Diarrhea; Electrophysiology; Gastric Acid; Gastroenterology; Physiology
Our primary focus is on real time monitoring of ion transport mechanisms in epithelia, using high-resolution microscopy. One of the crucial problems facing all epithelial cells is the control of the intracellular milieu. In an effort to maintain ionic homeostasis, epithelial cells have devised a variety of ion channels, transport proteins, and carriers to regulate and maintain the intracellular ionic concentrations. To further understand how ions are transported in epithelial cells, we have developed a variety of optical techniques to continuously monitor intracellular ionic concentrations in real time. Using high-resolution video or confocal microscopy we are presently able to monitor intracellular Ca2+, Na+, K+, Cl-, pH, and membrane potential. We are currently investigating various aspects of renal tubule and gastric tissue ion transport in intact renal tubules and gastric glands. We also are characterizing the secretory and reabsorptive properties of the colonic crypt, with a special focus on diarrheal disease.
Specialized Terms: Gastric Acid Secretion; Colonic Fluid Transport; Renal Physiology; Intracellular Ion Activity Measurements; Calcium Sensing Receptor; Diarrheal disease; electrophysiology; CFTR; AMPKinase volume regulation
Extensive Research Description
We are focused on 3 main areas; gastric ion transport in health and disease, intestinal ion transport in health and disease, and renal physiology. For gastric ion transport we are focusing on means to modulate acid secretion and reverse erosion. We use a combination of natural products and biochemical modifications to treat acid disease at the cellular level. For studies of intestinal ion transport, we are focusing on how the calcium sensing receptor(CaSR) can modulate fluid transport during toxin induced diarrhea. In addition we are investigating means to prevent ischemic injury by activating ionic pathways using the AMPKinase. Finally we are trying to prevent IBD/IBS associated epithelial injury in the gut by Casr activation . For the renal studies we are interested in acid base homeostasis along the nephron, and are now investigating the role of the CaSR in modulating fluid secretion and renal stone formation.
Effect of NSAIDs on Na+/H+ exchanger activity in Rat colonic crypts
Roginiel AC, Kohut DL, Kaur S, Saleh AM, Weber T, Geibel P, Singh H, and Geibel JP. Effect of NSAIDs on Na+/H+ exchanger activity in Rat colonic crypts. American journal of physiology Cell physiology 2013
Gastric acid, calcium absorption, and their impact on bone health.
Kopic S, and Geibel JP. Gastric acid, calcium absorption, and their impact on bone health. Physiological reviews 93: 189-268, 2013.
The calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule
Capasso G, Geibel PJ, Damiano S, Jaeger P, Richards WG, and Geibel JP. The calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule. Kidney international 2013.
Vacuolar-type H+-ATPase-mediated proton transport in the rat parietal cell.
Kopic S, Wagner ME, Griessenauer C, Socrates T, Ritter M, and Geibel JP. Vacuolar-type H+-ATPase-mediated proton transport in the rat parietal cell. Pflugers Archive : European journal of physiology 463: 419-427, 2012.
Functional role of NHE4 as a pH regulator in rat and human colonic crypts
Arena EA, Longo WE, Roberts KE, Geibel P, Nateqi J, Brandstetter M, and Geibel JP. Functional role of NHE4 as a pH regulator in rat and human colonic crypts. American journal of physiology Cell physiology 302: C412-418, 2012
Zinc salts provide a novel, prolonged and rapid inhibition of gastric acid secretion
Kirchhoff P, Socrates T, Sidani S, Duffy A, Breidthardt T, Grob C, Viehl CT, Beglinger C, Oertli D, and Geibel JP. Zinc salts provide a novel, prolonged and rapid inhibition of gastric acid secretion. The American journal of gastroenterology 106: 62-70, 2011.
Full List of PubMed Publications
- AlKukhun A, Caturegli G, Munoz-Abraham AS, Judeeba S, Patron-Lozano R, Morotti R, Rodriguez-Davalos MI, Geibel JP: Use of Fluorescein Isothiocyanate-Inulin as a Marker for Intestinal Ischemic Injury. J Am Coll Surg. 2016 Dec 23; 2016 Dec 23. PMID: 28017811
- Munoz-Abraham AS, Judeeba S, Alkukhun A, Alfadda T, Patron-Lozano R, Rodriguez-Davalos MI, Geibel JP: A new method to measure intestinal secretion using fluorescein isothiocyanate-inulin in small bowel of rats. J Surg Res. 2015 Aug; 2015 Apr 20. PMID: 25976849
- Vucic E, Alfadda T, MacGregor GG, Dong K, Wang T, Geibel JP: Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1. Pflugers Arch. 2015 Jul; 2014 Aug 17. PMID: 25127675
- McNeer NA, Anandalingam K, Fields RJ, Caputo C, Kopic S, Gupta A, Quijano E, Polikoff L, Kong Y, Bahal R, Geibel JP, Glazer PM, Saltzman WM, Egan ME: Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium. Nat Commun. 2015 Apr 27; 2015 Apr 27. PMID: 25914116
- Alfadda TI, Saleh AM, Houillier P, Geibel JP: Calcium-sensing receptor 20 years later. Am J Physiol Cell Physiol. 2014 Aug 1; 2014 May 28. PMID: 24871857
- Collaco AM, Geibel P, Lee BS, Geibel JP, Ameen NA: Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR. Am J Physiol Cell Physiol. 2013 Nov 1; 2013 Aug 28. PMID: 23986201
- Roginiel AC, Kohut DL, Kaur S, Saleh AM, Weber T, Geibel P, Singh H, Geibel JP: Effect of NSAIDs on Na⁺/H⁺ exchanger activity in rat colonic crypts. Am J Physiol Cell Physiol. 2013 Sep; 2013 Jun 5. PMID: 23739181
- Barmeyer C, Ye JH, Soroka C, Geibel P, Hingsammer LM, Weitgasser L, Atway D, Geibel JP, Binder HJ, Rajendran VM: Identification of functionally distinct Na-HCO3 co-transporters in colon. PLoS One. 2013; 2013 May 14. PMID: 23690961
- Kopic S, Geibel JP: Gastric acid, calcium absorption, and their impact on bone health. Physiol Rev. 2013 Jan. PMID: 23303909
- Kopic S, Wagner ME, Griessenauer C, Socrates T, Ritter M, Geibel JP: Vacuolar-type H+-ATPase-mediated proton transport in the rat parietal cell. Pflugers Arch. 2012 Mar; 2011 Nov 17. PMID: 22146938
- Arena EA, Longo WE, Roberts KE, Geibel P, Nateqi J, Brandstetter M, Geibel JP: Functional role of NHE4 as a pH regulator in rat and human colonic crypts. Am J Physiol Cell Physiol. 2012 Jan 15; 2011 Nov 2. PMID: 22049213
- Shenoy A, Kopic S, Murek M, Caputo C, Geibel JP, Egan ME: Calcium-modulated chloride pathways contribute to chloride flux in murine cystic fibrosis-affected macrophages. Pediatr Res. 2011 Nov. PMID: 21796019
- Kirchhoff P, Socrates T, Sidani S, Duffy A, Breidthardt T, Grob C, Viehl CT, Beglinger C, Oertli D, Geibel JP: Zinc salts provide a novel, prolonged and rapid inhibition of gastric acid secretion. Am J Gastroenterol. 2011 Jan; 2010 Aug 24. PMID: 20736941
- Wagner CA, Mohebbi N, Uhlig U, Giebisch GH, Breton S, Brown D, Geibel JP: Angiotensin II stimulates H⁺-ATPase activity in intercalated cells from isolated mouse connecting tubules and cortical collecting ducts. Cell Physiol Biochem. 2011; 2011 Nov 18. PMID: 22116365
- Kopic S, Geibel JP: Update on the mechanisms of gastric acid secretion. Curr Gastroenterol Rep. 2010 Dec. PMID: 20821079
- Geibel JP: The calcium-sensing receptor. J Nephrol. 2010 Nov-Dec. PMID: 21170870
- Kopic S, Geibel JP: Toxin mediated diarrhea in the 21 century: the pathophysiology of intestinal ion transport in the course of ETEC, V. cholerae and rotavirus infection. Toxins (Basel). 2010 Aug; 2010 Aug 10. PMID: 22069677
- Kopic S, Murek M, Geibel JP: Revisiting the parietal cell. Am J Physiol Cell Physiol. 2010 Jan; 2009 Nov 4. PMID: 19889964
- Kopic S, Corradini S, Sidani S, Murek M, Vardanyan A, Föller M, Ritter M, Geibel JP: Ethanol inhibits gastric acid secretion in rats through increased AMP-kinase activity. Cell Physiol Biochem. 2010; 2010 Jan 12. PMID: 20110680
- Sidani S, Kopic S, Socrates T, Kirchhoff P, Föller M, Murek M, Capasso A, Geibel JP: AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion. Pflugers Arch. 2009 Nov; 2009 Jul 21. PMID: 19621238
- Geibel JP, Hebert SC: The functions and roles of the extracellular Ca2+-sensing receptor along the gastrointestinal tract. Annu Rev Physiol. 2009. PMID: 19575679
- Kosiek O, Busque SM, Föller M, Shcheynikov N, Kirchhoff P, Bleich M, Muallem S, Geibel JP: SLC26A7 can function as a chloride-loading mechanism in parietal cells. Pflugers Arch. 2007 Sep; 2007 Apr 3. PMID: 17404755
- Sidani SM, Kirchhoff P, Socrates T, Stelter L, Ferreira E, Caputo C, Roberts KE, Bell RL, Egan ME, Geibel JP: DeltaF508 mutation results in impaired gastric acid secretion. J Biol Chem. 2007 Mar 2; 2006 Dec 18. PMID: 17178714
- Lang PA, Schniepp R, Kirchhoff P, Socrates T, Sidani SM, Geibel JP: PI3 kinase dependent stimulation of gastric acid secretion by dexamethasone. Cell Physiol Biochem. 2007. PMID: 17762179
- Busque SM, Kerstetter JE, Geibel JP, Insogna K: L-type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells. Am J Physiol Gastrointest Liver Physiol. 2005 Oct; 2005 Jun 16. PMID: 15961860
- Finberg KE, Wagner CA, Bailey MA, Paunescu TG, Breton S, Brown D, Giebisch G, Geibel JP, Lifton RP: The B1-subunit of the H(+) ATPase is required for maximal urinary acidification. Proc Natl Acad Sci U S A. 2005 Sep 20; 2005 Sep 8. PMID: 16174750
- Geibel JP: Role of potassium in acid secretion. World J Gastroenterol. 2005 Sep 14. PMID: 16149129
- Binder HJ, Rajendran V, Sadasivan V, Geibel JP: Bicarbonate secretion: a neglected aspect of colonic ion transport. J Clin Gastroenterol. 2005 Apr. PMID: 15758660
- Hoffman JF, Geibel JP: Fluorescent imaging of Cl- in Amphiuma red blood cells: how the nuclear exclusion of Cl- affects the plasma membrane potential. Proc Natl Acad Sci U S A. 2005 Jan 18; 2005 Jan 6. PMID: 15637151
- Geibel JP: Secretion and absorption by colonic crypts. Annu Rev Physiol. 2005. PMID: 15709966
- Eisenberg ML, Maker AV, Slezak LA, Nathan JD, Sritharan KC, Jena BP, Geibel JP, Andersen DK: Insulin receptor (IR) and glucose transporter 2 (GLUT2) proteins form a complex on the rat hepatocyte membrane. Cell Physiol Biochem. 2005. PMID: 15665515
- Cheng SX, Geibel JP, Hebert SC: Extracellular polyamines regulate fluid secretion in rat colonic crypts via the extracellular calcium-sensing receptor. Gastroenterology. 2004 Jan. PMID: 14699496
- Kirchhoff P, Wagner CA, Gaetzschmann F, Radebold K, Geibel JP: Demonstration of a functional apical sodium hydrogen exchanger in isolated rat gastric glands. Am J Physiol Gastrointest Liver Physiol. 2003 Dec; 2003 Aug 7. PMID: 12907430
- Stehberger PA, Schulz N, Finberg KE, Karet FE, Giebisch G, Lifton RP, Geibel JP, Wagner CA: Localization and regulation of the ATP6V0A4 (a4) vacuolar H+-ATPase subunit defective in an inherited form of distal renal tubular acidosis. J Am Soc Nephrol. 2003 Dec. PMID: 14638902
- Finberg KE, Wagner CA, Stehberger PA, Geibel JP, Lifton RP: Molecular cloning and characterization of Atp6v1b1, the murine vacuolar H+ -ATPase B1-subunit. Gene. 2003 Oct 30. PMID: 14585495
- Wagner CA, Finberg KE, Stehberger PA, Lifton RP, Giebisch GH, Aronson PS, Geibel JP: Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status. Kidney Int. 2002 Dec. PMID: 12427135
- Cheng SX, Okuda M, Hall AE, Geibel JP, Hebert SC: Expression of calcium-sensing receptor in rat colonic epithelium: evidence for modulation of fluid secretion. Am J Physiol Gastrointest Liver Physiol. 2002 Jul. PMID: 12065312
- Sangan P, Rajendran VM, Geibel JP, Binder HJ: Cloning and expression of a chloride-dependent Na+-H+ exchanger. J Biol Chem. 2002 Mar 22; 2001 Dec 28. PMID: 11773056
- Geibel JP: Microscopy as a tool for renal research. J Nephrol. 2002 Mar-Apr. PMID: 12027215
- Wagner CA, Geibel JP: Acid-base transport in the collecting duct. J Nephrol. 2002 Mar-Apr. PMID: 12027210