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Identification of new membrane receptors for daily retinal phagocytosis – Rephago
At the back of the eye lies a monolayer of cells essential for vision: the retinal pigment epithelium (RPE). Apical microvilli from these polarized cells make close contact with the photosensitive photoreceptor outer segments (POS). POS are constantly renewed to fight the high levels of oxidative da
ROLE OF THE PHOSPHATE EXPORTER XPR1 IN VASCULAR CALCIFICATION – CALCIPHOS
Phosphate is one of the key minerals in the body that participates in the synthesis of nucleic acids and membranes, bone and tooth mineralization, energy production (ATP) and signal transduction. Phosphate is present in blood, cerebrospinal fluid (CSF) and cells, and its concentration is tightly reg
Lymphatic drainage, Immune cell recirculation and brain repair after stroke – BrainWash
Stroke is a leading cause of death, killing approximately 30.000 French people each year. Stroke occurs when blood flow to an area of the brain is cut off, causing death of oxygen- and nutriment-deprived brain cells downstream of obstructed blood vessels. Stroke also causes inflammatory cell accumul
Podocytic Immune-Like Receptors: Role of Common gamma Chain / STAT5 signaling in Podocytopathies – PODOGAMMAC
Kidney diseases affect 10% of the population and represent a global health burden. End-stage renal disease (ESRD) is also associated with a high incidence of cardiovascular events, elevating further the cost for society (€4 billion a year in France). Glomerular disease is one of the main causes of E
Unraveling the Functions of the CTL2 in Thrombosis – CLINT
Venous thrombosis (VT) is the third leading cause of cardiovascular death in industrialized countries. Using a genome wide association study (GWAS) approach we have recently identified SLC44A2 as a new susceptibility gene for VT, the Arg154 isoform being associated with an increased risk. The SLC44A
Deciphering interactions between megakaryocytes and their bone marrow environment, a prerequisite to implement in vitro platelet production for transfusion – MEGAPLATPROD
A major public health issue comes from the increasing needs of platelet concentrates to be transfused in older adults, in individuals under anti-cancer therapy, or in bone marrow graft receivers during the recovery period. Despite the implementation of safety procedures, presence of unsuspected path
In vivo analysis of muscle stem cells vascular niche – MyoStemVasc
Skeletal muscle regenerates after injury, due to the satellite cells (SCs), the muscle stem cells that activate, proliferate, differentiate and fuse to form new myofibers. While SCs are indispensable for regeneration, there is increasing evidence for the need for an adequate cellular environment for
EPAC1: A new therapeutic target in chronic kidney diseases – EPACK
Chronic Kidney Disease (CKD) is a major burden of public health affecting millions of people around the world. Even though many aspects of the complex mechanisms orchestrating progression of renal disease have been identified, so far there is no specific treatment to slow down or prevent CKD progres
Regulation of biliary homeostasis by the scaffold protein EBP50 – EBPatobile
Scaffold proteins assemble and orchestrate cellular events such as the regulation of integral membrane protein activity, e.g. transporters, receptors, and signal transduction pathways. EBP50 (Ezrin-radixin-moesin (ERM)-Binding Phosphoprotein 50)/NHERF1 (NHE3 exchanger Regulatory Factor 1) is a PDZ-s
Contribution of the Vascular Smooth Muscle Cell-associated Type I cytokine receptors to Pulmonary Arterial Hypertension: At the interface between inflammation and pulmonary vascular remodeling – CoVeR
Despite major therapeutic advances, pulmonary arterial hypertension (PAH) is still a lethal condition without cure at this time. The associated costs to this disease’s care represent a major burden to the healthcare system and a public health concern. Importantly, no therapeutic agent targets the ma
Nuclear Receptor Coregulators in Spermatogenesis – CoRNuSperm
Nuclear receptors (NR) are ligand-dependent transcription factors that activate or repress transcription of genes critical to biological processes such as development, reproduction, and homeostasis. Apart from the normal physiology, NR have been identified to play a role in many pathological process
Controlling fate determination of Adipose tissue-derived Progenitors to improve obesity-related metabolic disorders – CAPTOR
CAPTOR capitalizes on previous findings and proposes to explore white adipose tissue (WAT) remodeling and the origin of fibrosis accumulation in obesity. Its overall concept is based on maintaining the health of WAT depots to attenuate obesity progression and development of comorbidities. Obesity-in
Brain bile acid signaling in metabolic control – BABrain
Obesity and its associated diseases, such as type 2 diabetes, are a worldwide health concern. The most effective and durable therapies for the treatment of obesity nowadays involve surgical rather than behavioral or pharmacological interventions. Patients that undergo bariatric surgery not only los
BMP9 as a major regulator of vascular tone in Pulmonary Arterial Hypertension: a promising new therapeutic target – B9inPAH
Cardiovascular diseases are a major economic burden on health care systems and represent one of the leading causes of global mortality and morbidity. These recent years have demonstrated the fundamental role played by BMPs (Bone morphogenetic proteins) in cardiac and vascular development, and that d
Dysfunctions of Human Muscle Stem Cells in Sepsis – PUSHUPS
Sepsis is a general, uncontrolled and systemic inflammation due to an infection. In serious cases of sepsis (called septic choc) mortality can range between 40% and 50% and concerns 200.000 people in the USA every year. Nowadays patient management is getting better and mortality diminishes, how
Deciphering the role of the transcription factor E2F1 in pancreatic beta-cell identity and plasticity – BETAPLASTICITY
Type 2 Diabetes (T2D) is characterized by inadequate pancreatic insulin secretion in the face of peripheral insulin resistance. In France, the global prevalence of diabetes is estimated at 6%, with an annual increase rate of 5%. Genome-wide association studies, as well as post-mortem studies of diab
Validation of new therapeutic targets to prevent collagen accumulation in cardiac fibrosis: the procollagen C-proteinase enhancers – CardiActiV
Heart failure is a major cause of hospitalization worldwide, with 50% of the patients dying within 5 years of diagnosis. Its triggers (myocardial infarction, hypertension, coronary artery disease etc.) induce an active process of tissue response to injury often leading to aberrant tissue remodeling
Tight junctions: from structure to treatment – T-JUST
Any inner and outer body surface is covered by epithelia. Epithelia are shaped by a layer of cells that, at the same time, form a barrier against the loss of salts and water, and transport salts and water in a coordinated manner. Transport across epithelial layers uses two pathways: the transcellula
Targeting Matriptase-2 to develop new therapeutic strategies for iron related disorders – MTREAT-2
Iron is essential for living organisms but excess iron is toxic. Therefore, body iron homeostasis must be tightly maintained since any disturbance may have severe consequences. Iron-related disorders encompass iron-restricted anemias, inherited anemias with ineffective erythropoiesis and genetic iro
Autophagic regulation of memory and brain longevity – memorautophagy
Normal brain aging is characterized by a decline in cognitive functions that develop around midlife. One of the most commonly affected regions of the brain is the hippocampus, leading to learning deficits and memory impairments. With increased life expectancies in developed societies, the number of
Understanding the remodeling processes during atrial fibrillation stabilization for improved therapeutics – UNMASC
Atrial fibrillation (AF) is the most common sustained form of cardiac rhythm disturbance occurring in 1 to 2 % of the global population. In 90% of paroxysmal cases, it is ignited by ectopic foci located within the pulmonary veins (PV) region. Those ectopic foci may trigger reentries that promote AF
Role of Vasorin in the kidney, bone and arterial crosstalk. – Vasorin
A cross-talk between bone homeostasis and the kidney has been revealed by the association of chronic kidney disease (CKD) and mineral bone disorder (MBD). The abnormalities observed in CKD-MBD also contribute to vascular calcification, a major cause of mortality in patients undergoing dialysis. This
Pediatric and Adult Plasticity of Intestinal SMCs – PAPIS
Chronic constipation constitutes an extremely frequent symptom of consultation in the pediatric discipline. A study undertaken by French High Official Health organization in 2005 evaluates between 300 to 600,000 the number of children (from 0.5 to 8 years old) suffering each year from constipation a
Hedgehog signalling in lifespan determination and neuroprotection in Drosophila – HHneuro
In humans, ageing is accompanied with an increase in prevalence of neurodegenerative diseases (Bishop et al, 2010). On a cellular level, ageing has been associated with various defects which culminates in a loss of irreplaceable cells, including neurons and supporting glial cells in the brain leadin
Nutrient-dependent lysosomal functions in type 2 diabetes – LYSODIABETES
Proper nutrient sensing is crucial in multicellular organisms. In mammals upon feeding, the pancreatic ß cell mainly senses increasing glucose levels and secretes insulin that acts to induce anabolic pathways in different organs. Inversely, the ß cell decreases insulin secretion to suppress these an
Glucose transport via the Glucose-6-phosphase – TransGlucoPase
Obesity and Type 2 Diabetes are now considered as worldwide epidemics. To prevent and/or to cure these pathologies, the regulatory mechanisms of biological processes involved in their development need to be characterized. Among these processes, endogenous glucose production (EGP) is a crucial functi
New TARGETs for osteoporosis: from mesenchymal stem cells to the regulation of osteogenesis and BONE mass – TARGETBONE
Osteoporosis, the major cause of fractures, results from an imbalance between bone formation and bone resorption. While accelerated bone resorption characterizes postmenopausal bone loss related to estrogen failure, reduced bone formation is responsible for idiopathic and age-related bone loss. The
Protection of intestinal stem cells under stress: the cell, the niche and the microbiota – i-Stress
Maintenance of intestinal stem cells (ISC) is key to ensure epithelial homeostasis and efficient repair following tissue injuries by any stress, be it infectious, physical or chemical. Under stress conditions, ISC may either die or survive thanks to powerful cytoprotective mechanisms that are either
Enteric Nervous System Effects on Human Intestinal Development. – SyNEDI
The neonatal period is critical to the development of the gastrointestinal (GI) tract and is being recognized as a possible origin of common diseases that emerge at birth or late in life. Evidences have identified the enteric nervous system (ENS) as a key regulator of GI functions. However, the link
POrtal Glucose SIgnal to counteract DIABetes – POGSIDIAB
Obesity and diabetes are characterized by deregulations of endogenous glucose production. Three organs, the liver, kidney and intestine can produce glucose in the blood because they have the key enzyme: glucose-6 phosphatase (G6Pase). While hepatic glucose production is deleterious, intestinal gluco
Control of mitochondrial energy metabolism by the ubiquitin/proteasome system. – Ubinergy
Mitochondria are important intracellular organelles which participate to the cellular health by providing energy for all biological functions. This metabolic function of mitochondria requires a fine regulation. Otherwise, the energy homoeostasis is altered which lead to severe physiological conseque
Understanding the Mechanisms of Human Gonadal Development – MGonDev
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 switch is a classic but poorly understood question in biology. Data suggest that mammalian sex-determination (SD) involves complex mutu
Role of iron in the pathogenesis of NASH – IRONASH
Nonalcoholic fatty liver disease (NAFLD) affects 30% of the world population. A subset of patients progresses to nonalcoholic steatohepatitis (NASH), a more severe form of the disease, which can evolve to cirrhosis and hepatocellular carcinoma. There is currently no treatment available to limit dise
Targeting the IL-20/IL-22 balance to restore pulmonary, intestinal and metabolic homeostasis after cigarette smoking and unhealthy diet – TheraSCUD2022
Cigarette smoking and unhealthy diet (SCUD) are major behavioral risk factors that contribute to the alarming rise in non-communicable inflammatory diseases. Cigarette smoking is often associated with unhealthy patterns of nutrient intake thus increasing the risk of developing metabolic disorders no
ß-catenin-mediated epigenetic control of the imprinted DLK1/Dio3 locus in liver – DLK1-EPILIV
Liver is a vital organ, ensuring hundreds of metabolic functions and thus finely specialized for its metabolism, which consequently need from birth to adulthood to acquire its metabolic zonation and gradually enter into quiescence. Nevertheless, in response to liver damages, hepatocytes have the cap
T follicular helper cell in atopic march: innate control and pathogenic role – Tfh-Atopy
Atopic diseases, including atopic dermatitis (AD) and asthma are closely related allergic diseases, sharing common features of “atopy”, with IgE production and type 2 allergic inflammation. Affected individuals often experience the progression from AD to asthma, known as the “atopic march”. Allergen
Autocrine/paracrine CXCL12/CXCR4-CXCR7 signaling within the bone marrow osteo-vascular niche: impact on lymphoid specification and commitment of hematopoietic stem cells – OSTEOVALYMPH
Hematopoietic stem and progenitor cells are responsible for replenishing immune cells and reside in bone marrow (BM) endosteal and vascular niches. The divergence of lymphoid and myeloid lineages occurs at the multipotent progenitor (MPP) stage. Although numerous studies focus on molecular regulatio
Role of MAIT cells in type 1 diabetes in humans and mice – Diab1MAIT
Type 1 diabetes (T1D) is an autoimmune disease resulting from the destruction of ?eta pancreatic cells by the immune system. Many studies have been focused on the analysis of autoreactive T cells however innate immune cells are also involved in the pathogenesis and the regulation of T1D. Mucosal Ass
Genome mapping and biological characterisation of metabolomic biomarkers underlying shared genetic risk of asthma and obesity – MetabAsthma
Evidence from genetic and molecular investigations strongly suggests an etiological relationship between asthma and obesity. Genome-wide association studies (GWAS) have identified common risk loci for these diseases, which share alterations in immunological mechanisms and changes in both gut microbi
Regulation of NKCC2 and NCC by Protein–Protein interactions: From salt losing tubulopathies to salt sensitive hypertension – Pheno2Geno
Hypertension in one of the most common diseases affecting human population. It is a major risk factor of cardiovascular morbidity and mortality. The kidneys play an essential role in short- and long-term control of blood pressure. Analyses of monogenic syndromes, has allowed to link hypertension to
Maintenance and role of Kupffer cells in steatohepatitis – TARGETKC
Nonalcoholic fatty liver disease (NAFLD) is the most prominent form of liver disease in the western world, affecting approximately onethird of the population, and is projected to become a major clinical and economic burden worldwide within the next decade. Chronic inflammation favors the perpetuati
Targeting cardiometabolic pathways to reset monocyte clock – MOTACARD
Cardiovascular diseases (CVD) are the leading cause of death worldwide with 17 millions deaths every year and represent a major public health challenge. Atherosclerosis is the main cause of CVD characterized by the accumulation of lipids and leukocytes in the lumen of arteries and causing their narr
Role of HMGB1 protein during metabolic stress – HOLISTic
The incidence of obesity worldwide has increased drastically during last decades, consequently obesity and related disorders now constitute a very concerning international public health issue. The World Health Organization estimates that over 1,4 billion adults are in overweight and of these, 500 mi
Impact of Fatty Acid Metabolism in Adipose Tissues and Liver on Insulin Resistance – HepAdialogue
DDysregulation of fat metabolism in liver and adipose tissues is a hallmark of insulin resistance. White and brite/beige adipose tissues, and liver produce proteins and lipids with systemic action on insulin sensitivity. The regulation of the pathways involved in the synthesis, release and use of fa