Research Interests

Dr. Taché’s laboratory is involved in the understanding of brain-gut interactions as it relates to the neuroanatomical substrate and biochemical coding of stress-induced alterations of gut function and viscerosensibility. She is particularly pursuing research on the role of corticotropin releasing factor (CRF) signaling pathways both in the brain and the gut in mediating gastrointestinal motor alterations and visceral hypersensitivity in response to stress exposure in collaboration with Drs. Million, Wang, and Adelson viscerosensibility.

She is particularly pursuing research on the role of corticotropin releasing factor (CRF) signaling pathways both in the brain and the gut in mediating gastrointestinal motor alterations and visceral hypersensitivity in response to stress exposure in collaboration with Drs. Million, Wang, and Adelson. She is also pursuing research on the implication of CRF receptors and ghrelin in immune challenge-induced alterations of gut transit and food intake. Their research relates to PNI as they are pursuing investigations on the interaction between immune mediators that activate CRF signaling pathways in both the brain and gut and gastrointestinal function along with how CRF peptides modulate mast cell activity in the gut.

GRANTS

1. NIH

RO1 DK 33061 Taché (PI) 07/01/95 – 06/30/08

NIH/DDK

Corticotropin Releasing Factor: Actions on GI Function

The overall goals are to define the role of the paraventricular nucleus of the hypothalamus and locus coeruleus underlying CRF and IL-1 actions in the brain to induce alterations of gastric and colonic motor function and their implications at these brain sites to the stress response in rats.

Role: PI

DK 41301 Rozengurt (PI) 12/01/99 – 11/30/04

NIH/DDK Center Grant

Animal Core Y. Taché/J. Kaunitz

To provide guidance and expertise in the performance of in vivo studies and to assess gastric secretory and motor functions in collaboration with other cores; to test in vivo biological activity of antibodies.

Role: PI

RO1 DK 57238 Taché (PI) 09/01/00 – 08/30/05

NIH/DDK

Peripheral Mechanisms of Stress-induced Activation of Colonic Motor unction.

The objectives of this grant are to establish the receptors and pathways through which stress neurotransmitters activate colonic motor function.

Role: PI

NIH 1P50 DK 64539 Mayer (PI) 09/30/02 – 08/31/07

Women's Health and Functional Visceral Disorder Center

P2: Sex Differences in the Colonic Responses to Stress: Role of CRF Pathways

The objectives are to establish the role and mechanisms of the CRF system in sex related differences on visceral pain responses.

Role: Co- Investigator

1 R24 AT002681 (Mayer) 2004 – 2009

NIH/NCCAM

Mind/Brain/Body Interactions in Stress-Related Disorders

utilize the resources of the cores as well as the expertise of the involved faculty. In addition, a career development program in form of a Named New Investigator award is included, as well as several developmental and public infrastructure components.

Role: Co-PI

R21 NS 044187 (Li, PI; Taché, Co-PI) 07/01/02 – 06/30/05

NIH

Corticotropin-Releasing Factor,Role in Cyclic Vomiting Syndrome

2. VA

VA MERIT AWARDTaché (PI) 04/01/00 – 03/30/09

Peripheral Mechanisms of Post-Operative Ileus

To assess the mechanisms underlying post-operative gastric stress with a specific emphasis on the role of CRF signaling pathways.

Role: PI

VA Research Career Scientist Award (Taché, PI) 11/01/03 – 10/31/08

3. Private Industry

Repligen Co. (Taché, PI) 08/01/02 – 08/01/04

Mechanisms by which Peripheral Secretion Influences Neuronal Activity in Rat Brain

Novartis (Taché, PI) 05/01/01 – 04/01/05

Distribution of CRF Ligands and Their Receptors in the Gastrointestinal Tract and Autonomic/Visceral Ganglia

Aventis (Taché, PI) 05/01/01 – 04/01/05

Influence of Selective CRF Subtype 1 Receptor Antagonist, AVE 1960 in Stress-Related Activation of Colonic Motor Function and Hypersensitivity in Rats

Lilly (Taché, PI) 02/01/01 – 04/01/05

Influence of Eli Lilly Compounds on Models of Diarrhea Compared with VIP in Rats.

PUBLICATIONS

RESEARCH PAPERS - (PEER REVIEWED)

2003

• Chen C-Y, Doong M-L, Rivier JE, Vale W, Taché Y. Intravenous urocortin II decreases blood pressure through CRF2 receptors in rats. Regul. Pept. 113:125-130 (2003)

• Maillot C, Wang L, Million M, Taché Y. Intraperitoneal corticotropin-releasing factor and urocortin induce Fos expression in brain and spinal autonomic nuclei and long lasting stimulation of colonic motility in rats. Brain Res. 974:70-81 (2003).

• Basa NR, Wang L, Artega JR, Heber D, Livingston EH, and TachéY. Bacterial lipopolysaccharide shifts fasted plasma ghrelin to postprandial levels in rats. Neurosci. Lett. 343:25-28 (2003).

• Piqueras L, Taché Y. and Martinez V. Somatostatin receptor type 2 mediates bombesin-induced inhibition of gastric acid secretion in mice. J. Physiol. 549(Pt 3):889-901(2003).

• Million M, Grigoriadis DE, Sullivan S, Crowe PD, McRoberts JA, Zhou H, Saunders PR, Maillot C Mayer EM, and Taché Y. A novel water-soluble selective CRF 1 receptor antagonist, NBI 35965, blunts stress-induced visceral hyperalgesia and colonic motor function in rats. Brain Res. 985:32-42 (2003).

• Luckey A, Wang L, Jamieson PM, Basa NR, Million M, Czimmer J, Vale W and Taché Y. Corticotropin-releasing factor receptor 1-deficient mice do not develop postoperative gastric ileus. Gastroenterology 125: 262-268 (2003).

• Ruter J, Kobelt P, Tebbe JJ, Avsar Y, Veh R, Wang L, Klapp BF, Wiedenmann B, Taché Y and Monnikes H. Intraperitoneal injection of ghrelin induces Fos expression in the paraventricular nucleus of the hypothalamus in rats. Brain Res. 991:26-33 (2003)

2004

• Chatzaki E, Murphy BJ, Wang L, Million M, Ohning GV, Crowe PD, Petroski R, Taché Y, and Grigoriadis DE. Differential profile of CRF receptor distribution in the stomach and duodenum assessed by newly developed CRF receptor antibodies. J. Neurochem. 88:1-11 (2004)

• Adelson SW, Million M, Kanamoto K, Palanca T, and Taché Y. Coordinated gastric and sphincter motility evoked by intravenous CCK-8 as monitored by ultrasnonomicrometry in rats. Am. J. Physiol. 286:G321-G332 (2004).

• Martinez V, Wang L, Rivier J, Grigoriadis D and Taché Y. Central CRF, urocortins and stress increase colonic transit via CRF 1 receptors while activation of CRF 2 receptors delays gastric transit in mice. J. Physiol. 556.1: 221-234 (2004)

• Piqueras L, Taché Y, and Martinez V. Peripheral PACAP inhibits gastric acid secretion through a somatostatin receptor 2 in mice. Brit. J. Pharmacol. 142:67-78 (2004)

• Chatzaki E, Crowe PD, Wang L, Million M, Taché Y, Grigoriadis DE. CRF receptor type 1 and 2 expression and anatomical distribution in the rat colon. J. Neurochem. 90:309-316 (2004)

• Wang YH, Taché Y, Harris AG, Kreutner W, Daly A, and Wei JY. Desloratadine prevents compound 48/80-induced mast cell degranulation: visualisation using a vital fluorescent dye technic. Allergy (in press).

• Yang H, Wang L, Wu VS, Tay J, Goulet M, Boismenu R. Czimmer J, Wang Y, Wu S, Ao Taché Y. Peripheral secretin-induced Fos expression in the rat brain is largely vagal dependent. Neurosciences (in press).

• Piqueras L, Taché Y and Martinez V. Galanin inhibits gastric acid secretion through a somatostatin-independent mechanism in mice. Peptides (in press)

REVIEWS AND BOOK CHAPTERS

2003

• Luckey A. Livingston E and Taché Y. Post-operative ileus: mechanisms and treatment. Arch. Surg. 138:203-214 (2003)

• Martinez V and Taché Y. Vomiting Center. In Encyclopedia of the Neurological Sciences. Elsevier Sciences ( USA) pp 729-731 (2003).

• Go VLW and Taché Y . Gastrointestinal dysfunction and anorexia: role of brain-gut axis. In The Control of Food and Fluid Intake in Health and Disease. Eds. MJ Farthing and D Mahalanabis. . Nestec Ltd., Vevey/Lippincott Williams & Wilkins, USA. Nestlé Nutrition Workshop Series. Pediatric Program 51: 31-44 (2003).

• Taché Y and Yang Y. Vagal regulation of gastric function by brain neuropeptides. Encyclopedia of Hormones. Eds Henry HL and Norman AW. Elsevier Science.( USA), pp 546-554 (2003).

• Zorrilla EP, Taché Y and Koob GF. Nibbling at CRF receptor control of feeding and gastrocolonic motility. Trends Pharmacol. Sci. 24:421-427 (2003)

• St-Pierre DH, Wang L and Taché Y. Ghrelin: a novel player in the gut-brain regulation of growth hormone and energy balance. NIPS 18:242-246 (2003)

• Martinez V, Wang, L and Taché Y. Corticotropin releasing factor (CRF) receptors and stress-related gastrointestinal motor function. 11th International Conference on Ulcer Research Editors: P Sikiric, S Seiweth, G Mozsik, Tarakawa, K Takeuchi., Monduzzi Editore, Bologna, pp 189-199 (2003).

2004

• MatinezV and Taché Y Somatostatin and its receptors in the gastrointestinal tract. Encyclopedia of Gastroenterology. Elsevier 426-433 (2004)

• Taché, Y. Central vagal regulation of gastrin secretion. In Gastrin in the new millenium. Eds JL. Merchant and T. Wang, CURE Foundation, Los Angeles, CA pp 41-53, (2004)

• Y. Taché and M. Perdue. Role of peripiheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function. Neurogastroenterol. Motil. 16: (Suppl. 1) 137-142 (2004).

• Taché Y, Martinez V, Wang L, Million M. CRF 1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensibility: implications for irritable bowel syndrome. Brit. J. Pharmacol. 141:1321-1330 (2004)

• Million M and Taché Y. Stress-related alterations of gastrointestinal function: Peripheral pathways. In Pathophysiology of the enteric nervous system: a basis for understanding functional diseases. Eds Spiller R and Grundy D. Blackwell Publishing, Oxford, UK. In press

• Taché Y. Corticotropin releasing receptor antagonists: potential future therapy in gastroenterology? Gut 53:919-921 (2004)

• Martinez V, Wang L, Million M, Rivier J and Taché Y. Urocortins in the regulation of gastrointestinal motor function and visceral pain. Peptides (in press)

• Wood JD, Grundy D, Al-Chaer E, Aziz Q, Collins S, Ke M and Taché Y. Rome III. Fundamentals of neurogastroenterology: basic science. Gut 53: (2004)

• Taché Y. Trends in neurogastroenterology research. In: International Trends in the Gastrointestinal Research 1960-2005: From Basic Sciences to Clinical Perspectives. Ed. By G. Mózsik (in press)

ABSTRACTS

2003

• Luckey III AE, Czimmer J, Million M, Basa N, Taché Y. Peripheral Injection of a Corticotropin-Releasing Factor (CRF) Subtype 1 Antagonist, CP-154-526, Prevents Peripheral CGRP-induced Delayed Gastric Emptying in Rats. Gastroenterology 124 (Suppl. 1):A-137 (2003)

• Saunders P, Million M, Miampamba M, Wang L, Czimmer J, Taché Y. Urocortin II (Ucn II) Suppresses CRF-Induced Activation of Rat Colonic Motor Function and Myentric Neurons. Gastroenterology 124 (Suppl. 1):A-139 (2003)

• Piqueras L, Taché Y, Martinez V. Bombesin-Induced Inhibition of Gastric Acid Secretion Is Mediated by Somatostatin: Evidence in SSTR2 Knockout Mice. Gastroenterology 124 (Suppl. 1):A-141 (2003)

• Luckey III AE, Million M, Basa N, Czimmer J, Taché Y. The selective corticotropin-releasing factor receptor one subtype (CRF1) antagonist, CP-154, 526 (CP) prevents celiotomy-induced delayed gastric emptying (GE) in mice. Gastroenterology 124 (Suppl. 1):A-580 (2003)

• Piqueras L, Taché Y, Martinez Sr. V. Somatostatin Receptor Type 2 (SSTR2) Knockout and Antagonist Blocked PACAP-Induced Inhibition of gastric Acid Secretion in Mice. Gastroenterology 124 (Suppl. 1):A-608 (2003)

• Czimmer J, Million M, Taché Y. Central human Urocortin-II (h Ucn II) and h/rat CRF delay gastric emptying through distinct neural pathways in rats. Gastroenterology 124 (Suppl. 1):A-612 (2003)

• Chatzaki E, Murphy BJ, Wang L, Million M, Ohning G, Crowe PD, Petroski R, Taché Y, Grigoriadis DE. Corticotropin Releasing Factor (CRF) Receptors in the Upper Gastrointestinal (GI) Tract of the Rat: Maping of Expression Using Newly Developed Specific Antibodies. Gastroenterology 124 (Suppl. 1):A-614 (2003)

• Yang H, Wang L, Boismenu R, Goulet M, Wang Y, Taché Y. Peripheral Secretin-Induced Fos Expression in Rat Brain: Pathways and Neurochemical Phenotypes. Gastroenterology 124 (Suppl. 1):A-614 (2003)

• Adelson DW, Million M, Kosoyan H, Taché Y. Intravenous Urocortin II Contracts Pylorus, Antrum, and Lower Esophageal Sphincter and Reduces Intragastric Pressure in Urethane-Anesthetized Rats. Gastroenterology 124 (Suppl. 1):A-678 (2003)

• Million M, Wang L, Taché YF. Human Urocortin II (hUcn II) Blunts Colorectal Distention Induced Visceromotor Response and Activation of ERK in Spinal Neurons of Rats. Gastroenterology 124 (Suppl. 1):A-46 (2003)

• Luckey AE, Suto G, Kiraly A, Taché Y. Endotoxin (EDX)-induced inhibition of gastric emptying (GE) involves interleukin-1 8 (IL-1 8 ) and CRF 2 Receptors. FASEB 17:A-41 (2003)

• Basa N, Wang L, Arteaga J, Heber D, Livingston E, Taché Y. Effect of lipopolysaccharide administration of peripheral ghrelin levels in rats. FASEB 17:A-809 (2003)

2004

• Wang Y, Million M, Wang L, Yuan P-Q, McRoberts JA, Wei JY, Taché Y. A selective CRF2 receptor agonist, urocortin 2, blunts colorectal distension-induced activation of rat inferior splanchnic afferents in vitro. Gastroenterology 126:A-592 (2004)

• Yuan P-Q, Wu V, Taché Y. CRF receptor type 1 and 2 (CRF1 and CRF2) in rat colon: Differential distribution, expression and regulation by endotoxin. Gastroenterology 126:A-5 (2004)

• Yuan P-Q, Wu SV, Luckey A, Scott D, Taché Y. Endotoxin inhibits gastric emptying through peripheral CRF2 receptor and down regulates gastric CRF2 gene expression in rats. Gastroenterology 126:A-48 (2004)

• Wang L, Basa NR, Shaikh A, Luckey A, Heber D, Wu SV, Taché YF. Bacterial lipopolysaccharide (LPS) inhibits plasma ghrelin in fasted rats: Mechanisms and role in the inhibition of gastric emptying and feeding. Gastroenterology 126:A-145 (2004)

• Luckey A, Wang L, Million M, Czimmer J, Taché YF. CRF receptor 1 in the brain plays a role in postoperative ileus in rats. Gastroenterology 126:A-274 (2004)

• Mulugata M, Saunders PR, Taché Y. Peripheral urocortin 2 suppresses water avoidance stress and CRF-induced colonic motor stimulation in rats. Gastroenterology 126:A-587 (2004)

• Adelson DW, Kosoyan H, Chun E, Million M, Taché Y. Vago-vagal reflex responses to iv ghrelin and CCK in rats: A combined ultrasonometry-dual nerve recording study. Gastroenterology 126:A-588 (2004)

• Million M, Wang L, Coste S, Stenzel-Poore M, Buffington CAT, Taché Y. Enhanced colonic and urinary responses to novel stressors in CRF-overexpressing mice. Soc Neurosci Abstr in press (2004)

• Wu SV, Peng YL, Wang L, Taché Y. Identification of rat corticotropin releasing factor (CRF) receptor 2 (CRF 2) variants in the lower esophageal sphincter and regulation by vagotomy. Soc Neurosci Abstr in press (2004)

• Yuan P, Million M, Kimura H, Grigoriadis DE, Taché Y. Central corticotropin releasing factor (CRF)-induced stimulation of colonic motor function involves activation of colonic myenteric cholinergic and distal colonic nitrinergic neurons in rats. Soc Neurosci Abstr in press (2004)

• Neslon AG, Mulugeta M, Kosoyan HP, Chaudhuri G, Taché Y. Chronic 17-epiestriol potentiates peripheral CRF-induced colonic motility in rats. Soc Neurosci Abstr in press (2004)

• Wang L, Shaikh A, Pambukhchian K, Heber D, Taché Y. Urocortins increase levels of ghrelin and glucose through autonomic nerves or CRF 2 receptors. Soc Neurosci Abstr in press (2004)
  
• ·Wang L, Shaik A, Basa N, Heber D, Taché Y. Different stress regulate circulating ghrelin levels in rats. Regul Pept in press (2004)

Contact
Tache, Yvette F.
Med-Div of Digestive Dis,CURE
VA Greater LA Healthcare Sys Bldg 115,Rm 117B
mail code: 179247
phone: 310-312-9275, 310-268-3859
fax: 310-268-4963
email: