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Homeotic transformation of the jaw and central respiratory disorders in Auriculo-Condylar syndrome – CranioRespiro
Neural crest cells are an embryonic cell population that gives rise to a diverse range of tissues. Endothelin signalling is essential for the development of several of these, including the lower jaw. Recently, we identified mutations in genes of the endothelin pathway (EDN1, PLCB4, GNAI3 and EDNRA)
Role of Mucosal Associated Invariant T cells in Obesity in patients and mouse models – OBEMAIT
Recent advances in understanding the etiology of obesity and type 2 diabetes (T2D) have established the involvement of the immune system. Converging data highlighted the role of innate-like T cells such as NKT and Mucosal Associated Invariant (MAI) T cells, which act as a first line of T cell respon
LIPA as a promising target to fight cardiometabolic diseases – LIPOCAMD
Background: The metabolic syndrome defines a group of criteria confering high cardiovascular risk in patients, and represents one of the major public health challenges worldwide. Chronic low-grade inflammation as a common feature in this syndrome has been associated with excess adipose tissue. Thus,
Using genetic markers of vascular risk factors as a tool to better understand their relationship with cognitive decline and dementia in the community – VASCOGENE
With expanding longevity, the number of dementia cases is increasing worldwide and is expected to triple over the next 40 years. Delaying the onset of dementia and Alzheimer disease (AD) by just a few years could have a major impact on their prevalence at the population level. To date no effective m
The role of semaphorin-signaling in the neuroendocrine control of reproduction – RoSes and GnRH
Reproduction in mammals is under the control of the hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH). GnRH-secreting neurons, like primary olfactory neurons, originate in the olfactory placode. Early in development, the olfactory neurons send their axons to the rostral forebrain (whic
Circadian regulation of O-GlcNAcylation by the nuclear receptor Rev-erbalpha – OGlcRev
Metabolic diseases show a steadily increasing prevalence in all countries and constant, unbalanced dietary inputs are major culprits in triggering these debilitating chronic pathologies. It is also widely acknowledged that even short term perturbations of the circadian rhythm (CR) are a causative fa
NOTCH3: A NEW MEDIATOR AND TARGET OF THERAPY FOR CHRONIC KIDNEY DISEASE – Active Notch
Chronic Kidney Disease (CKD) is a major burden of public health affecting millions of people around the world. Even though significant progress has been made and many aspects of the complex mechanisms orchestrating progression of renal disease have been identified, it still remains a fact that there
Cell senescence in chronic lung disease – SENEC
Cellular senescence – defined by a stable arrest of the cell cycle coupled to stereotyped phenotypic changes – might play a causal role in a variety of lung pathologies, among which chronic obstructive pulmonary disease (COPD), predicted to be the third cause of death worldwide in 2020. COPD is char
Modeling Monogenic Diabetes – MDM
Type 2 diabetes (T2D) affecting 300 million individuals worldwide and responsible for severe co-morbidities and early mortality, is a main health challenge of the 21st century. Whilst the environment is the key contributing factor at the population level, genetic factors are the major determinants o
Role of the Progerin-PLA2R1 axis in cellular senescence and aging – PROPLAGE
Cellular senescence is involved in numerous physio-pathological conditions, most of them being altered during aging. Senescence response is activated by numerous cellular stresses and it results in the acquisition of a specific secretome and is characterized by a stable proliferation arrest. This pr
Transfer of MSC mitochondria to T lymphocytes: impact on T cell metabolism, phenotype and recirculation in autoimmunity – MitoStem
Mesenchymal Stromal Cells (MSCs) were firstly described in the bone marrow but are also present in secondary lymphoid organs. They play an important physiological role in T cell homeostasis because they secrete survival cytokines such as IL-7. Additionally, we and others have demonstrated that they
A role for endocytic proteins in muscle mechanotransduction – EndoMechano
Autosomal dominant Centronuclear myopathy (CNM) is a rare neuromuscular disorder due to mutations in the DNM2 gene coding for Dynamin 2 (DNM2). We have demonstrated that the ubiquitous clathrin heavy chain (CHC) and DNM2, well characterized for their role in endocytosis of clathrin-coated vesicles,
From Heart development to Heart Regeneration – HeartCaRe
Cardiovascular diseases are the leading cause of mortality (33% of all deaths in the USA in 2008 and 29% in France). Cardiac diseases are characterized by molecular, cellular and physiological changes in the myocardium, coronary vessels and valves, resulting in cardiomyocyte deficiency and impaired
deFective Autophagie in Sinusoidal endothelial Cells In Non Alcoholic sTeatohEpatitis Development – FASCINATED
In this proposal, we hypothesize that a defect in autophagy in liver sinusoidal endothelial cells (LSEC) occurs in NASH and contributes to the development of this disease. 1. We analyzed by electron microscopy autophagic vacuoles in LSEC in patients with NASH, bland steatosis and in controls with ab
EXploration and modulation of TREM-1 in Atherosclerosis and Myocardial infarction – EXTREM
Human and animal studies have shown that innate immunity plays a major role in cardiovascular diseases. Monocytes/macrophages promote atherosclerotic plaque initiation, progression and rupture and participate to excessive cardiac remodelling following acute myocardial infarction (MI) through the pro
Role of dynamin 2 in muscle under normal and pathological conditions – Dynamuscle
Intracellular organization and transport is fundamental for the function of eukaryotic cells. Dynamins are a prototype class of mechano-enzymes and key regulators of membrane fission. These large GTPases regulate the scission of nascent vesicles from the plasma membrane during endocytosis; they also
Macrophage ontogeny and homeostasis in obesity and diabetes – FATMAC
1. Map the ontogeny and homeostasis of MF during metabolic stress. 2. Determine the specific role of proliferative MF in metabolic stress and T2D. 3. Assess the role of c-Jun in MF homeostasis during metabolic stress and T2D. 1. Map the ontogeny and homeostasis of MF during metabolic stress. Prog
The estrogen receptor (ER)alpha46, the “forgotten” isoform which emerges as the third estrogen receptor. – EmERgence46
Although estrogens, produced by ovaries, are key protective molecules in vascular, bone physiology and glucose metabolism, their proliferative actions on breast and uterus epithelium limit their long-term use at menopause. Estrogen receptor (ER) a but not ERß, mediates these effects and beside the w
Biomarkers of lipid status and metabolism in retinal ageing – BLISAR
Age-related macular degeneration (AMD) is responsible for 50 % of the cases of blindness in industrialized countries. It results from a pathological ageing of the retina, linked to a dysfunction of the retinal pigment epithelium (RPE), responsible for the recycling of the photoreceptors outer segmen
Targeting Renal Chloride Channels : A Novel Strategy to treat Hypertension – HYPERSCREEN
The molecular mechanisms underlying the pathogenesis of hypertension are still poorly understood. What is known is that excessive dietary salt represents a major risk factor for human hypertension, and it is clear that hypertension results from increased sodium absorption within the distal nephron o
Development, Microenvironment and genetic alterations in adrenal and bone lesions of Carney complex – DevMiCar
Carney complex (CNC) is a rare genetic disease responsible for bone tumors (osteochondromyxomas, OCM) and hypersecreting adrenal lesions (primary pigmented nodular adrenocortical disease, PPNAD) causing pituitary-independent Cushing's syndrome (hypercortisolism). PRKAR1A, the main gene mutated in CN