Dominique DETAILLE Born on september 17th, 1969
E-mail: [email protected] or [email protected]PhD in Biology Project: Scientific collaborator in a public or private research laboratory on Biomedical topics. Education 2002 - Ph.D. in Biology (Adviser: Professor Pierre Devos)
Title: The Xenopus laevis oocyte as experimental tool for the study of an antidiabetic drug, metformin, controlling insulin-regulated glucose metabolism.
1993 - License (master degree) in Biochemical Sciences
University of Liège, Walloon Center for Industrial Biology (CWBI), Belgium Title: Study of xenobiotic compounds degradation pathways by microorganisms. 1 communication
1991 - License (master degree) in Zoological Sciences
University of Namur (FUNDP), Belgium Faculty of Biological Sciences Title: Fructose 2,6-bisphosphate and bioamines as regulators of ion transport in isolated gills of the Chinese crab, Eriocheir sinensis, acclimated to fresh water. 1 publication
Professional experience # 04/2007 – End 2008: Associate Researcher at the University of Salamanca, Spain
Scientific collaborator on various projects: (Advisers: Professors Yehia El-Mir and J.M. Lopez-Novoa)
a) Metformin and gentamicin-induced nephrotoxicity: in vivo studies. b) Silibinin and hepatic mitochondrial metabolism in nutritional models of insulinoresistance/oxidative stress (Funded by Ministerio de Educación y Cienca) c) Direct hepatic effects of glitazones in monotherapy or combination with metformin (Funded by Ministerio de Salud y Consumo/Fondo de Investigación Sanitaria) 1 publication, 3 abstracts published Supervision of students in thesis, new experiments planning
# 08/2002 – 03/2007: Post-Doc researcher at the Joseph Fourier University of Grenoble, France
Project: (Adviser: Professor Xavier Leverve)
Metformin and derivatives in the control of oxidative stress-induced cell death (Funded by the pharmaceutical industry Merck-Santé, Lyon, France) 8 publications, 2 oral communications, 5 abstracts (3 published)
Team working in LBFA, Unit INSERM (U884) with multiple partnerships and international collaborations Workshop co-animation (Fête de la Science, 24-25/10/05), regular apprenticeship of technology to trainees
# 05/1998 – 07/2002: Doctoral researcher at the University of Namur. Fellowship from pharmaceutical industry Merck-Santé (Lyon, France) Research Unit in Biology of the Organisms (URBO) - Comparative Biochemistry and Physiology # 06/1995 – 04/1998: Research scientist at the University of Namur in convention with the pharmaceutical group Merck-Lipha: Identification of cellular and molecular mechanisms by which metformin enhances insulin- dependent glucose metabolism in Xenopus laevis oocytes 1 publication, 3 abstracts (2 published) # 03/1994 – 06/1994:Research scientist at the University of Namur in convention with the Walloon Region and the University of Liège: Study of hormonal factors similar to crustacean prolactins and somatotropic hormone Languages and Computer skills
- French (mother tongue) - English (good level) - Dutch (school level) - Spanish (basic notions, improvement in progress) - Processing Data tools:
Cricket Graph, Photoshop, Color It, Graphic Convertor, ImageJ: occasional use
Technical and scientific skills Experimental techniques in physiology: Measurement of intracellular inorganic ions concentrations by spectro-metry; use of osmometer; perfusion of crustacean gills; microinjection of substances bioactive (proteins, drugs, nucleic acids) into Xenopus laevis oocytes; use of radioisotopes (14C, 32P, 3H, 125I); isolation of mitochondria from liver and kidney tissues; preparation of isolated rat hepatocytes by collagenase digestion (basal use); direct measurement of oxygen consumption rate by oxygraphy; investigation of the mitochondrial permeability transition pore regulation, i.e. calcium retention capacity, upon digitonin-permeabilized cells; measurement of reactive oxygen species production on both intact or permeabilized cells, and isolated mitochondria.
Experimental techniques in biochemistry: subcellular fractionation and sucrose gradient; SDS-PAGE in one dimension (silver and Coomassie blue stainings); autoradiography of labelled proteins; RIA; Western Blot analysis (determination by colorimetric and chemiluminescence methods); chromatography HPLC (separation of nucleotides); synthesis of transcripts from cDNA; spectrofluorimetry; protein assays (Biuret, Bradford, Lowry, Pierce).
Cell/bacteria culture: microorganisms (bacteria strains: Pseudomonas, Arthrobacter, Bacillus) cultures in flasks and small fermentors; immortalized cell lines (KB, HMEC-1, U937, K562, C6, HL-1, Caco-2) and primary cell (BAEC, HUVEC, neurons) cultures; cellular death determination by various methods (blue trypan exclusion test, annexin V-propidium iodide double staining and subsequent analysis by flow cytometry).
Microscopy: optical, phase contrast, classical fluorescence and confocal; immunocytochemistry; mitochondria staining by autofluorescence (NADH, FAD) or by use of different exogenous probes (TMRM, mitotracker, calcein/cobalt, mitoSOX, DCF-DA).
Animal handling: use of fasted/starved Wistar rats (subcutaneous injection of antidiabetic drugs or supplementation in drinking water, animals anesthetized with an i.p.injection of pentobarbital for hepatocytes isolation).
Other acquired skills: scientific writing and oral presentation in english (list of publications, congresses, and workshops annexed), projects and reports writing in English, reviewing of manuscripts.
Miscellaneous
- 2 memberships: Groupe Français de Bioénergétique (GFB) since 2003; Société Belge de Biochimie et de Biologie Moléculaire (SBBBM) since 1993
- Various trainings in molecular biology, geology, marine biology and fresh water ecology
APPENDIX – Scientific writing and presentations Events: congresses, workshop, symposium
- First European Forum of Young Scientists, Liège, Belgium (July, 1993) - 155th meeting of the Belgian Society of Biochemistry and Molecular Biology, SBBBM (Topic: molecular mechanism of tumor rejection) in Woluwé, Belgium (November 20, 1993) - 161th meeting of the SBBBM (Topic: Signal transduction and disease) in Brussels, Belgium (25 november 1995) - Annual meeting of the Royal Society of Chemistry (Topic: Structure and biology of receptors. Role in design of new drugs), Brussels, Belgium (June 3-4, 1996) - "Protein phosphorylation in signal transduction pathways" symposium, Leuven (04/10/1996) - 3th Benelux Congress of Zoology, Namur, Belgium (November 8-9, 1996) - 165th meeting of the Belgian Society of Biochemistry and Molecular Biology (Topic: Glucose transport and metabolism), Jette, Belgium (March 8, 1997) - 16th International Diabetes Federation (IDF) Congress, Helsinki, Finland (July 20-25, 1997) - Workshop (Topic: Control of metabolism and insulin action) organized by the European Association for the Study of Diabetes (EASD), Geneva, Switzerland (October 9-11, 1997) - 30th annual meeting of the Endocrine Pancreas contact group, Brussels (13/12/1997) - 34th EASD meeting, Barcelona, Spain (September 8-12, 1998) - Research in Biology Conference, Namur, Belgium (October 8, 1998) - 35th EASD meeting, Brussels, Belgium (September 29 - October 2, 1999) - Doctorate School, Namur, Belgium (January, 2001) - 12th EBEC congress, Arcachon, France (September 10-15, 2002) - 18th IDF Congress, Paris, France (August 24-29, 2003) - 3th French Bioenergetics Group(GFB) congress, Aussois, France (September 26-29, 2003) - Research in Biology Conference, Grenoble, France (November 13, 2003)
Publications, oral communications and posters - Papers -
- Detaille D., Trausch G. and Devos P. (1992) Dopamine as a modulator of ionic transport and glycolytic fluxes in the gills of the Chinese crab, Eriocheir sinensis. Comp. Biochem. Physiol. 103C, 521-526
- Detaille D., Wiernsperger N. and Devos P. (1998) Potentiating effect of metformin on insulin-induced glucose uptake and glycogen metabolism within Xenopus oocytes. Diabetologia 41, 2-8
- Detaille D., Wiernsperger N. and Devos P. (1999). Cellular and molecular mechanisms involved in insulin's potentiation of glycogen synthase activity by metformin. Biochem. Pharmacol. 58, 1475-1486
- Detaille D., Wiernsperger N. and Devos P. (1999). Metformin interaction with insulin-regulated glucose uptake, using the Xenopus laevis oocyte model expressing the mammalian transporter GLUT4. Eur. J. Pharmacol. 377, 127-136
- Detaille D., Guigas B., Leverve X.M., Wiernsperger N. and Devos P. (2002) Obligatory role of membrane events in the regulatory effect of metformin on the respiratory chain function. Biochem. Pharmacol. 63, 1259- 1272
- Leverve X.M., Guigas B., Detaille D., Batandier C., Koceir E.A., Chauvin C., Fontaine E. and Wiernsperger N. (2003). Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Diabetes Metab. 29, 88-94.
- Guigas B., Detaille D., Chauvin C., Batandier C., De Oliveira F., Fontaine E. and Leverve X. (2004). Metformin inhibits mitochondrial permeability transition and cell death: a pharmacological in vitro study. Biochem. J. 382, 877-884.
- Guigas B., Detaille D., Batandier C., Chauvin C., Fontaine E., Favier R. and Leverve X. (2005). Effect of the antidiabetic drug metformin on respiratory chain complex 1, PTP regulation and ROS production: consequence on cell death. Shock 23, 46-50 (Suppl 1).
- Detaille D., Guigas B., Chauvin C., Batandier C., Fontaine E., Wiernsperger N. and Leverve X. (2005). Metformin prevents high glucose-induced human endothelial cell death through a mitochondrial permeability transition-dependent process. Diabetes 54, 2179-2187.
- Batandier C., Guigas B., Detaille D., El-Mir M.Y., Fontaine E., Rigoulet M. and Leverve X. (2006). The ROS Production Induced by a Reverse-Electron Flux at Respiratory-Chain Complex I is Hampered by Metformin. J. Biomembr. Bioenerg. 38, 33-42.
- Guigas B., Taleux N., Foretz M., Detaille D., Andreelli F., Viollet B. and Hue L. (2007). AMP-activated protein kinase-independent inhibition of hepatic mitochondrial oxidative phosphorylation by AICA riboside. Biochem. J. 404, 499-507.
- Leverve X., Taleux N., Favier R., Batandier C., Detaille D., Devin A., Fontaine E. and Rigoulet M. (2007). Cellular energy metabolism and integrated oxidative phosphorylation. In : Molecular System Bioenergetics. Energy for life (Ed. by Saks V.) pp 11-27.
- Detaille D., El-Mir M.Y., Villanueva G.R., Delgado-Esteban M., Guigas B., Attia S., Fontaine E., Almeida A. and Leverve X. (2008). Neuroprotective role of antidiabetic drug metformin against apoptotic cell death in primary cortical neurons. J. Mol. Neurosci. 34, 77-87.
- Detaille D., Sanchez C., Sanz N., Guigas B., Lopez-Novoa J.M., Leverve X. and El-Mir Y. (2008). Interrelation between the inhibition of glycolytic flux by silibinin and the lowering of mitochondrial ROS production in perifused rat hepatocytes. Life Sciences 82, 1070-1076. - Oral communications and conferences -
- Detaille D., Wiernsperger N. and Devos P. Metformin’s effects on isolated Xenopus laevis oocytes. Laboratory of Fundamental and Applied Bioenergetics, INSERM E0221, University Joseph Fourier of Grenoble, Grenoble, France, April 2001. (invited by Pr. X. Leverve)
- Detaille D., Guigas B., Chauvin C., Fontaine E., Wiernsperger N. and Leverve X.M (2003). Protective effect of metformin on cellular death induced by an oxidizing agent, tBH, or by high glucose in both cultured human endothelial cell types. Presented at the third GFB Congress in Aussois, France.
- Detaille D. Optical and pharmacological tools to investigate the role of mitochondria during oxidative stress and subsequent cell death. University of Salamanca, Dpt of Physiology and Pharmacology, Salamanca, Spain, November 2006. (invited by Pr. Y. El-Mir) - Posters -
- Detaille D., Jacques Ph. and Thonart Ph. (1993) Biodegradation of the polycyclic aromatic hydrocarbons phenanthrene, naphtalene and biphenyl by bacteria isolated from a contaminated soil. Arch. Int. Physiol. Bioch. 102, B8. Presented at the 155th meeting of the SBBBM in Woluwé, Belgium
- Detaille D., Wiernsperger N. and Devos P. (1997) Identification of the mechanisms involved in the potentiating effects of metformin on insulin-induced glycogen synthase activity in Xenopus eggs. Diabetologia 40, A 154, 603. Presented at the 16th IDF Congress, Helsinki, Finland
- Detaille D., Wiernsperger N. and Devos P. New insights into the cellular mechanism underlying the anti- hyperglycaemic action of metformin (1997). Presented at the EASD Workshop, Geneva, Switzerland
- Detaille D., Wiernsperger N. and Devos P. (1998) Respective molecular effects of insulin and metformin on glucose uptake using the Xenopus oocyte model as expression system. Diabetologia 41, A 182, 707. Presented at the 34th EASD meeting, Barcelona, Spain
- Guigas B., Chauvin C., Batandier C., Detaille D., De Oliveira C., Fontaine E. and Leverve X. (2003). Metformin inhibits transition permeability and cell death. Diabetes Metab. 29, 243. Presented at the 18th IDF Congress, Paris, France; at the 3rd GFB Congress, Aussois, France; at the Research in Biology Conference, Grenoble, France
- Detaille D., Guigas B., Leverve X. and Wiernsperger N. (2003) Obligatory role of membrane events in the modulatory effect of metformin on the mitochondrial function. Diabetologia 46, A 297, 858. Presented at the 18th IDF Congress, Paris, France
- Detaille D., Guigas B., Chauvin C., Fontaine E., Wiernsperger N. and Leverve X. Protective effect of Metformin on apoptosis induced by oxidative stress (tBH) or high glucose in human endothelial cells: involvement of PTP (2003). Presented at the 3rd GFB Congress, Aussois, France; at the Research in Biology Conference, Grenoble, France
- Guigas B., Detaille D., Batandier C., Foretz M., Viollet B., Hue L. and Leverve X. (2006). Role de la mitochondrie et de l’AMP-activated protein kinase (AMPK) dans le mécanisme d’action cellulaire de la metformine (Colloque annuel de la SFBBM et 23ième forum Jeunes chercheurs)
- Argaud L., Dumas J-F., Detaille D., Cottet C., Leverve X. and Fontaine E (2007). Inhibition de l’ouverture du pore de transition de perméabilité mitochondriale des cellules endothéliales humaines par le préconditionnement ischémique. Arch. Mal. Cœur Vaiss. 100, 316.
- Recio JM., Villanueva GR., Naboulsi R., Sanchez C., Sanz N., Guigas B., Lopez-Novoa JM., Detaille D. and Leverve X. (2007) Silybin has antidiabetic effects by decreasing glucose-6-phosphate hydrolysis in perifused rat hepatocytes and inhibiting glucose-6-phosphatase activity. Diabetes Vasc Dis Res 4(Suppl 1), S146.
- Sanchez C., Recio J.M., Sanz N., Villanueva G.R., Lopez-Novoa J.M., Detaille D., Leverve X. and El-Mir Y. (2007). Oral antidiabetics thiazolidinediones directly inhibit hepatic gluconeogenesis in perifused liver cells. Diabetologia, 50 (Suppl. 1), S355.
- Detaille D., Sanchez C., Sanz N., Lopez-Novoa J.M., Guigas B., Rascon-Trincado M.V. y El-Mir M.Y. (2008). Interrelación entre la inhibición de la glicólisis producida por el medicamento hepatoprotector silibinina y la inhibición de la producción de radicales libres en hepatocitos de ratas perifundidos. Gastroenterol. Hepatol. 31 (Suppl.1), 119-120. Presented at the XXXIII congreso annual de la AEEH, Madrid, Spain
European Board of Gastroenterology & Hepatology - Sample Questions A 50-year-old man presented with haematemesis and melaena. He had a history of excess alcohol intake for many years. On examination, he was jaundiced with bilateral parotid enlargement, spider naevi and Dupuytren’s contractures. His pulse was 100 beats per minute and his blood pressure was 95/60 mmHg. He had ascites and
RAIN project (Wright et al ., 1993), the European EXMANand NITREX projects (Wright & Rasmussen, 1998) theGårdsjøn roof project in Sweden (Hultberg & Skeffington,1998), and the whole watershed manipulations in the US atthe Bear Brook Watershed in Maine (Norton & Fernandez,1999) and the Fernow Experimental Forest in West VirginiaO