Team 12: Molecular Pathophysiology of Adrenal & Endocrine Tissues

Adrenal tumorigenesis & adipose tissue homeostasis (team leader: A. Martinez, DR CNRS). Our team is interested in the pathophysiology of the adrenal cortex and adipose tissue. We focus on the molecular mechanisms involved in adrenal tumorigenesis and in the onset of obesity. Our team has expertise on the function and transcriptional control of enzymes of the aldose reductase family, in steroidogenic organs. 

Research

We develop two projects that rely on genetically engineered mice. One aims at understanding the role of aldose reductases in the regulation of adrenal steroidogenesis and adipose tissue homeostasis. The other explores the cell signaling pathways involved in adrenocortical tumorigenesis.

  1. With the help of our academic collaborators, we found that some human and murine isoforms of aldose reductases are involved in the biosynthesis of prostaglandins. Through the use of genetic models developed in house (knockout mice and cells), we demonstrated the involvement of this prostaglandin synthase activity in the stress response of the adrenal gland, the inhibition of adipogenesis and the resistance to diet-induced obesity. Current projects focus on adipose tissue and aim at understanding the importance of the different aldose reductase isoforms on adipocyte differentiation and metabolism in vitro and in vivo through gain-of-function models and human tissue specimens. These studies should bring to light new pathways influencing the onset of obesity.

  2. The goal of this project is to develop mouse models that allow the validation of adrenal tumorigenesis candidate genes initially identified in patients by our clinical collaborators of the COMETE and ENS@T networks. After devising the first mouse line allowing specific Cre-mediated gene recombination in the adrenal cortex, we used Cre/LoxP recombination to develop mouse models with targeted deregulation of the PKA and Wnt signaling pathways.  These demonstrated the importance of genes of the two pathways in triggering morbid hyperplasia, benign and malignant tumors of the adrenal cortex. We plan to combine these genetic abnormalities with deregulations of cell growth (IGF2, mTOR) or cell renewal (Hedgehog), in order to identify the molecular and cellular mechanisms responsible for tumor initiation and malignant transition. These models should provide a complete view of tumor progression and prove useful to evaluate new adrenal cancer therapies.

Research thematics

People

Last Name First Name Position Contact
Isabelle BARNOLA profile picture BARNOLA Isabelle Engineer
Marie BATISSE-LIGNIER profile picture BATISSE-LIGNIER Marie Clinician
Christelle DAMON-SOUBEYRAND profile picture DAMON-SOUBEYRAND Christelle Assistant Engineer
Cyril DJARI profile picture DJARI Cyril Ph.D Student
Typhanie DUMONTET profile picture DUMONTET Typhanie Ph.D Student
Anne-Marie LEFRANCOIS-MARTINEZ profile picture LEFRANCOIS-MARTINEZ Anne-Marie Professor
Marti LOPEZ SERRAT profile picture LOPEZ SERRAT Marti Research Technician
Antoine MARTINEZ profile picture MARTINEZ Antoine Principal Investigator
Mickael MATHIEU profile picture MATHIEU Mickael Ph.D Student
Jean-Christophe POINTUD profile picture POINTUD Jean-Christophe Associate Professor
Stephanie RODRIGUEZ profile picture RODRIGUEZ Stephanie Engineer
Amandine SEPTIER profile picture SEPTIER Amandine Research Engineer
Houda TABBAL profile picture TABBAL Houda Ph.D Student
Igor TAUVERON profile picture TAUVERON Igor Professor - Clinician
Pierre VAL profile picture VAL Pierre Senior Research Fellow

Publications