Delphine Duteil, Inserm scientist in steroid hormon receptors in skeletal muscle

Firstly, during her thesis, her research work focused on the study of the role of different nuclear receptors and their co-regulators in skeletal muscle. In particular, she highlighted that glucocorticoid (GR), androgen (AR) and peroxisome proliferator receptors (PPARb) affect muscle mass and strength, but also the type of fibers that make up the muscle. These receptors may interact with p160 family co-regulators in the control of obesity and type 2 diabetes.

Delphine was then interested in epigenetic modifications, which correspond to changes in gene activity, not involving changes in the DNA sequence but in the proteins around which the DNA is wrapped, the histones. She focused on LSD1, a histone demethylase found in most tissues including muscle and fat. She found that LSD1 does not interact with the same transcription factor depending on the cell type, and that LSD1 may be involved in :

• thermal regulation ;
• fat storage ;
• fatty acid and carbohydrate oxidation.

Currently, she is focusing on the action of glucocorticoids and androgens in muscles. In particular, Delphine is interested in what happens at the molecular level. She has been involved in demonstrating that :

• The glucocorticoid receptor collaborates with MYOD1 to regulate the expression of genes involved in the anti-anabolic pathway, which blocks protein production in muscle fibers.
• The androgen receptor plays a major role in the regulation of metabolism, amino acids, sugars and lipids.

The scientist intends to detail the molecular mechanisms underlying these processes. In collaboration with Isabelle Billas' team, Delphine is also studying the structure of the binding domains of the glucocorticoid receptor when it is bound to a target DNA fragment.

The Habilitation to direct research, obtained by Delphine, also formalizes her involvement in the co-supervision of a PhD student, Kamar Ghaibour, who works on the effect of androgens in skeletal muscle regeneration.

Légende: Organization chart describing the group led by Delphine Duteil as well as the themes that make up her current research topic.

The research project that she now wishes to develop, with the help of Dr. Qingshuang Cai, concerns the modulation of nuclear receptor activity by influencing that of their co-regulators. In particular, Delphine is interested in the co-regulator LSD1 and its effect on muscle atrophy induced by glucocorticoids. At present, long-term glucocorticoid treatments cause harmful side effects for the patient, including muscle atrophy. In order to reduce these side effects, a possible approach would be to target the co-regulators of the glucocorticoid receptor. This research project led by Delphine could then lead to new treatment approaches to mitigate these adverse effects.