RESEARCH TASKS

Basic research in biology at the Poitiers CHU consists in:

• Inserm ERM 0324 «Ischemia-reperfusion in renal transplantation »,  director  : Pr Gérard MAUCO
• EA 3805 « Myeloproliferative syndromes : cytogenetics, signaling, cellular cycle and immunitary response »,  director  : Pr Ali TURHAN
• EA 4331 « Inflammation, epithelial tissues and cytokines », director  : Pr Jean-Claude LECRON
• Inserm ERI 123 « Anti-infective pharmacology », director  : Pr William COUET
• CNRS UMR 6187 « Institute of cellular physiology and biology  », director : Pr Frédéric BECQ,  « Molecular pathology of addressing and signaling  » (PMAS) team, person in charge: Pr Alain KITZIS

INSERM ERM 0324 « Ischemia-reperfusion in renal transplantation »

Director: Pr Gérard MAUCO

Staff (as of 1/01/2010)

Last name, first name	Rank / Function (PU = university professor; PH = hospital practitioner	Main employer(s)	HDR (research director) (yes/no)
EUGENE Michel	pu-ph	CHU and University of Poitiers	Yes
FAVREAU Frédéric	university lecturer -ph	CHU and University of Poitiers	No
GOUJON Jean-Michel	pu-ph	CHU and University of Poitiers	Yes
HADJADJ Samy	pu-ph	CHU and University of Poitiers	Yes
HAUET Thierry	pu-ph	CHU and University of Poitiers	Yes
LEVILLAIN Pierre MAIXENT Jean-Michel	pu-ph pu	CHU and University of Poitiers University of Poitiers	Yes
MAUCO Gérard	pu-ph	CHU and University of Poitiers	Yes
RICHER Jean-Pierre	pu-ph	CHU and University of Poitiers	Yes
ROBERT René	pu-ph	CHU and University of Poitiers	Yes
SEGUIN François	pu	University of Poitiers	Yes
TOUCHARD Guy	pu-ph	CHU and University of Poitiers	Yes
BADET Lionel	pu-ph	Civil hospices of Lyon	Yes
BARROU Benoît	pu-ph	AP-HP (Paris hospitals)	Yes
HANNAERT Patrick	CR1 CNRS	CNRS	Yes
CAU Jérôme	ph	CHU of Poitiers	No
JAYLE Christophe	ph	CHU of Poitiers	no
CHATAURET Nicolas	Post-PhD	Contractual NRA	No
GIRAUD Sébastien	Engineer	CHU of Poitiers	No
THUILLIER Raphael	Engineer	CHU of Poitiers	No
FERNANDEZ Béatrice	Engineer	CHU of Poitiers
QUELLARD Nathalie AMETEAU Virginie	Engineer Technical assistant	CHU of Poitiers University of Poitiers	No
BOILDIEU Nadège	Technical assistant	University of Poitiers	No
CHAUVELON Françoise	Technician	CHU of Poitiers	No
JACQUART Maïté	Technician	CHU of Poitiers	No
JOFFRION Sandrine	Technician	CHU of Poitiers	No

PhD candidates (as of 1/01/2010)

Last name, first name	Thesis supervisor	Doctoral school of registration
CODAS Ricardo	BADET Lionel / HAUET Thierry	Bio-santé Poitiers
CHAILLOU Matthieu	MAIXENT Jean-Michel	Bio-Santé Poitiers/CIFRE
FARES Mourad	MAIXENT Jean-Michel	Bio-Santé Poitiers /CIFRE
GUILLAUD François	MAUCO Gérard / HANNAERT Patrick	Bio-santé Poitiers
GIRAUD Sébastien	HAUET Thierry	Bio-Santé Poitiers (CIFRE)
ROSSARD Ludivine	HAUET Thierry	Bio-Santé Poitiers
MALLET Vanessa	HAUET Thierry	Bio-Santé Poitiers

Research themes (as of 1/01/2010)

The research pursued in Inserm U1082 concerns renal transplantation. We are essentially interested in the process and consequences of ischemia-reperfusion (IR) and the mitigation of these consequences in view of improving transplantation conditions, of widening the field of usable organs and, in the end, of proposing new protocols. This IR sequence is an intrinsic component of the organ transplantation process, and it is associated with conservation in adequate solutions, at 4°C, which brings about a phase of hypothermic anoxia, followed by a period of reoxygenation at body temperature after reimplantation. However, this theoretical and simplified model of hypothermic ischemia is in fact completed by brief periods of ischemia at a progressively higher temperature during reheating of the transplanted organ, during anastomoses or, possibly for a longer lapse of time, before exeresis of the graft, at body temperature in cases where the hemodynamic stability of the donor is not guaranteed or, in extreme cases, in donors whose heart has stopped beating.

While renal transplantation is the preferred therapy in terminal chronic renal failure, it has encountered many practical obstacles connected with a penury of organs to be transplanted.This situation entails a need to develop protocols for retrieval, conservation, and post-operative monitoring: retrieval from aged donors and from donors whose heart has stopped beating, factors contributing to the aggravation of ischemia-reperfusion lesions.

Our approach associates preclinical experimentation on a model relatively close to the human being, namely the Large White pig, with in vitro and ex vivo experimentation. We also test different protocols of conservation with colloids (polyethylene glycols), anticoagulants and a number of other molecules (confidential, patent issued or pending).   In vitro and ex vivo, we are interested in the transmission mechanisms of the signal and the the gene/protein expression put into place on relevant cell models and in biopsies from the treated animals.

Different clinical studies are ongoing: NMR fluid spectroscopy, evolution of grafts in humans…

Principal results and their impact on treatment of patients:

• Development of conservation solutions yielding better recovery of function, presently industrially commercialized;
• Highlighting of the importance of protection from inflammation during transplantation, essentially via mechanisms acting on coagulation proteases;
• Definition of the prognosis criteria for follow-up on post-transplantation grafts.

Scientific publications  (from 2006 to 2010)

1. Favreau F, Zhu XY, Krier JD, Lin J, Textor SC, Lerman LO. “Revascularization of swine renal artery stenosis improves renal function but not the changes in vascular structure.” Kidney Int. 2010 (sous presse)

2. Guillaud F, Hannaert P, “A computational model of the circulating renin-angiotensin system and blood pressure regulation.” Acta Biotheor. 2010 (sous presse)

3. Brunet B, Hauet T, Hebrard W, Papet Y, Mauco G, Mura P. “Post-mortem redistribution of THC in the pig” Int. J. Legal Med. 2010 (sous presse)

4. Robert R, Guilhot J, Longeart PL, Jacob JP, Mauco G, Hauet T, Seguin F. “A pair analysis of the delayed graft function in kidney recipient: the critical role of the donor”. J. Crit. Care 2010 (sous presse)

5. Thuillier R, Favreau F, Celhay O,  Macchi L, Milin S, Hauet T “Thrombin inhibition during kidney ischemia-reperfusion reduces chronic graft inflammation and tubular atrophy” Transplantation 2010 (sous presse)

6. Favreau F, Thuillier R, Cau J, Milin S, Manguy E, Mauco G, Zhu X, Lerman LO, Hauet T. “Anti-thrombin Therapy During Warm Ischemia and Cold Preservation Prevents Chronic Kidney Graft Fibrosis in a DCD Model.” Am. J. Transplant. 10(1): 30-39. 2010

7. Thuillier R, Tillement JP, Hauet T. “Renal Protective Effect of Metabolic Therapy in Patients with Coronary Artery Disease and Diabetes: From Bench to Bed Side.” Curr. pharm. Design 15(8): 863-882. 2009

8. Jayle C, Faure JP, Thuillier R, Goujon JM, Richer JP, Hauet T. “Influence of nephron mass and a phosphorylated 38 mitogen-activated protein kinase inhibitor on the development of early and long-term injury after renal warm ischaemia.” Br. J. Surg. 96(7): 799-808. 2009

9. Giraud S, Thuillier R, Belliard A, Hebrard W, Nadeau C, Milin S, Goujon JM, Manguy E, Mauco G, Hauet T, Macchi L. “Direct Thrombin Inhibitor Prevents Delayed Graft Function in a Porcine Model of Renal Transplantation.” Transplantation 87(11): 1636-1644. 2009

10. Favreau F, Rossard L, Zhang K, Desurmont T, Manguy E, Belliard A, Fabre S, Liu J, Han ZQ, Thuillier R, Papadopoulos V, Hauet T. “Expression and modulation of translocator protein and its partners by hypoxia reoxygenation or ischemia and reperfusion in porcine renal models.” Am. J. physiol.-Renal physiol. 297(1): F177-F190. 2009

11. Dutheil D, Underhaug Gjerde A, Petit-Paris I, Mauco G, Holmsen H. “Polyethylene glycols interact with membrane glycerophospholipids: is this part of their mechanism for hypothermic graft protection?” J. Chem. Biol. Mar;2(1):39-49. 2009

12. Cau J, Favreau F, Zhang K, Febrer G, Regnault de la Motte G, Ricco JB, Goujon JM, Hauet T. “FR167653 improves renal recovery and decreases inflammation and fibrosis after renal ischemia reperfusion injury.” J. Vasc. Surg. 49(3): 728-740. 2009

13. Hauet T, Eugene M. “A new approach in organ preservation: potential role of new polymers.” Kidney Int. 74(8): 998-1003. 2008

14. Doucet C, Milin S, Favreau F, Desurmont T, Manguy E, Hebrard W, Yamamoto Y, Mauco G, Eugene M, Papadopoulos V, Hauet T, Goujon JM. “A p38 mitogen-activated protein kinase inhibitor protects against renal damage in a non-heart-beating donor model.” Am. J. physiol.-Renal. physiol. 295(1): F179-F191. 2008

15. Belliard A, Mauco G, Bonnet ML, Hauet T, Macchi L. “Melagatran prevents tissue factor expression in human platelets-monocyte heterotopic complexes.” Cell. Mol. Biol. 54: 1077-1082. 2008

16. Pierre SV, Lesnik P, Moreau M, Bonello L, Droy-Lefaix MT, Sennoune S, Duran MJ, Pressley TA, Sampol J, Chapman J, Maixent JM. “The standardized Ginkgo biloba extract Egb-761 protects vascular endothelium exposed to oxidized low density lipoproteins.”Cell. Mol. Biol. (Noisy-le-grand). Oct 26;54 Suppl:OL1032-42. 2008

17. Kalifa J, Maixent JM, Chalvidan T, Dalmasso C, Colin D, Cozma D, Laurent P, Deharo JC, Djiane P, Cozzone P, Bernard M. “Energetic metabolism during acute stretch-related atrial fibrillation.” Mol. Cell. Biochem. Oct;317(1-2):69-75. 2008

18. Thomas SR, Baconnier P,  Fontecave J, Francoise JP, Guillaud F, Hannaert P,  Hernandez A, Le Rolle V,  Maziere P, Tahi F, White RJ (alphabetical order after SR Thomas). “SAphIR: a physiome core model of body fluid homeostasis and blood pressure regulation.”philos. Transact. A Math. phys. Eng. Sci. 366(1878):  3175-97 2008

19. Guillaud F, Hannaert P. “Dynamic simulation of mitochondrial respiration and oxidative phosphorylation: comparison with experimental results.” Acta Biotheor.  56(1-2): 157-72 2008.

20.  Rigoard P, Tartarin F, Buffenoir K, Chaillou M, Fares M, D’Houtaud S, Wager M, Giot JP, Quellard N, Fernandez B, Lapierre F, Maixent JM. “The Na, K-ATPase alpha3-isoform specifically localizes in the Schmidt-Lanterman incisures of human nerve. Cell. Mol. Biol.” (Noisy-le-grand). Nov 19;53 Suppl:OL1003-9. 2007

21. Thomas SR, Abdulhay E, Baconnier P, Fontecave J, Francoise JP, Guillaud F, Hannaert P, Hernandez A, Le Rolle V, Maziere P, Tahi F, Zehraoui F (alphabetical order after SR Thomas). “SAphIR – a multi-scale, multi-resolution modeling environment targeting blood pressure regulation and fluid homeostasis.”IEEE Eng. Med. Biol. Soc. 1:6648-51 2007

22. El Aoufi S, Gendre P, Sennoune SR, Rigoard P, Maixent JM, Griene L. “A high calorie diet induces type 2 diabetes in the desert sand rat (Psammomys obesus). “Cell. Mol. Biol. (Noisy-le-grand). Jul 21;53 Suppl:OL943-53. 2007

23. Kalifa J, Bernard M, Gout B, Bril A, Cozma D, Laurent P, Chalvidan T, Deharo JC, Djiane P, Cozzone P, Maixent JM. “Anti-arrhythmic effects of I (Na), I (Kr) and combined I (Kr)-I (CaL) blockade in an experimental model of acute stretch-related atrial fibrillation.” Cardiovasc. Drugs Ther. Feb;21(1):47-53. 2007

24. Jayle C, Favreau F, Zhang KQ, Doucet C, Goujon JM, Hebrard W, Carretier M, Eugene M, Mauco G, Tillement JP, Hauet T. “Comparison of protective effects of trimetazidine against experimental warm ischemia of different durations: early and long-term effects in a pig kidney model.” Am. J. physiol.-Renal physiol. 292(3): F1082-F1093. 2007

25. Doucet C, Zhang K, Desurmont T, Hebrard W, Scepi M, Nadeau C, Cau J, Leyre P, Febrer G, Carretier M, Richer JP, Papadopoulos V, Hauet T, Burucoa C, Goujon JM. “Influence of warm ischemia time on peripheral-type benzodiazepine receptor: A new aspect of the role of mitochondria.” Nephron Exp. Nephrol 107(1): E1-E11. 2007

26. Giraud S, Claire B, Eugene M, Debre P, Richard F, Barrou B. “”A new preservation solution increases islet yield and reduces graft immunogenicity in pancreatic islet transplantation.” (vol 83, pg 1397, 2007).” Transplantation 84(4): 561-561. 2007

27. Zhang KQ, Desurmont T, Goujon JM, Favreau F, Cau J, Deretz S, Mauco G, Carretier M, Papadopoulos V, Hauet T. “Modulation of peripheral-type benzodiazepine receptor during ischemia reperfusion injury in a pig kidney model: A new partner of leukemia inhibitory factor in tubular regeneration.” J. Am. Coll. Surg. 203(3): 353-364. 2006

28. Zhang KQ, Demeure O, Belliard A, Goujon JM, Favreau F, Desurmont T, Mauco G, Barriere M, Carretier M, Milan D, Papadopoulos V, Hauet T. “Cloning, sequencing, and chromosomal localization of pig peripheral benzodiazepine receptor: three different forms produced by alternative splicing.” Mamm. Genome 17(10): 1050-1062. 2006

29. Badet L, Eugene M,  Hauet T, Barrou B. “The use of preservation solutions in renal transplantation.” Prog. Urol. 16:25-31. 2006

30. Neuzillet Y, Giraud S, Lagorce L, Eugene M, Richard F, Debre P, Barrou B. “In vivo comparison of preservation of murine islets of Langerhans.” Prog. Urol. 16(1): 73-77. 2006

31. Jayle C, Milinkevitch S, Favreau F, Doucet C, Richer JP, Deretz S, Mauco G, Rabb H, Hauet T. “Protective role of selectin ligand inhibition in a large animal model of kidney ischemia-reperfusion injury.” Kidney Int. 69(10): 1749-1755. 2006

32. Godet C, Goujon JM, Petit I, Lecron JC, Hauet T, Mauco G, Carretier M, Robert R. “Endotoxin tolerance enhances interleukin-10 renal expression and decreases ischemia-reperfusion renal injury in rats.” Shock 25(4): 384-388. 2006

33. Dutheil D, Rioja-Pastor I, Tallineau C, Goujon JM, Hauet T, Mauco G, Petit-Paris I. “Protective effect of PEG 35000 Da on renal cells: Paradoxical activation of JNK signaling pathway during cold storage.” Am. J. Transplant. 6(7): 1529-1540. 2006

34. Genesca M, Ivorra A, Sola A, Palacios L, Goujon JM, Hauet T, Villa R, Aguilo J, Hotter G. “Electrical bioimpedance measurement during hypothermic rat kidney preservation for assessing ischemic injury.” Biosens. Bioelectron. 20(9): 1866-1871. 2005

35. Hauet T, Yao ZX, Bose HS, Wall CT, Han Z, Li W, Hales DB, Miller WL, Culty M, Papadopoulos V. “Peripheral-type benzodiazepine receptor-mediated action of steroidogenic acute regulatory protein on cholesterol entry into leydig cell mitochondria.” Mol. Endocrinol. Feb;19(2):540-54. 2005

36. Giraud S, Hauet T, Eugene M, Mauco G, Barrou B. “A New Preservation Solution (SCOT 15) Improves the islet Isolation process from pancreata of Non-Heart-Beating Donors: A Murine Model.” Transplant. Proc. 41(8): 3293-3295. 2009   8th Annual Congress of the French-Speaking-Society-of-Transplantation OCT, 2008 Quebec City, CANADA

37. Codas R, Badet L, Eugene M, Giraud S, Thuiller R, Hauet T. “Evaluation of pulsatile Perfusion Machine RM3 for Kidney Preservation in a Swine Model of Renal Autotransplantation.” Transplant. Proc. 41(8): 3296-3298. 2009  8th Annual Congress of the French-Speaking-Society-of-Transplantation OCT, 2008 Quebec City, CANADA

38. Neuzillet Y, Giraud S, Lagorce L, Eugene M, Debre P, Richard F, Barrou B. “Effects of the molecular weight of peg molecules (8, 20 and 35 KDA) on cell function and allograft survival prolongation in pancreatic islets transplantation.” Transplant. Proc. 38(7): 2354-2355. 2006   5th Annual Conference of the French-Speaking-Society-of-Transplantation DEC 07-10, 2005 Tours, FRANCE

39. Brunet B, Doucet C, Venisse N, Hauet T, Hebrard W, Papet Y, Mauco G, Mura P. “Validation of Large White Pig as an animal model for the study of cannabinoids metabolism: Application to the study of THC distribution in tissues.” Forensic Sci.Int. 161(2-3): 169-174. 2006   43rd International Conference of the International-Association-of-Forensic-Toxicologists (TIAFT) AUG 29-SEP 02, 2005 Seoul, SOUTH KOREA

40. Rigoard P, Buffenoir K, Chaillou M, Fares M, Da Costa L, Boildieu N, Seguin F, Lapierre F, Maixent JM, Bauche S, Koenig J, Hantaï D. “Morphological study of CNS lesions and the consequences on rat neuromuscular junction and peripheral nerve using confocal laser scanning microscopy and Koelle’s technique. “Neurochirurgie. Mar;55 Suppl 1:S110-23. 2009

41. Rigoard P, Buffenoir K, Bauche S, Fares M, Koenig J, Hantaï D, Giot JP, Seguin F, Huze C, Schaeffer L, Maixent JM. “Tools and techniques dedicated to neuromuscular junction observation.” Neurochirurgie. Mar;55 Suppl 1:S43-8. 2009

42. Rigoard P, Bauche S, Buffenoir K, Da Costa L, Boildieu N, Seguin F, Koenig J, Lapierre F, Maixent JM. “Pathophysiological, molecular and metabolic changes at the neuromuscular junction and the peripheral nerve after central nervous system lesions in humans.” Neurochirurgie. Mar;55 Suppl 1:S135-47. 2009

43. Rigoard P, Buffenoir K, Fares M, Chaillou M, Da Costa L, Boildieu N, Seguin F, Huze C, Schaeffer L, Lapierre F, Maixent JM. “Toward a metabolic approach of the central pattern generator concept in a spinal rat model.” Neurochirurgie. Mar;55 Suppl 1:S124-34. 2009

44. Rigoard S, Wager M, Buffenoir K, Bauche S, Giot JP, Maixent JM, Rigoard P. Major mechanisms involved in the synaptic transmission of the neuromuscular apparatus. Neurochirurgie. Mar;55 Suppl 1:S22-33. Review. 2009

45. Rigoard P,  Chaillou M, Fares M, Sottejeau Y, Giot JP, Honfo-Ga C, Rohan J, Lapierre F, Maixent JM. “Energetic applications: Na+/K+-ATPase and neuromuscular transmission.” Neurochirurgie. Mar;55 Suppl 1:S92-103. Review. 2009.

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