CV Science

Agnès Conjard-Duplany PhD Human biology - HDR

Course and current status

1995: PhD (university Lyon 1, France): enzymatic activities in microdissected muscle fibers isolated from CRF and myopathic patients

1995-1998: Postdoctoral position (Constance, Germany):  Fiber type transition during muscle electrical stimulation.

1999-2005: Postdoctoral position (University Lyon1, France) : renal proximal tubule metabolism during starvation and acidosis

2006-2015: academic researcher, INSERM, Lyon 1: renal glucose metabolism in diabetes and toxicology

2011-2015: director of team EA4611, Lyon 1 University- Effects of antidiabetic drugs on renal and hepatic metabolism

2016-2020:academic researcher, INMG, U1217, Lyon1 - Role of mTOR protein in mouse muscle

Scientific summary

The mechanistic Target Of Rapamycin (mTOR) is an essential intracellular Ser-Thr kinase that regulates a vast range of molecular and cellular activities, including transcription, translation, ribosome biogenesis, autophagy, cell growth, angiogenesis, metabolism and actin cytoskeleton organization. 

The implication of muscle mTOR signaling downregulation in neuromuscular disorders, drug-induced myotoxicity, aging, together with the therapeutical targeting of mTOR underscore the importance of characterizing muscle mTOR targets and outcomes of muscle mTOR inhibition. Our general goal is the understanding of the pathophysiology of muscle mTOR signaling downregulation using specific genetic mouse models lacking muscle mTOR signaling that we have generated.

Our project will ultimately lead to strategies for muscle protection related to muscle mTOR inhibition, in addition to identify new biomarkers to monitor mTOR-mediated muscle disease progression for timely diagnosis and therapeutic options.

Previous work : Renal gluconeogenesis is stimulated in type 2 diabetic patients but the mechanisms responsible for such stimulation remains unknown. A marked stimulation of renal gluconeogenesis was observed in renal proximal tubules from diabetic ZDF rats with near-physiological concentrations of glutamine, lactate or glycerol. The stimluation was caused by an increase in the activities and mRNA levels of the key gluconeogenic enzymes. Experimental evidence suggests that glucocorticoids and cAMP were two factors responsible for the long-term stimulation of renal gluconeogenesis. 

For access to the complexity of the metabolism and all enzymatic pathways, C13 NMR spectroscopy is a tool that we longitudinally use, and whitch, coupled to enzymatic measurements already allowed us i) to identify disturbances in the metabolism of lactate by uranium and cadmium in human and murine proximal tubules ii) to highlight a lack of glucose synthesis from glutamine in rat intestine and iii) to confirm the key role of glutaminase to the provision of glutamate in brain.