CV Science

Céline Luquain-Costaz PhD Biochemistry

Course and current status

Associate Professor - Biochemistry

Department of BioSciences
INSA-Lyon, 20 Av. Albert Einstein,
F-69621 Villeurbanne, France

 http://biosciences.insa-lyon.fr/

Principal Investigator - Atherosclerosis, Lipoproteins, Macrophages & Cholesterol 

Cardiovascular, Metabolism, diabetology and Nutrition
CarMEN Institute INSERM UMR1060
Bldg IMBL, INSA-Lyon, 20 Av. Albert Einstein,
F-69621 Villeurbanne, France

http://carmen.univ-lyon1.fr/

Team 4: INgenierie and FOnction of LIpids and lipoProteins (INFOLIP)

 Position

• Sept. 2007-now: Associate Professor, Department of BioSciences, National Institute of Applied Sciences Lyon (INSA-Lyon). Research topics: Cardiovascular, Metabolism, diabetology and Nutrition  Research interest: Intracellular trafficking of cholesterol in macrophages

• 2006-2007: Postdoctoral fellow – Institute of protein biology and chemistry, CNRS UMR 5086, Lyon. Team « oncogenesis et apoptosis » (Pr. G. Gillet). Development of a new anti-ischemic therapy targeting the death protein Bid.
  
• 2003-2006 : Postdoctoral fellow – Laboratory of Genetic and cancer, CNRS UMR 5201, Lyon. Team « Rafts et cellular signaling » (Dr S Manié). Characterization of a lipid rafts resident protein, Pdro, involved in intracellular trafficking of cholesterol
• 2001-2003 : Postdoctoral fellow – Department of cellular and developmental biology. Team « Lipid mediators and cancer » (Dr. Andrew Morris), The university of North Carolina at Chapell Hill, USA. Metabolism of lysophosphatidic acid, an ovarian cancer biomarker. 

Educational background

• 1997-2000: PhD in Biochemistry. Laboratory of Biochemistry and pharmacology National Institute of Applied Sciences Lyon INSA-Lyon, INSERM U352, Villeurbanne. Supervisor: Pr. C Laugier. Structural and metabolic analysis of Bis(monoacylglycero)phosphate in rat uterine stromal cells.
• 1996-1997: Master degree in Biochemistry (INSA-Lyon) Laboratory of Biochemistry and pharmacology INSA de Lyon, INSERM U352, Villeurbanne. Supervisor: Pr. Christian Laugier.

Teaching skills

• Analytical Biochemistry
• Structural and dynamic Biochemistry
• Enzymology

Scientific summary

Cardiovascular diseases (CVD) are the leading cause of death in developed countries. One of the most common causes of CVD is atherosclerosis, which is defined as a chronic inflammatory disease associated with lipid metabolism disorders. This results in a gradual occlusion of the vessel lumen due to the formation of a so-called atheromatous plaque, in a complex and dynamic process called atherogenesis. This processus is increased in diseases associated with high oxidative stress as the metabolic syndrome and type 2 diabetes. Atherosclerotic plaque in the arterial wall is due to the accumulation of fibrous tissue and various substances, including lipid deposits represented by cholesterol engorged macrophages, also called "foam macrophages."

These macrophages play an important role in atherogenesis related to disregulation of cholesterol homeostasis. Most of cell cholesterol derived from the endocytosis of low density lipoprotein (LDL). After internalization, LDL reach early and late endosomes. The majority of the free cholesterol is then distributed to the plasma membrane where it is incorporated or effluxed by extracellular acceptors as HDL or ApoA1. Many questions still persist on intracellular transport pathways of cholesterol especially from late endosomes and the molecular mechanisms involved.

In this context, I am interested in a specific phospholipid resident of late endosomes, the Bis (Monoacylglycero) phosphate (BMP), largely involved in the regulation of cholesterol homeostasis in interaction with plasma lipoproteins (Delton-Vandenbroucke, 2007 ). More recently, we have shown that the cellular accumulation of BMP disrupts the cellular distribution of LDL-derived cholesterol thus inducing changes in the activity / expression of LXR and ABCA1 transporters and G1 and, ultimately, reducing the cholesterol efflux stimulated by HDL. (Luquain-Costaz, 2013). BMP also exercises protective effects against cell death induced by oxidized LDL via a decrease in the cellular production of pro-apoptotic oxysterols (Arnal-Levron, 2013).

Ongoing studies aim to describe the mechanisms involved, focusing on oxysterols binding proteins (OSBP and related proteins ORP), to confirm the regulatory role of BMP in the functionality of lipoproteins isolated from diabetic patients.