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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
Lab Members: Tiffany Pridgen, Anthony Blikslager, Mary Brown, Liara Gonzalez

lab members
Lab Members: Tiffany Pridgen, Liara Gonzalaz, Youngeeon Jin

Lab Members

Anthony Blikslager, Principal Investigator, 919.513.7725, anthony_blikslager@ncsu.edu
Tiffany Pridgen, Lab Manager

Graduate Students
Shante Bryant
Liara Gonzalez
Youngeeon Jin

Undergraduate Students
Mary Brown, Biological Sciences Major, NC State University
Asia Hilliard, Microbiology, NC State University

Visiting Students
Sanjay Gadi, High School Intern

Ongoing Research

“The training I have acquired as a veterinary clinician-scientist has contributed to my success in developing and utilizing the pig as a translational model to study intestinal stem cell biology. My experience as a large animal surgeon has specifically inspired my interest in improving therapies for gastrointestinal ischemic injury. “ - Liara Gonzalez

Identification of stem, progenitor, and transit amplifying cells in procine small intestine and colon
Identification of stem, progenitor, and transit amplifying cells in porcine small intestine and colon are shown.

“ I have two current research focuses. The first area of my research is the mechanisms underlying regulation of tight junctions in intestinal hypoxic injury and repair. Secondly, I am interested in examining the role of lubiprostone, a ClC-2 activator, in an experimental mouse model of colitis, and also hypoxic injury in an in vitro model utilizing a human colon cell line.” - Youngeeon Jin

The Role of ClC-2 in Intestinal Development and Repair

blikslager lab picture
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.

“I am broadly interested in immunology, the mechanisms that underlie infectious disease, and gastrointestinal physiology. I am currently working to develop a mouse model in which symptoms of human Irritable Bowel Syndrome (IBS) can be replicated and examined collectively by comparing post-infectious and post-inflammatory models for their ability to induce two major problematic symptoms that IBS patients experience, intestinal motility dysfunction and visceral hypersensitivity. Once a model is selected, I'll evaluate histopathological changes and investigate additional symptoms such as alterations in intestinal permeability and secretion. The ultimate goal of this project is to identify causal genetic links that contribute to the development of IBS using the Collaborative Cross genetic reference panel.” - Shante Bryant

Recent Publications

Nighot P, Young K, Nighot M, Rawat M, Sung EJ, Maharshak N, Plevy SE, Ma T, Blikslager A. Inflamm Bowel Dis. 2013 Sep 11.[Epub ahead of print] PMID:24030525

Jacobi SK, Moeser AJ, Blikslager AT, Rhoads JM, Corl BA, Harrell RJ, Odle J. World J Gastroenterol. 2013 Aug 21;19(31):5094-102. doi: 10.3748/wjg.v19.i31.5094. PMID:23964143

Blikslager AT. Feeding intravenously saves the patient but starves the gut. J Physiol. 2013 Aug 1;591(Pt 15):3673. doi: 10.1113/jphysiol.2013.260703. No abstract available. PMID:23908408

Gonzalez LM, Williamson I, Piedrahita JA, Blikslager AT, Magness ST. PLoS One. 2013 Jun 28;8(6):e66465. doi: 10.1371/journal.pone.0066465. Print 2013.PMID: 23840480

Labens R, Redding WR, Desai KK, Vom Orde K, Mansmann RA, Blikslager AT. Validation of a photogrammetric technique for computing equine hoof volume. Vet J. 2013 May 9. doi:pii: S1090-0233(13)00176-7. 10.1016/j.tvjl.2013.04.005. [Epub ahead of print] PubMed PMID: 23664155.

Blikslager AT. Misoprostol: is it safety or a lack of understanding that prevents its more frequent usage? Equine Vet J. 2013 Jan;45(1):8. doi: 10.1111/evj.12017. PubMed PMID: 23231384.

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 Sep 14;18(34):4684-92. PubMed PMID: 23002337; PubMed Central PMCID: PMC3442206.

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. 2013 Mar;45(2):224-8. doi: 10.1111/j.2042-3306.2012.00615.x. Epub 2012 Aug 1. PubMed PMID: 22853644.

Jacobi SK, Moeser AJ, Corl BA, Harrell RJ, Blikslager AT, Odle J. Dietary long-chain PUFA enhance acute repair of ischemia-injured intestine of suckling pigs. J Nutr. 2012 Jul;142(7):1266-71. doi: 10.3945/jn.111.150995. Epub 2012 May 23. PubMed PMID: 22623387.

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 May 3;12:3. doi: 10.1186/1471-2210-12-3. PubMed PMID: 22553939; PubMed Central PMCID: PMC3403872.

Hill TL, Blikslager AT. Effect of a zinc L-carnosine compound on acid-induced injury in canine gastric mucosa ex vivo. Am J Vet Res. 2012 May;73(5):659-63. doi: 10.2460/ajvr.73.5.659. PubMed PMID: 22533397.

Labens R, Blikslager A. Precision of a photogrammetric method to perform 3D wound measurements compared to standard 2D photographic techniques in the horse. Equine Vet J. 2013 Jan;45(1):41-6. doi: 10.1111/j.2042-3306.2011.00538.x. Epub 2012 Jan 28. PubMed PMID: 22283145.

Meyerhoff RR, Nighot PK, Ali RA, Blikslager AT, Koci MD. Characterization of turkey inducible nitric oxide synthase and identification of its expression in the intestinal epithelium following astrovirus infection. Comp Immunol Microbiol
Infect Dis. 2012 Jan;35(1):63-9. doi: 10.1016/j.cimid.2011.10.001. Epub 2011 Nov 25. PubMed PMID: 22118854; PubMed Central PMCID: PMC3253919.

Nighot PK, Blikslager AT. Chloride channel ClC-2 modulates tight junction barrier function via intracellular trafficking of occludin. Am J Physiol Cell Physiol. 2012 Jan 1;302(1):C178-87. doi: 10.1152/ajpcell.00072.2011. Epub 2011
Sep 28. PubMed PMID: 21956164.

Messenger KM, Papich MG, Blikslager AT. Distribution of enrofloxacin and its active metabolite, using an in vivo ultrafiltration sampling technique after the injection of enrofloxacin to pigs. J Vet Pharmacol Ther. 2012 Oct;35(5):452-9. doi: 10.1111/j.1365-2885.2011.01338.x. Epub 2011 Sep 14. PubMed PMID: 21913941.

Marshall JF, Blikslager AT. The effect of nonsteroidal anti-inflammatory drugs on the equine intestine. Equine Vet J Suppl. 2011 Aug;(39):140-4. doi: 10.1111/j.2042-3306.2011.00398.x. Review. PubMed PMID: 21790769.

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 Suppl. 2011 Aug;(39):106-11. doi: 10.1111/j.2042-3306.2011.00401.x. PubMed PMID: 21790763.

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 Suppl. 2011 Aug;(39):8-15. doi:
10.1111/j.2042-3306.2011.00402.x. PubMed PMID: 21790749.

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 ischemia-injured jejunal mucosa in
horses. Am J Vet Res. 2011 Feb;72(2):226-32. doi: 10.2460/ajvr.72.2.226. PubMed PMID: 21281197.

Davis JL, Marshall JF, Papich MG, Blikslager AT, Campbell NB. The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses. J Vet Pharmacol Ther. 2011 Feb;34(1):12-6. doi: 10.1111/j.1365-2885.2010.01185.x.
PubMed PMID: 21219338.

Blikslager A, Christley R, Jeffcott L, Silver I, van Weeren R. Dr Peter Rossdale, OBE, Editor Equine Veterinary Journal 1980-2010. Equine Vet J. 2011 Jan;43(1):2. doi: 10.1111/j.2042-3306.2010.00347.x. PubMed PMID: 21143626.

Kajino-Sakamoto R, Omori E, Nighot PK, Blikslager AT, Matsumoto K, Ninomiya-Tsuji J. TGF-beta-activated kinase 1 signaling maintains intestinal integrity by preventing accumulation of reactive oxygen species in the intestinal epithelium. J Immunol. 2010 Oct 15;185(8):4729-37. doi: 0.4049/jimmunol.0903587. Epub 2010 Sep 20. PubMed PMID: 20855879; PubMed Central PMCID: PMC3064262.

Schramme M, Hunter S, Campbell N, Blikslager A, Smith R. A surgical tendonitis model in horses: technique, clinical, ultrasonographic and histological characterisation. Vet Comp Orthop Traumatol. 2010;23(4):231-9. doi:
10.3415/VCOT-09-10-0106. Epub 2010 Jun 21. PubMed PMID: 20585715.

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 Jun 15;236(12):1334-7. doi: 10.2460/javma.236.12.1334.
PubMed PMID: 20550449.

Wooten JG, Lascelles BD, Cook VL, Law JM, Blikslager AT. Evaluation of the relationship between lesions in the gastroduodenal region and cyclooxygenase expression in clinically normal dogs. Am J Vet Res. 2010 Jun;71(6):630-5. doi:10.2460/ajvr.71.6.630. PubMed PMID: 20513177.

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 Aug;299(2):G449-56. doi:
10.1152/ajpgi.00520.2009. Epub 2010 May 20. PubMed PMID: 20489043.

Nighot PK, Moeser A, Ali RA, Blikslager AT, Koci MD. Astrovirus infection induces sodium malabsorption and redistributes sodium hydrogen exchanger expression. Virology. 2010 Jun 5;401(2):146-54. doi: 10.1016/j.virol.2010.02.004. Epub 2010 Mar 12. PubMed PMID: 20219227; PubMed Central PMCID: PMC2862094.

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 Jan;42(1):47-52. doi: 10.2746/042516409X456040. PubMed PMID:
20121913.

Morton AJ, Grosche A, Rötting AK, Matyjaszek SA, Blikslager AT, Freeman DE. Expression of cyclooxygenase-1 and -2 in the left dorsal colon after different durations of ischemia and reperfusion in horses. Am J Vet Res. 2009 Dec;70(12):1536-44. doi: 10.2460/ajvr.70.12.1536. PubMed PMID: 19951126.

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
Mar;298(3):G352-63. doi: 10.1152/ajpgi.00081.2009. Epub 2009 Nov 19. PubMed PMID: 19926814; PubMed Central PMCID: PMC2838512.

Cook VL, Jones Shults J, 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
Oct;70(10):1259-68. doi: 10.2460/ajvr.70.10.1259. PubMed PMID: 19795941.

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 Oct;70(10):1243-9. doi: 10.2460/ajvr.70.10.1243. PubMed PMID: 19795939.

Cook VL, Meyer CT, Campbell NB, Blikslager AT. Effect of firocoxib or flunixin meglumine on recovery of ischemic-injured equine jejunum. Am J Vet Res. 2009 Aug;70(8):992-1000. doi: 10.2460/ajvr.70.8.992. PubMed PMID: 19645580.

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 May 15;129(1-2):137-42. doi: 10.1016/j.vetimm.2008.12.017. Epub 2008 Dec 11. PubMed PMID: 19136156.

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 Aug;37(6):558-63. doi: 10.1111/j.1532-950X.2008.00420.x. PubMed PMID: 19134106.

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 Jan 1;315(1):110-8. doi: 10.1016/j.yexcr.2008.10.001. Epub 2008 Oct 17. PubMed PMID: 18976652.

Hess HA, Corl BA, Lin X, Jacobi SK, Harrell RJ, Blikslager AT, Odle J. Enrichment of intestinal mucosal phospholipids with arachidonic and eicosapentaenoic acids fed to suckling piglets is dose and time dependent. J Nutr. 2008 Nov;138(11):2164-71. doi: 10.3945/jn.108.094136. PubMed PMID: 18936214.

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 Oct 21;14(39):6012-7. PubMed PMID: 18932279; PubMed Central PMCID: PMC2760184.

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 Oct;295(4):G791-7. doi:
10.1152/ajpgi.00538.2007. Epub 2008 Aug 21. PubMed PMID: 18719001.

Merritt AM, Blikslager AT. Post operative ileus: to be or not to be? Equine Vet J. 2008 Jun;40(4):295-6. doi: 10.2746/042516408X302537. PubMed PMID: 18672434.

Cook VL, Blikslager AT. Use of systemically administered lidocaine in horses with gastrointestinal tract disease. J Am Vet Med Assoc. 2008 Apr 15;232(8):1144-8. doi: 10.2460/javma.232.8.1144. Review. PubMed PMID: 18412523.

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 Apr;69(4):457-64. doi: 10.2460/ajvr.69.4.457. PubMed PMID: 18380576.

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 Jun;40(4):353-7. doi:
10.2746/042516408X293574. PubMed PMID: 18321812.

Blikslager AT. Life in the gut without oxygen: adaptive mechanisms and inflammatory bowel disease. Gastroenterology. 2008 Jan;134(1):346-8. doi: 10.1053/j.gastro.2007.11.049. PubMed PMID: 18166362.

Corl BA, Odle J, Niu X, Moeser AJ, Gatlin LA, Phillips OT, Blikslager AT, Rhoads JM. Arginine activates intestinal p70(S6k) and protein synthesis in piglet rotavirus enteritis. J Nutr. 2008 Jan;138(1):24-9. PubMed PMID: 18156399.

Tate LP, Blikslager AT, Papich MG. Performance of the 808-nm diode laser on equine upper airway tissue is enhanced by intravenous administration of indocyanine green. Photomed Laser Surg. 2007 Oct;25(5):443-8. PubMed PMID:
17975959.

Moeser AJ, Blikslager AT. Mechanisms of porcine diarrheal disease. J Am Vet Med Assoc. 2007 Jul 1;231(1):56-67. Review. PubMed PMID: 17605665.

Moeser AJ, Blikslager AT, Swanson C. Determination of minimum alveolar concentration of sevoflurane in juvenile swine. Res Vet Sci. 2008 Apr;84(2):283-5. Epub 2007 Jun 13. PubMed PMID: 17570452.

Little D, Jones SL, Blikslager AT. Cyclooxygenase (COX) inhibitors and the intestine. J Vet Intern Med. 2007 May-Jun;21(3):367-77. Review. PubMed PMID: 17552439.

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(6):614-24. PubMed PMID: 17542694.

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 Gastrointest Liver Physiol. 2007 Aug;293(2):G413-21. Epub 2007 May 24. PubMed PMID: 17525151.

Blikslager AT, Moeser AJ, Gookin JL, Jones SL, Odle J. Restoration of barrier function in injured intestinal mucosa. Physiol Rev. 2007 Apr;87(2):545-64. Review. PubMed PMID: 17429041.

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 Feb;30(1):43-8. PubMed PMID: 17217400.

Elce YA, Orsini JA, Blikslager AT. Expression of cyclooxygenase-1 and -2 in naturally occurring squamous cell carcinomas in horses. Am J Vet Res. 2007 Jan;68(1):76-80. PubMed PMID: 17199422.

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.

Contact Us

Please contact the PI regarding training and funding opportunities.

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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