Biomedical research institute
Biomedical research institute
Team leader:
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Ralf Jockers |
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The team, directed by Ralf Jockers, including a group led by Julie Dam, is interested in understanding the function of membrane receptors in metabolic diseases. Membrane receptors are at the interface between the extracellular and intracellular environment and are thus crucial for cell communication. They respond to a wide variety of extracellular stimuli and are the targets of most of the drugs prescribed for human diseases. Hormonal activation of these receptors leads to the activation of intracellular signaling events. However, the adequate response may vary depending on the genetic background and the disease state of individuals. Our objective is to understand the dysfunction of membrane receptors in metabolic diseases like obesity and diabetes among others. Both diseases constitute major public health problems with 1.5 billion people being over-weight, more than 500 million people being obese and more than 350 million people having diabetes worldwide. There is therefore an urgent need for innovative therapeutic approaches. |
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We are interested in the investigation of the involvement of membrane receptors in metabolic diseases such as obesity and diabetes and its link to Alzheimer disease . We are particularly focusing our research on two membrane receptor families, the G protein-coupled receptor (GPCR) family and the cytokine receptor family to which the leptin receptor belongs. Among the various GPCRs studied the group has a major expertise on the melatonin receptor sub-family.
We are employing cutting-edge biochemical, pharmacological, endocrinological and proteomic approaches to understand the function of these receptors and evaluate their therapeutic potential by developing innovative techniques such as Bioluminescence Resonance Energy Transfer (BRET), Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) and enzyme complementation. These methods are complemented with knock-out and knock-in mouse models.
We are an international team of scientists coming from over ten different countries. Regular visiting PhD students, post-docs and senior scientists contribute to a highly cross-stimulating research environment. Established relationships with industrial partners allow the fast translation of our research results.
Karamitri A and Jockers R. Melatonin in type 2 diabetes and obesity. Nat Rev Endocrinol. 2018 Dec 7. doi: 10.1038/s41574-018-0130-1
Karamitri A, Plouffe B, Bonnefond A, Chen M, Gallion J, Guillaume JL, Hegron A, Boissel M, Canouil M, Langenberg C, Wareham NJ, Le Gouill C, Lukashova V, Lichtarge O, Froguel P, Bouvier M and Jockers R. Melatonin MT2 Receptor Variants Associated with Type 2 Diabetes Affect Specific Subsets of the Receptor Signaling Modalities. Science Signaling, 2018, 11(545). pii: eaan6622.
Institute news: A study directed by Ralf Jockers
INSERM Actualités du 02/10/2018
Wojciech S*, Ahmad R[FG1] *, Belaid-Choucair Z, Journé AS, Gallet S, Dam J, Daulat A, Ndiaye-Lobry D, Lahuna O, Karamitri A, Guillaume JL, Do Cruzeiro M, Guillonneau F, Saade A, Clément N, Courivaud T, Kaabi N, Tadagaki K, Delagrange P, Prévot V, Hermine O, Prunier C and Jockers R. The orphan GPR50 receptor promotes constitutive TGFβ receptor signaling and protects against cancer development. Nature Comm, 9:1216 (2018)
INSERM Actualités du 10/04/2018
Actualités scientifiques du CNRS 13/04/2018
Vauthier V*, Roujeau C*, Chen P, Sarkis S, Migrenne S, Hoisi T, Ozawa K, Rouille Y, Foretz M, Mallet J, Launay JM, Magnan C, Jockers R, Dam J. Endospanin 1 affects oppositely body weight regulation and glucose homeostasis by differentially regulating central leptin signaling. Mol Metabolism, 6(1):159-172 (2016).
Bonnefond A, Karamitri A, Jockers R, Froguel P. The Difficult Journey from Genome-wide Association Studies to Pathophysiology: The Melatonin Receptor 1B (MT2) Paradigm. Cell Metab. 2016 Sep 13;24(3):345 347
Baba K*, Benleulmi-Chaachoua A*, Journé AS, Kamal M, Guillaume JL, Dussaud S, Gbahou F, Yettou K, Liu C, Contreras-Alcantara S, Jockers R*, Tosini G*. Heteromeric MT1/MT2 Melatonin Receptors Modulate Photoreceptor Function. Science Signaling, Oct 8;6(296):ra89, (2013)..
Comment in: « Editor’s Choice » Science, 342 :535 (2013)
Bonnefond A*, Clement N*, Fawcett K, Yengo L, Vaillant E, Guillaume JL, Dechaume A, Payne F, Roussel R, Czernichow S, Hercberg S, Hadjadj S, Balkau B, Marre M, Lantieri O, Langenberg C, Bouatia-Naji N, MAGIC, Charpentier G, Vaxillaire M, Rocheleau G, Wareham NJ, Sladek R, McCarthy MI, Dina C, Barroso I, Jockers R* & Froguel P*. Rare MTNR1B variants impairing melatonin MT2 receptor function contribute to type 2 diabetes. Nat Genetics, 44:297-301 (2012)
Press release : Highlight in « Faits scientifiques 2012 » of Inserm.
(* equal contributions)
Melatonin and type 2 diabetes - the link becomes clearer
Linking melatonin receptor variants to signal differences leads to potential new therapeutics of type 2 diabetes
https://www.institutcochin.fr/institute/news/melatonin-and-type-2-diabetes-the-link-becomes-clearer?set_language=en
A new duo for the protection of breast cancer: the heterodimer complex GRP50 – TβRI
Free access article in Nat Comm (2018) 9:1216
Synthesis and characterization of first cell-impermeant and biased melatonin receptor ligands demonstrating functional expression of MT1 receptors in mitochondria
https://vimeo.com/221003747); YouTube
Free access article in Br J Pharmacol 2017 174:2409-21 and Proc Natl Acad Sci U S A (2017) E7997-E8006
Latest reference review on melatonin receptors: Update on melatonin receptors: IUPHAR Review 20
Free access article in Br J Pharmacol (2016) 173:2702-25
2019 Lab retreat
some photos, other photos......and more
2019 The team obtained for the 3rd time the label of Fondation pour la Recherche Médicale (FRM)
https://www.institutcochin.fr/institute/news/label-frm-team?set_language=en
2017 Marie Sklodowska-Curie Actions Seal of Excellence awarded to Atsuro Oishi and our team
2016 Best poster price for research engineers (INTERCHIM price) awarded to Marine Luka at the GDR-3545 meeting in Tours
2015 Price of the Fondation Philippe Chatrier awarded to Erika Cecon
The team obtained the label of Fondation pour la Recherche Médicale (FRM)- 2013[FG1]
Julie Dam, Laureate of the ANR Young Investigator program 2012
Member of the Labex «Who am I ?». Who am I? is a large, cooperative and multi-disciplinary research project focusing on the fundamental question of the origin of identity (http://www.labex-whoami.fr/en/who-am-i)
Member of the DHU (Département Hospitalo-Universitaire) AUTHORS « Autoimmune and hormonal diseases »
Direction of the Groupement de Recherche GDR-3545 “RCPG-Physio-Med”. The GDR-3545 on “G Protein-coupled Receptors : from physiology to drugs (RCPG-Physio-Med)” was created in 2012 by the CNRS
2018 Running to support type1 diabetes
2016/17 Several golf competition organized by Chatrier Fondation to support Alzheimer research
2016 ODYSSÉA PARIS 2016 to support cancer research
Video production of article abstract of the team (Gbahou, Cecon et al. Br J Pharmacol, 2017) https://vimeo.com/221003747); YouTube (https://bcove.video/2t7ukwc)
Photo shooting for France Alzheimer, May 2017 (1-2 example of the published photos?)
Interview Journal Science & Avenir, « A chinese plant against obesity», July, 2015
Participation in the “Nutrition Métabolisme » event organized on the occasion of the 50th anniversary of INSERM and "Les Chercheurs accueillent les Malades" (October 3rd, 2014).
Participation in the visit of the« Conseil de surveillance » of the Fondation pour la Recherche Médicale (September, 2014).
Interview for « HORIZON » Magazine of the European Commission on « Obesity genes reveal why we eat too much « (J. Dam, R Jockers, EurOCHIP consortium Partner) (August, 2014). https://cordis.europa.eu/project/rcn/92511_en.html
Pint of Science (J. Dam, R Jockers,(May 2014)
Visiting PhD students:
2013 Erika CECON (Brazil)
2015 Sharon OWINO (USA)
2017 Francesca PIAGGIO (Italy)
2018 Ana DUARTE NOSEDA (Brazil)
Visiting post-docs:
2015 Min PARK (Singapore)
2016 Atsuro OISHI (Japan)
Visiting professors:
2016 Gianluca TOSINI (USA) “Who Am I” Labex visiting professor
2018 Toru HOSOI (Japan)
Fondation pour la Recherche Médicale
Fondation Philippe Chatrier
International diabetes federation
Networks:
GDR-3545
Laboratory of Excellence "Who Am I?"
Départements Hospitalo Universitaires (DHU) https://www.b2match.eu/system/dhudays/files/p12.pdf?1476370652
Pharmacological targets (IUPHAR)
GPCR database(GPCRdb)
Protein data bank(PDB)
List of places / restau / co-working / leisure activities we “tested” in our 2017 lab retreats
Escape Game Bordeaux
Chateau Haut Brion
Co-working space Paris Cosy-corner
Co-working space Bordeaux WIGI
Co-working space Bordeaux Le Burro des Possibles (also good option for lunch!)
