our long-term effort to elucidate how chronic intestinal inflammation driven by dietary gluten in patients with coeliac disease (CD) can ultimately lead to the development of enteropathy-associated T lymphoma (EATL), a rare but most severe malignancy. We have demo
Disrupting abnormal protein-protein interactions to correct the functional defect of F508del-CFTR – CFTRgateway
Protein misfolding diseases (PMDs) are associated with either aggregation of misfolded proteins leading to toxic gain-of-function phenotypes or with protein degradation leading to loss-of-function phenotypes. Cystic Fibrosis (CF) is an example of a loss of function resulting from genetic mutations w
Phosphoinositide kinases: new regulators of platelet granule biogenesis, integrity and secretion – BIOSEC
Platelet granules are key elements for many platelet functions through secretion of bioactive molecules. The knowledge of mechanisms involved in different steps of platelet granule biology (from biogenesis, the maintenance of integrity to secretion) remains still limited, which impedes our understan
How do estrogens orchestrate fertility and energy homeostasis in the central nervous system: mechanistic insights in the membrane and nuclear effects of the Estrogen Receptor alpha (ERalpha) – BENEFIT
The obesity epidemic continues unabated and currently available pharmacological treatments are not sufficiently effective. The consistent worldwide disparity in prevalence of severe obesity strongly suggests that biological factors, i.e. physiological sex differences, in particular sex hormones cont
Role Of bronchial Smooth muscle on Asthma Exacerbations – ROSAE
Asthma is a very frequent airway disease that affects 6 to 20% of the population of western European countries. In the European Community Respiratory Health Survey II, the majority of asthmatic patients remains uncontrolled. Whereas asthma mortality has decreased within the last 30 years, uncontroll
Retinoid acid pathway and fibrocalcification in Aortic Valve Stenosis – RETINAVS
Fibrocalcific Aortic Valve Stenosis (AVS), characterized by a narrowing of the aortic valve opening, leads to an obstacle to the blood flow through the aortic valve during left ventricular ejection. In industrialized countries, this disease affects 2 to 6% of people aged above 65 years and its preva
Sex-specific tissue homeostasis and its impact on adrenal diseases – Sex-Specs
The evolution of opposite sex in living organisms has generated significant dimorphism between males and females. As such it is not surprising that predisposition to and progression of diseases also differs in many organs. Sex bias is particularly striking in the adrenal cortex and diseases, such as
TargEting TREM-1 Receptor in Abdominal Aortic Aneurym – TETRAAA
Non-syndromic abdominal aortic aneurysm (AAA) is one of the leading causes of cardiovascular death particularly in men and women aged over 60 years and its incidence will increase during the next 30 years. The pathophysiology of AAA is complex, including elastin degradation, collagen remodeling, smo