Functional Pharmacology and Pathophysiology of Membrane Receptors

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 therefore crucial for cellular communication and biological response. Our objective is to understand the dysfunction of membrane receptors in metabolic diseases like obesity and diabetes and its link to Alzheimer disease. These 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.
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 the investigation of knock-out and knock-in mouse models.
We are an international team of scientists coming from coming from all over the world.  Established relationships with industrial partners allow the fast translation of our research results.

5 Main publications of the team in the last 5 years

1. Leptin brain entry via a tanycytic LepR-EGFR shuttle controls lipid metabolism and pancreas function. Duquenne M, Folgueira C, Bourouh C, Millet M, Silva A, Clasadonte J, Imbernon M, Fernandois D, Martinez-Corral I, Kusumakshi S, Caron E, Rasika S, Deliglia E, Jouy N, Oishi A, Mazzone M, Trinquet E, Tavernier J, Kim YB, Ory S, Jockers R, Schwaninger M, Boehm U, Nogueiras R, Annicotte JS, Gasman S*, Dam J*, Prévot V*. Nat Metab 2021

Aug; 3(8):1071-1090. doi: 10.1038/s42255-021-00432-5. Epub 2021 Aug 2. PMID: 34341568

2. SARS-COV-2 spike binding to ACE2 in living cells monitored by TR-FRET. Cecon E, Burridge M, Cao L, Carter L, Ravichandran R, Dam J*, Jockers R*. Cell Chem Biol 2022 Jan 20;29(1):74-83.e4. doi: 10.1016/j.chembiol.2021.06.008. Epub 2021 Jul 2. PMID: 34246414

3. Novel repertoire of tau biosensors to monitor pathological tau transformation and seeding activity in living cells. Cecon E, Oishi A, Luka M, Ndiaye-Lobry D, François A, Lescuyer M, Panayi F, Dam J, Machado P, Jockers R. Elife 2023 Mar 14;12:e78360. doi: 10.7554/eLife.78360. PMID: 36917493

4. Mitochondria-targeted melatonin photorelease supports the presence of melatonin MT1 receptors in mitochondria inhibiting respiration. Somalo-Barranco G, Pagano Zottola AC, Abdulrahman AO, El Zein RM, Cannich A, Muñoz L, Serra C, Oishi A, Marsicano G, Masri B, Bellocchio L, Llebaria A, Jockers R. Cell Chem Biol 2023 Aug 17;30(8):920-932.e7. doi: 10.1016/j.chembiol.2023.07.009. PMID: 37572668

5. Human GLP1R variants affecting GLP1R cell surface expression are associated with impaired glucose control and increased adiposity. Gao W, Liu L, Huh E, Gbahou F, Cecon E, Oshima M, Houzé L, Katsonis P, Hegron A, Fan Z, Hou G, Charpentier G, Boissel M, Derhourhi M, Marre M, Balkau B, Froguel P, Scharfmann R, Lichtarge O, Dam J, Bonnefond A, Liu J, Jockers R. Nat Metab 2023 Sep 14. doi: 10.1038/s42255-023-00889-6.


Ralf Jockers

Institut Cochin, 22 rue Méchain, 75014 Paris

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