Date of birth: 24/05/1956
Professional address: Institute of Developmental Biology and Cancer. UMR 6543 CNRS-University of Nice Sophia Antipolis. Faculty of Medicine, 06034 Nice, France
Leader of the group "Stem cells and Differentiation".
Education: Ph D in Molecular Biology (1984, University of Montpellier, France).
Post-doctoral stay (1992-1994): Institute for Stem Cell Research (Pr. Austin Smith, University of Edinburgh, UK).
Editorial Board: Member of the Editorial Board of the “Stem Cells” journal, of the "American Journal of Stem Cells" journal and « Editorial Advisor » for Biochemical Journal.
Committee: Membre of ARC National committee (CN3).
2005 “Stem cells from Human adipose tissue (hMADS cells)”. French patent n° 0209799. Inventors : Anne-Marie Rodriguez, Christian Dani, Gérard Ailhaud. Co-owners: CNRS and Yves Saint Laurent Beauté
2007- « Stem cells from human adipose tissue and derived differentiated cells» PCT : USA (n° 10/6352581) ; Japan (n°2004-525 503) ; Canada (n°2493532); Australia (n°2003278212); Brazil (n°PI0305721-6); Europe (n°03766432.3). Inventors : Rodriguez, Dani, Ailhaud. Co-owners : CNRS et Yves Saint Laurent Beauté. With licence.
2009- “Established Human Brown adipocyte line and method for differentiation from hMADS cell line” French patent N° 0854140 with a PCT extension on 23rd June 2009, PCT/EP2009/057852. Inventors: Ailhaud, G, Dani, C, Elabd, C & Amri, EZ. Owner: CNRS. With licence.
2010: “Composition inducing or up-regulating UCP1 for use in treating of preventing overweight, adiposity, obesity, metabolic syndrome or related diseases or disorders” European patent office: application number EP10162363, May 7. 2010: French/Austrian joined patent. Inventors: Ailhaud, G, Dani, C, Amri, EZ, Karbiener, Co-owners: CNRS and University of Graz (Austria)
2011: « A pharmacological compound to eradicate cancer stem cells”. The CNRS (FIST) agreed in July 2010 to fill a patent to protect this invention (DI 03910-01). Inventors: Darini, C, Dani, C, Drici, M, Ladoux, A. Owner: CNRS
The main goals of our activity is to refine our knowledge of the biology of stem cells in adipose tissues and skeletal muscles.
A pool of adipocyte progenitors remains present in adipose tissue during adult life. This pool is responsible for the renewal of adipocytes and the potential of this tissue to expand in response to chronic energy overload. Adipocyte progenitors are also present in healthy skeletal muscle, and undergo adipocyte differentiation in muscular dystrophy diseases. However, factors controlling proliferation and differentiation of human adipocyte progenitors are largely unknown.
To investigate this field we have established mesenchymal stem cells derived from human adipose tissue, termed (hMADS) cells: i) FGF2, activin A, Hedgehog, oxytocinand miR30 have been identified as key regulators of hMADS cell proliferation and differentiation ii) we have characterized signalling pathways mediating FGF2 and activin A effects, iii) we have proposed a model in which factors secreted by macrophages located in obese adipose tissues regulate adipose progenitor self-renewal.
The developmental origin of adipocyte progenitors has been largely disregarded until now. Observations emerging from adipocyte differentiation of mouse embryonic stem cells and from in vivo lineage tracing studies, led us to reveal a different origin for cephalic and truncal adipocytes in mouse.
Finally, we have reported the potential of white adipocytes to turn into brown adipocytes.
- To address the developmental origins of adipocytes in humans. For that purpose we have generated induced Pluripotent Stem cells and we are developing their differentiation into adipocytes as a novel model to investigate the earliest events of human adipocyte differentiation. As it is established that adipocyte progenitors have different intrinsic properties depending on their body location and that their differentiated progenies have different impact on metabolic disorders, our project is to address the importance of developmental origins of adipocyte progenitors with respect to the functional properties of adipocytes.
- To identify regulators of human adipose progenitor self-renewal. We will study the role of hypoxia and of Hedgehog pathways. Preliminary experiments suggest that miRNAs and factors secreted by macrophages play a critical role in the commitment of adipocyte progenitors into adipogenesis. We will investigate the role of these factors in more details.
- To investigate the role of adipocyte progenitors in human skeletal muscle and to study factors involved in their proliferation and differentiation in muscular dystrophy diseases and atrophied muscles (bedrest and microgravity). All together the expected results will provide a characterization of the muscle adipocyte progenitors, regarding their specificity, their lineage, and their role in normal and pathological situations. Their possible interactions with the myogenic progenitors may be a new important aspect to consider for muscle disorder therapies.
In an obesity and muscular diseases context, comprehension of the origins of adipocyte progenitors, mechanisms regulating their self-renewal, differentiation and plasticity may help to identify the pathways responsible for pathological adipose tissue expansion and/or the associated metabolic disorders.