Department of Endocrinology, Metabolism and Diabetes (EMD)

Director:		Deputy-directors:
Agnès LEHUEN		Tarik ISSAD	Carina PRIP-BUUS

The EMD department is composed of 10 teams whose research topics aim at deciphering the role of membrane receptors and signal transduction pathways in tissue and body homeostasis according to developmental, nutritional, hormonal, and microenvironment cues, as well as their implications in physiological and pathological situations such as endocrine and metabolic disorders. This new department has been reinforced by the arrival of one renowned team from Saint-Vincent-de-Paul, the team  A  Lehuen & R Mallone.

This newly proposed Department will gather scientists with a solid background in both basic science and medical research, with strong clinical interactions within different complementary fields such as membrane receptor function, signaling pathways, metabolism and diabetes (including both immunological and metabolic aspects). Our ambition is that launching of these research programs will further increase our visibility and attractiveness and foster new interactions with clinical and industrial partners.

Teams

Genomics and signaling of endocrine tumors
Team leader: Jérôme BERTHERAT

Mitochondria, bioenergetics, metabolism and signaling
Team leader: Frédéric BOUILLAUD

Mucosal microbiota in chronic inflammatory diseases
Team leader: Benoit CHASSAING

Functional pharmacology and pathophysiology of membrane receptors
Team leader: Ralf JOCKERS

Immunology of Diabetes
Team leader: Agnès LEHUEN

T-cell tolerance, biomarkers and therapies in type 1 diabetes
Team leader: Roberto MALLONE & Sylvaine YOU

Receptor signaling and molecular scaffolds 
Team leader: Stefano MARULLO

Iron and immunity
Team leader: Carole PEYSSONNAUX

Insulin signaling, glucose sensing and glucotoxicity
Team leader: Catherine POSTIC & Tarik ISSAD

Functional pancratic beta cell mass in rodent and human
Team leader: Raphael SCHARFMANN

Physiopathology of AMPK and AMPK-related protein kinase in diabetes and obesity
Team leader: Benoit VIOLLET

1-Key topics

The main research of our Department deal with energy metabolism and its endocrine and immune control, to provide a better understanding of the pathophysiology of metabolic disorders (diabetes, metabolic syndrome…) and to develop new therapeutic strategies as well as innovative translational research tools. Several teams already have strong interactions with local on-site clinicians for translational applications.

The research projects of the EMD’s teams fall within several major axes:

• The analysis of signal transduction pathways downstream of hormonal, nutritional and developmental signals in various organs, with special emphasis on endocrine, metabolic and digestive organs.

• The study of the transcriptional responses controlled by these signaling pathways.

• The analysis of membrane receptors (including variants with impaired signaling properties) and downstream cellular responses such as proliferation, survival, differentiation, in both physiological and pathological situations.

• The exploration of metabolic pathways controlling energy and nutrient homeostasis and their deregulation during metabolic disorders such as obesity and diabetes.

• The genetic profiling of endocrine tumors.

• The development, destruction and regeneration of endocrine cells.

• The role of immune cells in both protection against and pathogenesis of diabetes.

2-Common scientific and technical interests

The projects conducted by all the teams of the department involve investigations at the molecular, cellular and physiological levels. They take advantage of the various core facilities (“platforms”) of the Institute. In addition, various teams of the department have developed a number of sophisticated technical approaches and molecular tools including:

- Real-time imaging, study of protein-protein interactions in living cells with Resonance Energy Transfer-based methods (BRET, FRET).
- In vivo bioluminescence imaging.
- Transcriptomic and proteomic approaches.
- Creation of tumor libraries in collaboration with on-site clinicians.
- Use of various genomic tools on large collections of clinical biological samples and next generation sequencing.

The Department benefit from an important number of mouse models generated by the different teams and the expertise in phenotyping specific traits of metabolic (glucose, fatty acid, insulin, iron, cAMP, Wnt/Betacat…), hypoxic (PHD-HIF), bioenergetic (AMPK, mitochondrial function, oxidative stress…) and immune pathways (innate and adaptive).

Fruitful interactions exist between teams of the department and teams belonging to the two other departments of the Institute (3I and DRC) and strategic interactions between departments for emerging research topics, such as « cancer and metabolism », are supported by various transversal clubs in the Institute.

3-International competitiveness

The EMD department is present in several research consortium programs, including LabEx (Gr-Ex, Who Am I, Inflamex, REVIVE) and DHU (Département Hospitalo-Universitaire, AUTHORS: autoimmune and hormonal diseases). Moreover, several teams in the department are involved in European projects, including a starting ERC grant. The activity of the EMD department further comprises translational approaches, which have led to fruitful interactions with pharmaceutical companies, to the establishment of industrial contracts and to start-up creation. The proposed reorganization of the EMD department, reinforced by the arrival of the clinical department of Diabetology (headed by Prof C. Boîtard) at the Cochin Hospital and the creation of the DHU, will further increase our international visibility and will reinforce collaborations among current and new teams.