Our team associates physiologists, cell biologists and clinicians devoted to find new targets and new biomarkers in osteoarthritis, particularly by exploring the role of metabolic diseases, mechanical stress and bone/cartilage/synovial tissue interactions.

Our team has been interested for several years in the objective to discover innovative treatments and  biomarkers in osteoarthritis (OA). We have developed several tools, from cell cultures to human cohort, from preclinical murine models to joint tissue analysis. Our projects are focused on the relations between OA and metabolic diseases:

• Role of innate immunity in OA
• Role of chondrocyte differentiation on bone angiogenesis
• Role of the cholinergic system in OA
• Role of adipose tissues in OA

 Pr Francis BERENBAUM
Contact : francis.berenbaum@aphp.fr
https://www.crsa.fr/equipe-francis-berenbaum.html

Cystic fibrosis physiopathology and phenogenomics

Our team develops projects related to cystic fibrosis (CF). We coordinate the national research study on modifier genes in which nearly 5,000 patients are participating. We have shown genes associated with the severity of several CF disorders as well as drug response, and characterize them functionally. We have developed a therapeutic molecule that modulates chloride efflux, and are analyzing its effects in vitro and in vivo prior to clinical application. We are analyzing various parameters associated with the exacerbated inflammatory response, in particular miRNAs. We study the infectious response to different pathogens, Pseudomonas aeruginosa, Staphylococcus aureus and Aspergillus fumigatus in particular, in order to understand the processes involved in the chronicisation of infections in CF patients.  We examine the role of antimicrobial peptides in the innate defense against these infections and their potential therapeutic application.

Pr Harriet CORVOL
Contact : harriet.corvol@aphp.fr
https://www.crsa.fr/equipe-harriet-corvol.html

Immune system and neuro-inflammation

Accumulating evidence support a key instrumental involvement of brain innate neuroinflammation and peripheral immunity in neurodegenerative diseases and other neurological disorders. Our studies aim at addressing the role of recently emerging aspects of innate and adaptive neuroimmune interactions in the pathophysiology of Alzheimer’s disease and Tauopathies, as well as other neuroinflammatory and/or neurovascular conditions (cerebral amyloid angiopathy, stroke, epilepsy). Our research strategy is based on a translational approach combining pre-clinical studies in transgenic mouse models, together with transversal and longitudinal clinical studies. We aim at developing innovative disease-modifying immunotherapy approaches and new blood-based immune biomarkers in such pathologies.

Dr Guillaume DOROTHEE
Contact : guillaume.dorothee@inserm.fr
https://www.crsa.fr/equipe-guillaume-dorothe-e.html

Lipodystrophies, metabolic and hormonal adaptations, and aging

Our team works on the pathophysiological mechanisms of lipodystrophies either of genetic, or acquired origin (during HIV infection or chronic glucocorticoid treatment), and on the related reproductive disorders.

Lipodystrophic syndromes are characterized by a defect in adipose tissue distribution and function, with potential metabolic, cardiovascular, and reproductive consequences. Thanks to in vivo (animal models, patient cohorts) and in vitro models we aim to: (i) understand the clinical and pathophysiological links between lipodystrophies, insulin resistance, adipose tissue aging, cardio-metabolic complications, and reproductive disorders; (ii) identify new therapeutic tools.

Pr Bruno FEVE
Contact : bruno.feve@inserm.fr
https://www.crsa.fr/equipe-bruno-feve.html

Neuroendocrine mechanisms of longevity and age-related diseases

This lab published groundbreaking work on insulin-like growth factors (IGFs) and aging, and is now focused on somatotropic signaling in longevity, regeneration and Alzheimer disease (AD). We showed that suppression of IGF-1R in stem cells enhances neurogenesis in the aging brain. We revealed that adult mice with ubiquitous disruption of IGF signaling are lean with resilient energy metabolism, creating an exciting new model for studying somatotropins in aging. We showed that blocking IGF signaling in neurons alleviates AD, identifying IGF-1R as a promising target for preventing neurodegeneration. To learn more about IGFs in health and longevity, we are investigating cellular and molecular mechanisms of IGF signaling in AD, and studying the role of IGFs in cellular homeostasis during aging.

Dr Martin HOLZENBERGER
Contact : martin.holzenberger@inserm.fr
https://www.crsa.fr/equipe-martin-holzenberger.html

Metabolic and biliary fibro-inflammatory diseases of the liver

Our research is dedicated to liver diseases, focusing on cholangiopathies. We investigate genetic deficiencies in the ABCB4 phosphatidyl-choline transporter, responsible for hereditary biliary diseases, the mechanisms of cell death that promote liver inflammation and fibrosis, and the sub-populations of liver myofibroblasts implicated in liver fibrosis and cholangiocarcinoma stroma. We combine cohort and experimental studies as well as clinical trials, to develop therapeutic innovations in these rare diseases and more frequent liver diseases including NAFLD and viral hepatitis B. Strategies combining serum tests, elastometry and magnetic resonance imaging, are also designed to develop predictive tests in liver diseases, which altogether represent a major health burden worldwide.

Pr Chantal HOUSSET
Contact : chantal.housset@inserm.fr
https://www.crsa.fr/equipe-chantal-housset.html

IGF system and foetal and postnatal growth

Fetal and post-natal growth is under the control of genetic, epigenetic and environmental factors. We are studying the pathophysiology of fetal growth linked to imprinted diseases in patients born small for gestational age or with excessive growth. In mice we are studying the mechanisms involved in the programming of growth and cardio-metabolic pathologies when perinatal nutrition is modified.

Our objectives are to improve the early detection of fetal growth abnormalities and childhood tumors and to understand the regulation of growth and metabolism, in order to propose new treatment strategies aimed at improving fetal growth, metabolism and tumor prognosis.

Pr Irène NETCHINE
Contact : irene.netchine@aphp.fr
https://www.crsa.fr/equipe-irene-netchine.html

Microbiota, gut and inflammation

Our main goal is to decipher the mechanisms underlying host-microbiota interactions in health and disease, particularly inflammatory bowel diseases. Our projects are based on complementary expertise, such as gastroenterology, intestinal microbiota ecology, intestinal epithelial cells physiology, analysis of hydrophobic molecules in the intestinal environment and host-microbe immune interactions. These skills, at the frontier of cell biology, immunology, microbiology and medicine, allow us to conduct extensive studies from bedside to bench and back again.

Pr Philippe SEKSIK & Pr Harry SOKOL
Contacts : philippe.seksik@aphp.fr / harry.sokol@aphp.fr
https://www.crsa.fr/equipe-philippe-seksik.html