Gastrointestinal Physiology Lab
The long-term objective of this research laboratory is to study mechanisms responsible for maintenance and restoration of the intestinal barrier, with the ultimate objective of pharmacologically restoring the mucosal barrier in patients suffering from diseases associated with increased intestinal permeability. Restoring the intestinal barrier would be of particular significance in patients suffering from diseases such as intestinal ischemia/reperfusion injury and gastric ulcer disease because of potential for severe medical complications such as sepsis that can occur with these diseases .
The laboratory collaborates extensively with the Leukocyte Biology Laboratory, the Moeser Lab and the Center for Gastrointestinal Biology and Disease at UNC-Chapel Hill.
Lab Members
Anthony Blikslager, Principal Investigator
919.513.7725
anthony_blikslager@ncsu.edu
Liara Gonzalez, Doctoral Candidate
Youngeeon Jin, Doctoral Candidate
Raphael Labens, Doctoral Candidate
Meghali Nighot, Postdoctoral Fellow
Tiffany Pridgen, Research Associate
Karen Young, Research Specialist
Undergraduate Students
Mary Brown, Biological Sciences Major
Heather Kashner, Biological Sciences Major
Research
We have two current research focuses:
The Role of ClC-2 in Intestinal Development and Repair
The central hypothesis for these studies is that the secretory protein ClC-2 recruits tight junction proteins to the apical lateral membrane, restoring intestinal barrier function.
Mechanisms of Non-steroidal Anti-inflammatory drugs in the Horse and Dog
The hypothesis of these studies is that COX inhibitors have species-specific COX selectivity, which have pronounced effects on the equine injured intestine and the canine stomach.
Recent Publications
Basic Science
Nighot PK, Blikslager AT. Chloride channel ClC-2 modulates tight junction barrier function via intracellular trafficking of occludin. Am J Physiol Cell Physiol 2012;302:C178-87.
Nighot M, Moeser A, Ueno R, Blikslager A. Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa. World J Gastroenterol. 2012;18:4684-92.
Cuppoletti J, Blikslager AT, Chakrabarti J, Nighot PK, Malinowska DH. Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors. BMC Pharmacol 2012;12:1-12.
Grosche A, Morton AJ, Graham AS, Sanchez LC, Blikslager AT, Polyak MM, Freeman DE Ultrastructural changes in the equine colonic mucosa after ischaemia and reperfusion. Equine Vet J 2011;43 Suppl 39:8-15.
Marshall JF, Bhatnagar AS, Bowman SG, Howard CM, Morris NN, Skorich DA, Redding CD, Blikslager AT. Evaluation of the cyclooxygenase selectivity of robenacoxib and its effect on recovery of ischaemia-injured jejunal mucosa in horses. Am J Vet Res 2011;72:226-32.
Marshall JF, Bhatnagar AS, Bowman SG, Morris NN, Skorich DA, Redding CD, Blikslager AT. The effects of a novel anti-inflammatory compound (AHI-805) on cyclooxygenase enzymes and the recovery of ischaemia injured equine jejunum ex vivo. Equine Vet J 2011;43 Suppl 39:106-11.
Smith F, Clark JE, Overman BL, Tozel CC, Huang JH, Rivier JE, Blikslager AT, Moeser AJ. Early weaning stress impairs development of mucosal barrier function in the porcine intestine. Am J Physiol Gastrointest Liver Physiol 2010;298:G352-G363.
Nighot PK, Blikslager AT. ClC-2 regulates mucosal barrier function associated with structural changes to the villus and epithelial tight junction. Am J Physiol Gastrointest Liver Physiol 2010;299:G449-56.
Nighot PK, Moeser A, Ali RA, Blikslager AT, Koci MD. Astrovirus infection induces sodium malabsorption and redistributes sodium hydrogen exchanger expression. Virology 2010; 401:146-54.
Kajino-Sakamoto R, Omori E, Nighot PK, Blikslager AT, Matsumoto K, Ninomiya-Tsuji J TGF-Activated Kinase 1 Signaling Maintains Intestinal Integrity by Preventing Accumulation of Reactive Oxygen Species in the Intestinal Epithelium. J Immunol 2010;185:4729-37.
Nighot PK, Moeser AJ, Ryan KA, Ghashghaei T, Blikslager AT. ClC-2 is required for rapid restoration of epithelial tight junctions in ischemic-injured murine jejunum. Exp Cell Res. 2009;315:110-8.
Moeser AJ, Nighot PK, Ryan KA, Simpson JE, Clarke LL, Blikslager AT. Mice lacking the Na+/H+ exchanger 2 have impaired recovery of intestinal barrier function. Am J Physiol Gastrointest Liver Physiol. 2008;295:G791-7.
Moeser AJ, Nighot PK, Roerig B, Ueno R, Blikslager AT. Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine. World J Gastroenterol 2008;14:6012-7.
Blikslager AT. Life in the gut without oxygen: adaptive mechanisms and inflammatory bowel disease. Gastroenterology. 2008;134:346-8.
Moeser AJ, Ryan KA, Nighot PK, Blikslager AT. Gastrointestinal dysfunction induced by early weaning is attenuated by delayed weaning and mast cell blockade in pigs. Am J Physiol 2007;293:G413-G421
Moeser AJ, Klok CV, Ryan KA, Wooten JG, Little D, Cook VL, Blikslager AT. Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig. Am J Physiol Gastrointest Liver Physiol 2007;292:G173-81.
Blikslager AT, Moeser AJ, Gookin JL, Jones SL, Odle J. Restoration of barrier function in injured intestinal mucosa. Physiol Rev. 2007;87:545-64.
Moeser A, Nighot PK, Engelke K, Ueno R, Blikslager AT. Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone. Am J Physiol Gastrointest Liver Physiol 2006;292:G647-56.
Moeser AJ, Nighot PK, Ryan KA, Wooten JG, Blikslager AT. Prostaglandin-mediated inhibition of Na+/H+ exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine. Am J Physiol Gastrointest Liver Physiol 2006;291:G885-94.
Moeser AJ, Haskell MM, Shifflett DE, Blikslager AT. ClC-2 Chloride Secretion Mediates Prostaglandin-induced Recovery of Barrier Function in Ischemia-Injured Porcine Ileum. Gastroenterology 2004;127:802-15.
Clinical Science
Davis W, Fogle CA, Gerard MP, Levine JF, Blikslager AT. Return to use and performance following exploratory celiotomy for colic in horses: 195 cases (2003-2010). Equine Vet J 2012;2042-3306.
Labens R, Blikslager AT. Precision of a photogrammetric method to perform 3D wound measurements compared to standard 2D photographic techniques in the horse. Equine Vet J 2012;45:41-46.
Vainio KM, Sykes BW. Blikslager AT. Primary gastric impaction in horses: A retrospective study of 20 cases (2005-2008). Equine Vet Educ 2011;23:186-90.
Sheats MK, Cook VL, Jones SL, Blikslager AT, Pease AP. Use of ultrasound to evaluate outcome following colic surgery for equine large colon volvulus. Equine Vet J 2010;42:47-52.
Bowman SG, Marshall JF, Blikslager AT. Demographic characteristics of horses donated to the North Carolina State University Equine Health Center, 1996-2008. J Am Vet Med Assoc 2010;236:1334-7.
Cook VL, Shults JJ, McDowell MR, Campbell NB, Davis JL, Marshall JF, Blikslager AT. Anti-inflammatory effects of intravenously administered lidocaine hydrochloride on ischemia-injured jejunum in horses. Am J Vet Res 2009;70:1259-1268.
Wooten JG, Blikslager AT, Marks SL, Law JM, Graeber EC, Lascelles BD. Effect of nonsteroidal anti-inflammatory drugs with varied cyclooxygenase-2 selectivity on cyclooxygenase protein and prostanoid concentrations in pyloric and duodenal mucosa of dogs. Am J Vet Res 2009;70:1243-1249.
Cook VL, Neuder LE, Blikslager AT, Jones SL. The effect of lidocaine on in vitro adhesion and migration of equine neutrophils. Vet Immunol Immunopathol. 2009;129:137-42.
Fogle CA, Gerard MP, Elce YA, Little D, Morton AJ, Correa MT, Blikslager AT. Analysis of Sodium Carboxymethylcellulose Administration and Related Factors Associated with Postoperative Colic and Survival in Horses with Small Intestinal Disease. Vet Surg 2008;37: 558-563.
Cook VL, Jones Shults J, McDowell M, Campbell NB, Davis JL, Blikslager AT. Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine. Equine Vet J 2008;40:353-7.
Wooten JG, Blikslager AT, Ryan KA, Marks SL, Law JM, Lascelles BD. Cyclooxygenase expression and prostanoid production in pyloric and duodenal mucosae in dogs after administration of nonsteroidal anti-inflammatory drugs. Am J Vet Res 2008;69:457-64.
Little D, Brown SA, Campbell NB, Moeser AJ, Davis JL, Blikslager AT. Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum. Am J Vet Res 2007 Jun;68:614-24.
Davis JL, Papich MG, Morton AJ, Gayle J, Blikslager AT, Campbell NB. Pharmacokinetics of etodolac in the horse following oral and intravenous administration. J Vet Pharmacol Ther 2007;30:43-8.
Davis JL, Little D, Blikslager AT, Papich MG. Mucosal permeability of water-soluble drugs in the equine jejunum: a preliminary investigation. J Vet Pharmacol Ther 2006;29:379-85.
Frederico LM, Jones SL, Blikslager AT. Predisposing factors for small colon impaction in horses and outcome of medical and surgical treatment: 44 cases (1999-2004). J Am Vet Med Assoc. 2006;229:1612-6.
Lascelles BD, Blikslager AT, Fox SM, Reece D. Gastrointestinal tract perforation in dogs treated with a selective cyclooxygenase-2 inhibitor: 29 cases (2002-2003). J Am Vet Med Assoc 2005;227:1112-7.
Little D, Tomlinson JE, Blikslager AT. Post operative neutrophilic inflammation in equine small intestine after manipulation and ischaemia. Equine Vet J 2005;37:329-35.
Tschetter JR, Blikslager AT, Little D, Howard RD, Woody SL, Beex LM, Crisman MV. Detection of differentially regulated genes in ischaemic equine intestinal mucosa. Equine Vet J 2005;37:319-24.
Morton AJ, Campbell NB, Gayle JM, Redding WR, Blikslager AT. Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis. Res Vet Sci 2005;78:189-192.
Tomlinson JE, Blikslager AT. Effects of the cyclooxygenase inhibitors flunixin and deracoxib on permeability of ischaemic-injured equine jejunum. Equine Vet J, 2005;37:75-80.
Campbell NB, Ruaux CG, Shifflett DE, Steiner JM, Williams DA, Blikslager AT. Physiologic concentrations of bile salts inhibit recovery of ischemic-injured porcine ileum. Am J Physiol Gastrointest Liver Physiol 2004;287:G399-407
Tomlinson JE, Wilder BO, Young KM, Blikslager AT. Systemic administration of flunixin meglumine or etodolac inhibits mucosal recovery of equine jejunum after ischemia. Am J Vet Res 2004;65:761-769.
Tomlinson JE, Blikslager AT. Effects of ischemia and the cyclooxygenase inhibitor flunixin on in vitro passage of lipopolysaccharide across ischemic-injured equine jejunum. Am J Vet Res 2004;65:1311-1450.
Education
The lab offers graduate training through the Comparative Biomedical Sciences program. CBS is a multidisciplinary graduate program with faculty who are employing state-of-the-art techniques to address a number of interesting scientific problems in the basic and applied biomedical sciences. The Comparative Biomedical Sciences Graduate Program is offered through the College of Veterinary Medicine at North Carolina State University and confers Master of Science (M.S.) and Doctor of Philosophy (Ph.D.) degrees. In addition, the laboratory participates in the Center for Comparative Medicine and Translational Research via the Mucosal Pathophysiology Core. We also collaborate with the Center for Biology and Gastrointestinal Disease, an NIH-funded Center linking GI researchers at UNC and NCSU.
Please contact the PI regarding training and funding opportunities.
GI journal club (PHY 820A)
Room RB256, Fridays, 8:00 am
Advances in Gastrointestinal Physiology (PHY/ CBS 764)
Every other year (next offered Fall 2013)
Tuesdays and Thursdays, 8:00-9:15am