Contact Us

  • Gary E Shull, PhD
  • Professor of Molecular Genetics
  • Phone: 513-558-0056
  • Email: gary.shull@uc.edu

    Research Interests:

  • I have a long-term interest in the mechanisms of ion transport and the physiological and pathophysiological processes involving various ion transporters. Our earlier efforts were directed toward 1) identification of P-type ATPases, such as Na,K-ATPases, H,K-ATPases, P5-ATPases, and the PMCA, SERCA, and SPCA Ca pumps, and 2) identification of ion transporters that mediate transepithelial ion fluxes, which involves extensive coupling of HCO3 and H transporters, including H pumps, Cl/HCO3 exchangers, Na/H exchangers, and Na/HCO3 cotransporters. To develop a comprehensive understanding of the physiological functions of these transporters in epithelial tissues, we began developing and analyzing knockout mouse models. These studies have led to important insights regarding the concerted actions of ion transporters on both apical and basolateral membranes of epithelial tissues, revealed major effects on systemic acid-base and electrolyte homeostasis, and contributed to an understanding of their roles in a number of renal, gastrointestinal, and skin diseases. Surprisingly, many of the transporters involved in transepithelial ion fluxes are also expressed in heart, with Cl/HCO3 exchangers and Na-coupled acid-base transporters being particularly abundant. The most logical explanation for their prevalence in heart is that they affect pHi and Na concentrations in subsarcolemmal spaces and other localized regions of the cell, with subsequent effects on Ca handling and other processes, including major effects on metabolism and, most surprisingly, rapid effects on signaling via the cytoskeleton and associated proteins. Our data show that loss of a number of these transporters is well tolerated by the heart, but has unexpected and dramatic effects (both positive and negative) on responses to disease conditions, cardiac performance under certain conditions, and metabolism. These studies are contributing to a better understanding of the cellular and physiological functions of these ion transporters, a number of which serve as important drug receptors, and this in turn is leading to a better understanding of their roles in human disease.

    Education/Credentials:

  • PhD: North Carolina State University, 1983

Post Graduate Training/Education:

  • Post-doctoral assistant
    03/01/1983-08/31/1986, University of Cincinnati College of Medicine, Cincinnati, Ohio, Postdoctoral studies on cloning of the Na,K-ATPase alpha and beta subunits

Peer Reviewed Publications (in chronological order):

  • Soleimani, M., Barone, S., Xu, J., Shull, G. E., Siddiqui, F., Zahedi, K., & Amlal, H. (2012). Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure. . Proceedings of the National Academy of Sciences of the United States of America , 109 (33) , 13368-73.
  • Chen, M., Praetorius, J., Zheng, W., Xiao, F., Riederer, B., Singh, A. K., Stieger, N., Wang, J., Shull, G. E., Aalkjaer, C., & Seidler, U. (2012). The electroneutral Na?:HCO?? cotransporter NBCn1 is a major pHi regulator in murine duodenum. . The Journal of Physiology , 590 (Pt 14) , 3317-33.
  • Pan, W., Borovac, J., Spicer, Z., Hoenderop, J. G., Bindels, R. J., Shull, G. E., Doschak, M. R., Cordat, E., & Alexander, R. T. (2012). The epithelial sodium/proton exchanger, NHE3, is necessary for renal and intestinal calcium (re)absorption. . American Journal of Physiology. Renal Physiology , 302 (8) , F943-56.
  • Ruminot, I., Gutiérrez, R., Peña-Münzenmayer, G., Añazco, C., Sotelo-Hitschfeld, T., Lerchundi, R., Niemeyer, M. I., Shull, G. E., & Barros, L. F. (2011). NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K+. . The Journal of Neuroscience : the Official Journal of the Society For Neuroscience , 31 (40) , 14264-71.
  • Miller, M. L., Andringa, A., Schultheis, P. J., & Shull, G. E. (2011). Loss of the NHE2 Na+/H+ exchanger in mice results in dilation of folliculo-stellate cell canaliculi. . Journal of Biomedicine & Biotechnology , 2011 , 510827.
  • Al Moamen, N. J., Prasad, V., Bodi, I., Miller, M. L., Neiman, M. L., Lasko, V. M., Alper, S. L., Wieczorek, D. F., Lorenz, J. N., & Shull, G. E. (2011). Loss of the AE3 anion exchanger in a hypertrophic cardiomyopathy model causes rapid decompensation and heart failure. . Journal of Molecular and Cellular Cardiology , 50 (1) , 137-46.
  • Shao, J., Gumz, M. L., Cain, B. D., Xia, S., Shull, G. E., van Driel, I. R., & Wingo, C. S. (2010). Pharmacological profiles of the murine gastric and colonic H,K-ATPases. . Biochimica Et Biophysica Acta , 1800 (9) , 906-11.
  • Liu, Y., Kintner, D. B., Begum, G., Algharabli, J., Cengiz, P., Shull, G. E., Liu, X., & Sun, D. (2010). Endoplasmic reticulum Ca2+ signaling and mitochondrial Cyt c release in astrocytes following oxygen and glucose deprivation. . Journal of Neurochemistry , 114 (5) , 1436-46.
  • Bradford, E. M., Miller, M. L., Prasad, V., Nieman, M. L., Gawenis, L. R., Berryman, M., Lorenz, J. N., Tso, P., & Shull, G. E. (2010). CLIC5 mutant mice are resistant to diet-induced obesity and exhibit gastric hemorrhaging and increased susceptibility to torpor. . American Journal of Physiology. Regulatory, Integrative and Comparative Physiology , 298 (6) , R1531-42.
  • Bourgeois, S., Meer, L. V., Wootla, B., Bloch-Faure, M., Chambrey, R., Shull, G. E., Gawenis, L. R., & Houillier, P. (2010). NHE4 is critical for the renal handling of ammonia in rodents. . The Journal of Clinical Investigation , 120 (6) , 1895-904.
  • Leviel, F., Hübner, C. A., Houillier, P., Morla, L., El Moghrabi, S., Brideau, G., Hassan, H., Hatim, H., Parker, M. D., Kurth, I., Kougioumtzes, A., Sinning, A., Pech, V., Riemondy, K. A., Miller, R. L., Hummler, E., Shull, G. E., Aronson, P. S., Doucet, A., Wall, S. M., Chambrey, R., & Eladari, D. (2010). The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. . The Journal of Clinical Investigation , 120 (5) , 1627-35.
  • Gawenis, L. R., Bradford, E. M., Alper, S. L., Prasad, V., & Shull, G. E. (2010). AE2 Cl-/HCO3- exchanger is required for normal cAMP-stimulated anion secretion in murine proximal colon. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 298 (4) , G493-503.
  • Miller, M. L., Andringa, A., Zavros, Y., Bradford, E. M., & Shull, G. E. (2010). Volume density, distribution, and ultrastructure of secretory and basolateral membranes and mitochondria predict parietal cell secretory (dys)function. . Journal of Biomedicine & Biotechnology , 2010 , 394198.
  • Chen, X., Kintner, D. B., Baba, A., Matsuda, T., Shull, G. E., & Sun, D. (2010). Protein aggregation in neurons following OGD: a role for Na+ and Ca2+ ionic dysregulation. . Journal of Neurochemistry , 112 (1) , 173-82.
  • Sinkins, W. G., Estacion, M., Prasad, V., Goel, M., Shull, G. E., Kunze, D. L., & Schilling, W. P. (2009). Maitotoxin converts the plasmalemmal Ca(2+) pump into a Ca(2+)-permeable nonselective cation channel. . American Journal of Physiology. Cell Physiology , 297 (6) , C1533-43.
  • Yu, H., Riederer, B., Stieger, N., Boron, W. F., Shull, G. E., Manns, M. P., Seidler, U. E., & Bachmann, O. (2009). Secretagogue stimulation enhances NBCe1 (electrogenic Na(+)/HCO(3)(-) cotransporter) surface expression in murine colonic crypts. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 297 (6) , G1223-31.
  • Bradford, E. M., Sartor, M. A., Gawenis, L. R., Clarke, L. L., & Shull, G. E. (2009). Reduced NHE3-mediated Na+ absorption increases survival and decreases the incidence of intestinal obstructions in cystic fibrosis mice. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 296 (4) , G886-98.
  • Wu, X., Chang, B., Blair, N. S., Sargent, M., York, A. J., Robbins, J., Shull, G. E., & Molkentin, J. D. (2009). Plasma membrane Ca2+-ATPase isoform 4 antagonizes cardiac hypertrophy in association with calcineurin inhibition in rodents. . The Journal of Clinical Investigation , 119 (4) , 976-85.
  • Xu, J., Song, P., Miller, M. L., Borgese, F., Barone, S., Riederer, B., Wang, Z., Alper, S. L., Forte, J. G., Shull, G. E., Ehrenfeld, J., Seidler, U., & Soleimani, M. (2008). Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach. . Proceedings of the National Academy of Sciences of the United States of America , 105 (46) , 17955-60.
  • Prasad, V., Bodi, I., Meyer, J. W., Wang, Y., Ashraf, M., Engle, S. J., Doetschman, T., Sisco, K., Nieman, M. L., Miller, M. L., Lorenz, J. N., & Shull, G. E. (2008). Impaired cardiac contractility in mice lacking both the AE3 Cl-/HCO3- exchanger and the NKCC1 Na+-K+-2Cl- cotransporter: effects on Ca2+ handling and protein phosphatases. . The Journal of Biological Chemistry , 283 (46) , 31303-14.
  • Hanner, F., Chambrey, R., Bourgeois, S., Meer, E., Mucsi, I., Rosivall, L., Shull, G. E., Lorenz, J. N., Eladari, D., & Peti-Peterdi, J. (2008). Increased renal renin content in mice lacking the Na+/H+ exchanger NHE2. . American Journal of Physiology. Renal Physiology , 294 (4) , F937-44.
  • Luo, J., Wang, Y., Chen, H., Kintner, D. B., Cramer, S. W., Gerdts, J. K., Chen, X., Shull, G. E., Philipson, K. D., & Sun, D. (2008). A concerted role of Na+ -K+ -Cl- cotransporter and Na+/Ca2+ exchanger in ischemic damage. . Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism , 28 (4) , 737-46.
  • Lynch, I. J., Rudin, A., Xia, S., Stow, L. R., Shull, G. E., Weiner, I. D., Cain, B. D., & Wingo, C. S. (2008). Impaired acid secretion in cortical collecting duct intercalated cells from H-K-ATPase-deficient mice: role of HKalpha isoforms. . American Journal of Physiology. Renal Physiology , 294 (3) , F621-7.
  • Diaz, R. C., Vazquez, A. E., Dou, H., Wei, D., Cardell, E. L., Lingrel, J., Shull, G. E., Doyle, K. J., & Yamoah, E. N. (2007). Conservation of hearing by simultaneous mutation of Na,K-ATPase and NKCC1. . Journal of the Association For Research in Otolaryngology : JARO , 8 (4) , 422-34.
  • Luo, J., Kintner, D. B., Shull, G. E., & Sun, D. (2007). ERK1/2-p90RSK-mediated phosphorylation of Na+/H+ exchanger isoform 1. A role in ischemic neuronal death. . The Journal of Biological Chemistry , 282 (38) , 28274-84.
  • Okunade, G. W., Miller, M. L., Azhar, M., Andringa, A., Sanford, L. P., Doetschman, T., Prasad, V., & Shull, G. E. (2007). Loss of the Atp2c1 secretory pathway Ca(2+)-ATPase (SPCA1) in mice causes Golgi stress, apoptosis, and midgestational death in homozygous embryos and squamous cell tumors in adult heterozygotes. . The Journal of Biological Chemistry , 282 (36) , 26517-27.
  • Alvarez, B. V., Gilmour, G. S., Mema, S. C., Martin, B. T., Shull, G. E., Casey, J. R., & Sauvé, Y. (2007). Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger. . PloS One , 2 (9) , e839.
  • Simpson, J. E., Schweinfest, C. W., Shull, G. E., Gawenis, L. R., Walker, N. M., Boyle, K. T., Soleimani, M., & Clarke, L. L. (2007). PAT-1 (Slc26a6) is the predominant apical membrane Cl-/HCO3- exchanger in the upper villous epithelium of the murine duodenum. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 292 (4) , G1079-88.
  • Gawenis, L. R., Bradford, E. M., Prasad, V., Lorenz, J. N., Simpson, J. E., Clarke, L. L., Woo, A. L., Grisham, C., Sanford, L. P., Doetschman, T., Miller, M. L., & Shull, G. E. (2007). Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. . The Journal of Biological Chemistry , 282 (12) , 9042-52.
  • Kintner, D. B., Luo, J., Gerdts, J., Ballard, A. J., Shull, G. E., & Sun, D. (2007). Role of Na+-K+-Cl- cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction in astrocytes following in vitro ischemia. . American Journal of Physiology. Cell Physiology , 292 (3) , C1113-22.
  • Luo, J., Wang, Y., Chen, X., Chen, H., Kintner, D. B., Shull, G. E., Philipson, K. D., & Sun, D. (2007). Increased tolerance to ischemic neuronal damage by knockdown of Na+-Ca2+ exchanger isoform 1. . Annals of the New York Academy of Sciences , 1099 , 292-305.
  • Prasad, V., Okunade, G., Liu, L., Paul, R. J., & Shull, G. E. (2007). Distinct phenotypes among plasma membrane Ca2+-ATPase knockout mice. . Annals of the New York Academy of Sciences , 1099 , 276-86.
  • Ficarella, R., Di Leva, F., Bortolozzi, M., Ortolano, S., Donaudy, F., Petrillo, M., Melchionda, S., Lelli, A., Domi, T., Fedrizzi, L., Lim, D., Shull, G. E., Gasparini, P., Brini, M., Mammano, F., & Carafoli, E. (2007). A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness. . Proceedings of the National Academy of Sciences of the United States of America , 104 (5) , 1516-21.
  • Liu, L., Ishida, Y., Okunade, G., Pyne-Geithman, G. J., Shull, G. E., & Paul, R. J. (2007). Distinct roles of PMCA isoforms in Ca2+ homeostasis of bladder smooth muscle: evidence from PMCA gene-ablated mice. . American Journal of Physiology. Cell Physiology , 292 (1) , C423-31.
  • Guan, Y., Dong, J., Tackett, L., Meyer, J. W., Shull, G. E., & Montrose, M. H. (2006). NHE2 is the main apical NHE in mouse colonic crypts but an alternative Na+-dependent acid extrusion mechanism is upregulated in NHE2-null mice. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 291 (4) , G689-99.
  • Lorenz, J. N., Dostanic-Larson, I., Shull, G. E., & Lingrel, J. B. (2006). Ouabain inhibits tubuloglomerular feedback in mutant mice with ouabain-sensitive alpha1 Na,K-ATPase. . Journal of the American Society of Nephrology : JASN , 17 (9) , 2457-63.
  • Pestov, N. B., Korneenko, T. V., Shakhparonov, M. I., Shull, G. E., & Modyanov, N. N. (2006). Loss of acidification of anterior prostate fluids in Atp12a-null mutant mice indicates that nongastric H-K-ATPase functions as proton pump in vivo. . American Journal of Physiology. Cell Physiology , 291 (2) , C366-74.
  • Liu, L., Ishida, Y., Okunade, G., Shull, G. E., & Paul, R. J. (2006). Role of plasma membrane Ca2+-ATPase in contraction-relaxation processes of the bladder: evidence from PMCA gene-ablated mice. . American Journal of Physiology. Cell Physiology , 290 (4) , C1239-47.
  • Wall, S. M., Knepper, M. A., Hassell, K. A., Fischer, M. P., Shodeinde, A., Shin, W., Pham, T. D., Meyer, J. W., Lorenz, J. N., Beierwaltes, W. H., Dietz, J. R., Shull, G. E., & Kim, Y. (2006). Hypotension in NKCC1 null mice: role of the kidneys. . American Journal of Physiology. Renal Physiology , 290 (2) , F409-16.
  • Luo, J., Chen, H., Kintner, D. B., Shull, G. E., & Sun, D. (2006). Inhibition of Na+/H+ exchanger isoform 1 attenuates mitochondrial cytochrome C release in cortical neurons following in vitro ischemia. . Acta Neurochirurgica. Supplement , 96 , 244-8.
  • Luo, J., Chen, H., Kintner, D. B., Shull, G. E., & Sun, D. (2005). Decreased neuronal death in Na+/H+ exchanger isoform 1-null mice after in vitro and in vivo ischemia. . The Journal of Neuroscience : the Official Journal of the Society For Neuroscience , 25 (49) , 11256-68.
  • Hunt, D. L., King, B., Kahn, D. M., Yamoah, E. N., Shull, G. E., & Krubitzer, L. (2005). Aberrant retinal projections in congenitally deaf mice: how are phenotypic characteristics specified in development and evolution? . The Anatomical Record. Part A, Discoveries in Molecular, Cellular, and Evolutionary Biology , 287 (1) , 1051-66.
  • Kintner, D. B., Look, A., Shull, G. E., & Sun, D. (2005). Stimulation of astrocyte Na+/H+ exchange activity in response to in vitro ischemia depends in part on activation of ERK1/2. . American Journal of Physiology. Cell Physiology , 289 (4) , C934-45.
  • Prasad, V., Boivin, G. P., Miller, M. L., Liu, L. H., Erwin, C. R., Warner, B. W., & Shull, G. E. (2005). Haploinsufficiency of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 Ca2+ pump, predisposes mice to squamous cell tumors via a novel mode of cancer susceptibility. . Cancer Research , 65 (19) , 8655-61.
  • Xu, J., Henriksnäs, J., Barone, S., Witte, D., Shull, G. E., Forte, J. G., Holm, L., & Soleimani, M. (2005). SLC26A9 is expressed in gastric surface epithelial cells, mediates Cl-/HCO3- exchange, and is inhibited by NH4+. . American Journal of Physiology. Cell Physiology , 289 (2) , C493-505.
  • Judd, L. M., Andringa, A., Rubio, C. A., Spicer, Z., Shull, G. E., & Miller, M. L. (2005). Gastric achlorhydria in H/K-ATPase-deficient (Atp4a(-/-)) mice causes severe hyperplasia, mucocystic metaplasia and upregulation of growth factors. . Journal of Gastroenterology and Hepatology , 20 (8) , 1266-78.
  • Nicolet-Barousse, L., Blanchard, A., Roux, C., Pietri, L., Bloch-Faure, M., Kolta, S., Chappard, C., Geoffroy, V., Morieux, C., Jeunemaitre, X., Shull, G. E., Meneton, P., Paillard, M., Houillier, P., & De Vernejoul, M. (2005). Inactivation of the Na-Cl co-transporter (NCC) gene is associated with high BMD through both renal and bone mechanisms: analysis of patients with Gitelman syndrome and Ncc null mice. . Journal of Bone and Mineral Research : the Official Journal of the American Society For Bone and Mineral Research , 20 (5) , 799-808.
  • Gawenis, L. R., Greeb, J. M., Prasad, V., Grisham, C., Sanford, L. P., Doetschman, T., Andringa, A., Miller, M. L., & Shull, G. E. (2005). Impaired gastric acid secretion in mice with a targeted disruption of the NHE4 Na+/H+ exchanger. . The Journal of Biological Chemistry , 280 (13) , 12781-9.
  • Ramos-Castañeda, J., Park, Y., Liu, M., Hauser, K., Rudolph, H., Shull, G. E., Jonkman, M. F., Mori, K., Ikeda, S., Ogawa, H., & Arvan, P. (2005). Deficiency of ATP2C1, a Golgi ion pump, induces secretory pathway defects in endoplasmic reticulum (ER)-associated degradation and sensitivity to ER stress. . The Journal of Biological Chemistry , 280 (10) , 9467-73.
  • Noonan, W. T., Woo, A. L., Nieman, M. L., Prasad, V., Schultheis, P. J., Shull, G. E., & Lorenz, J. N. (2005). Blood pressure maintenance in NHE3-deficient mice with transgenic expression of NHE3 in small intestine. . American Journal of Physiology. Regulatory, Integrative and Comparative Physiology , 288 (3) , R685-91.
  • Kurnellas, M. P., Nicot, A., Shull, G. E., & Elkabes, S. (2005). Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal cord: a potential mechanism for neurodegeneration in multiple sclerosis and spinal cord injury. . FASEB Journal : Official Publication of the Federation of American Societies For Experimental Biology , 19 (2) , 298-300.
  • Xu, Y., Zhang, Z., Timofeyev, V., Sharma, D., Xu, D., Tuteja, D., Dong, P. H., Ahmmed, G. U., Ji, Y., Shull, G. E., Periasamy, M., & Chiamvimonvat, N. (2005). The effects of intracellular Ca2+ on cardiac K+ channel expression and activity: novel insights from genetically altered mice. . The Journal of Physiology , 562 (Pt 3) , 745-58.
  • Chen, H., Luo, J., Kintner, D. B., Shull, G. E., & Sun, D. (2005). Na(+)-dependent chloride transporter (NKCC1)-null mice exhibit less gray and white matter damage after focal cerebral ischemia. . Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism , 25 (1) , 54-66.
  • Bailey, M. A., Giebisch, G., Abbiati, T., Aronson, P. S., Gawenis, L. R., Shull, G. E., & Wang, T. (2004). NHE2-mediated bicarbonate reabsorption in the distal tubule of NHE3 null mice. . The Journal of Physiology , 561 (Pt 3) , 765-75.
  • Gawenis, L. R., Hut, H., Bot, A. G. M., Shull, G. E., de Jonge, H. R., Stien, X., Miller, M. L., & Clarke, L. L. (2004). Electroneutral sodium absorption and electrogenic anion secretion across murine small intestine are regulated in parallel. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 287 (6) , G1140-9.
  • Good, D. W., Watts, B. A., George, T., Meyer, J. W., & Shull, G. E. (2004). Transepithelial HCO3- absorption is defective in renal thick ascending limbs from Na+/H+ exchanger NHE1 null mutant mice. . American Journal of Physiology. Renal Physiology , 287 (6) , F1244-9.
  • Lenart, B., Kintner, D. B., Shull, G. E., & Sun, D. (2004). Na-K-Cl cotransporter-mediated intracellular Na+ accumulation affects Ca2+ signaling in astrocytes in an in vitro ischemic model. . The Journal of Neuroscience : the Official Journal of the Society For Neuroscience , 24 (43) , 9585-97.
  • Schultheis, P. J., Hagen, T. T., O'Toole, K. K., Tachibana, A., Burke, C. R., McGill, D. L., Okunade, G. W., & Shull, G. E. (2004). Characterization of the P5 subfamily of P-type transport ATPases in mice. . Biochemical and Biophysical Research Communications , 323 (3) , 731-8.
  • Reinhardt, T. A., Lippolis, J. D., Shull, G. E., & Horst, R. L. (2004). Null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2 impairs calcium transport into milk. . The Journal of Biological Chemistry , 279 (41) , 42369-73.
  • Prasad, V., Okunade, G. W., Miller, M. L., & Shull, G. E. (2004). Phenotypes of SERCA and PMCA knockout mice. . Biochemical and Biophysical Research Communications , 322 (4) , 1192-203.
  • Gekle, M., Völker, K., Mildenberger, S., Freudinger, R., Shull, G. E., & Wiemann, M. (2004). NHE3 Na+/H+ exchanger supports proximal tubular protein reabsorption in vivo. . American Journal of Physiology. Renal Physiology , 287 (3) , F469-73.
  • Loffing, J., Vallon, V., Loffing-Cueni, D., Aregger, F., Richter, K., Pietri, L., Bloch-Faure, M., Hoenderop, J. G. J., Shull, G. E., Meneton, P., & Kaissling, B. (2004). Altered renal distal tubule structure and renal Na(+) and Ca(2+) handling in a mouse model for Gitelman's syndrome. . Journal of the American Society of Nephrology : JASN , 15 (9) , 2276-88.
  • Okunade, G. W., Miller, M. L., Pyne, G. J., Sutliff, R. L., O'Connor, K. T., Neumann, J. C., Andringa, A., Miller, D. A., Prasad, V., Doetschman, T., Paul, R. J., & Shull, G. E. (2004). Targeted ablation of plasma membrane Ca2+-ATPase (PMCA) 1 and 4 indicates a major housekeeping function for PMCA1 and a critical role in hyperactivated sperm motility and male fertility for PMCA4. . The Journal of Biological Chemistry , 279 (32) , 33742-50.
  • Gawenis, L. R., Ledoussal, C., Judd, L. M., Prasad, V., Alper, S. L., Stuart-Tilley, A., Woo, A. L., Grisham, C., Sanford, L. P., Doetschman, T., Miller, M. L., & Shull, G. E. (2004). Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric. . The Journal of Biological Chemistry , 279 (29) , 30531-9.
  • Kintner, D. B., Su, G., Lenart, B., Ballard, A. J., Meyer, J. W., Ng, L. L., Shull, G. E., & Sun, D. (2004). Increased tolerance to oxygen and glucose deprivation in astrocytes from Na(+)/H(+) exchanger isoform 1 null mice. . American Journal of Physiology. Cell Physiology , 287 (1) , C12-21.
  • Bachmann, O., Riederer, B., Rossmann, H., Groos, S., Schultheis, P. J., Shull, G. E., Gregor, M., Manns, M. P., & Seidler, U. (2004). The Na+/H+ exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 287 (1) , G125-33.
  • Clarke, L. L., Gawenis, L. R., Bradford, E. M., Judd, L. M., Boyle, K. T., Simpson, J. E., Shull, G. E., Tanabe, H., Ouellette, A. J., Franklin, C. L., & Walker, N. M. (2004). Abnormal Paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 286 (6) , G1050-8.
  • Chen, J., McLean, P. A., Neel, B. G., Okunade, G., Shull, G. E., & Wortis, H. H. (2004). CD22 attenuates calcium signaling by potentiating plasma membrane calcium-ATPase activity. . Nature Immunology , 5 (6) , 651-7.
  • Schultz, J. E. J., Glascock, B. J., Witt, S. A., Nieman, M. L., Nattamai, K. J., Liu, L. H., Lorenz, J. N., Shull, G. E., Kimball, T. R., & Periasamy, M. (2004). Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity. . American Journal of Physiology. Heart and Circulatory Physiology , 286 (3) , H1146-53.
  • Xu, J., Barone, S., Petrovic, S., Wang, Z., Seidler, U., Riederer, B., Ramaswamy, K., Dudeja, P. K., Shull, G. E., & Soleimani, M. (2003). Identification of an apical Cl-/HCO3- exchanger in gastric surface mucous and duodenal villus cells. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 285 (6) , G1225-34.
  • Amlal, H., Ledoussal, C., Sheriff, S., Shull, G. E., & Soleimani, M. (2003). Downregulation of renal AQP2 water channel and NKCC2 in mice lacking the apical Na+-H+ exchanger NHE3. . The Journal of Physiology , 553 (Pt 2) , 511-22.
  • Wang, Y., Meyer, J. W., Ashraf, M., & Shull, G. E. (2003). Mice with a null mutation in the NHE1 Na+-H+ exchanger are resistant to cardiac ischemia-reperfusion injury. . Circulation Research , 93 (8) , 776-82.
  • Woo, A. L., Noonan, W. T., Schultheis, P. J., Neumann, J. C., Manning, P. A., Lorenz, J. N., & Shull, G. E. (2003). Renal function in NHE3-deficient mice with transgenic rescue of small intestinal absorptive defect. . American Journal of Physiology. Renal Physiology , 284 (6) , F1190-8.
  • Shull, G. E., Okunade, G., Liu, L. H., Kozel, P., Periasamy, M., Lorenz, J. N., & Prasad, V. (2003). Physiological functions of plasma membrane and intracellular Ca2+ pumps revealed by analysis of null mutants. . Annals of the New York Academy of Sciences , 986 , 453-60.
  • Woo, A. L., Gildea, L. A., Tack, L. M., Miller, M. L., Spicer, Z., Millhorn, D. E., Finkelman, F. D., Hassett, D. J., & Shull, G. E. (2002). In vivo evidence for interferon-gamma-mediated homeostatic mechanisms in small intestine of the NHE3 Na+/H+ exchanger knockout model of congenital diarrhea. . The Journal of Biological Chemistry , 277 (50) , 49036-46.
  • Petrovic, S., Wang, Z., Ma, L., Seidler, U., Forte, J. G., Shull, G. E., & Soleimani, M. (2002). Colocalization of the apical Cl-/HCO3- exchanger PAT1 and gastric H-K-ATPase in stomach parietal cells. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 283 (5) , G1207-16.
  • Meyer, J. W., Flagella, M., Sutliff, R. L., Lorenz, J. N., Nieman, M. L., Weber, C. S., Paul, R. J., & Shull, G. E. (2002). Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na(+)-K(+)-2Cl(-) cotransporter. . American Journal of Physiology. Heart and Circulatory Physiology , 283 (5) , H1846-55.
  • Arredouani, A., Guiot, Y., Jonas, J., Liu, L. H., Nenquin, M., Pertusa, J. A., Rahier, J., Rolland, J., Shull, G. E., Stevens, M., Wuytack, F., Henquin, J., & Gilon, P. (2002). SERCA3 ablation does not impair insulin secretion but suggests distinct roles of different sarcoendoplasmic reticulum Ca(2+) pumps for Ca(2+) homeostasis in pancreatic beta-cells. . Diabetes , 51 (11) , 3245-53.
  • Lu, M., Wang, T., Yan, Q., Yang, X., Dong, K., Knepper, M. A., Wang, W., Giebisch, G., Shull, G. E., & Hebert, S. C. (2002). Absence of small conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter's) knockout mice. . The Journal of Biological Chemistry , 277 (40) , 37881-7.
  • Lorenz, J. N., Baird, N. R., Judd, L. M., Noonan, W. T., Andringa, A., Doetschman, T., Manning, P. A., Liu, L. H., Miller, M. L., & Shull, G. E. (2002). Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome. . The Journal of Biological Chemistry , 277 (40) , 37871-80.
  • Miller, M. L., Judd, L. M., Van Driel, I. R., Andringa, A., Flagella, M., Bell, S. M., Schultheis, P. J., Spicer, Z., & Shull, G. E. (2002). The unique ultrastructure of secretory membranes in gastric parietal cells depends upon the presence of H+, K+ -ATPase. . Cell and Tissue Research , 309 (3) , 369-80.
  • Walker, N. M., Flagella, M., Gawenis, L. R., Shull, G. E., & Clarke, L. L. (2002). An alternate pathway of cAMP-stimulated Cl secretion across the NKCC1-null murine duodenum. . Gastroenterology , 123 (2) , 531-41.
  • Nehrke, K., Arreola, J., Nguyen, H., Pilato, J., Richardson, L., Okunade, G., Baggs, R., Shull, G. E., & Melvin, J. E. (2002). Loss of hyperpolarization-activated Cl(-) current in salivary acinar cells from Clcn2 knockout mice. . The Journal of Biological Chemistry , 277 (26) , 23604-11.
  • Shillingford, J. M., Miyoshi, K., Flagella, M., Shull, G. E., & Hennighausen, L. (2002). Mouse mammary epithelial cells express the Na-K-Cl cotransporter, NKCC1: characterization, localization, and involvement in ductal development and morphogenesis. . Molecular Endocrinology (Baltimore, Md.) , 16 (6) , 1309-21.
  • Su, G., Kintner, D. B., Flagella, M., Shull, G. E., & Sun, D. (2002). Astrocytes from Na(+)-K(+)-Cl(-) cotransporter-null mice exhibit absence of swelling and decrease in EAA release. . American Journal of Physiology. Cell Physiology , 282 (5) , C1147-60.
  • Gawenis, L. R., Stien, X., Shull, G. E., Schultheis, P. J., Woo, A. L., Walker, N. M., & Clarke, L. L. (2002). Intestinal NaCl transport in NHE2 and NHE3 knockout mice. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 282 (5) , G776-84.
  • Kozel, P. J., Davis, R. R., Krieg, E. F., Shull, G. E., & Erway, L. C. (2002). Deficiency in plasma membrane calcium ATPase isoform 2 increases susceptibility to noise-induced hearing loss in mice. . Hearing Research , 164 (1-2) , 231-9.
  • Petrovic, S., Spicer, Z., Greeley, T., Shull, G. E., & Soleimani, M. (2002). Novel Schering and ouabain-insensitive potassium-dependent proton secretion in the mouse cortical collecting duct. . American Journal of Physiology. Renal Physiology , 282 (1) , F133-43.
  • Paul, R. J., Shull, G. E., & Kranias, E. G. (2002). The sarcoplasmic reticulum and smooth muscle function: evidence from transgenic mice. . Novartis Foundation Symposium , 246 , 228-38; discussion 2.
  • Ledoussal, C., Woo, A. L., Miller, M. L., & Shull, G. E. (2001). Loss of the NHE2 Na(+)/H(+) exchanger has no apparent effect on diarrheal state of NHE3-deficient mice. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 281 (6) , G1385-96.
  • Spicer, Z., Clarke, L. L., Gawenis, L. R., & Shull, G. E. (2001). Colonic H(+)-K(+)-ATPase in K(+) conservation and electrogenic Na(+) absorption during Na(+) restriction. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 281 (6) , G1369-77.
  • Ledoussal, C., Lorenz, J. N., Nieman, M. L., Soleimani, M., Schultheis, P. J., & Shull, G. E. (2001). Renal salt wasting in mice lacking NHE3 Na+/H+ exchanger but not in mice lacking NHE2. . American Journal of Physiology. Renal Physiology , 281 (4) , F718-27.
  • Wang, T., Yang, C. L., Abbiati, T., Shull, G. E., Giebisch, G., & Aronson, P. S. (2001). Essential role of NHE3 in facilitating formate-dependent NaCl absorption in the proximal tubule. . American Journal of Physiology. Renal Physiology , 281 (2) , F288-92.
  • Rossmann, H., Bachmann, O., Wang, Z., Shull, G. E., Obermaier, B., Stuart-Tilley, A., Alper, S. L., & Seidler, U. (2001). Differential expression and regulation of AE2 anion exchanger subtypes in rabbit parietal and mucous cells. . The Journal of Physiology , 534 (Pt 3) , 837-48.
  • Liu, L. H., Boivin, G. P., Prasad, V., Periasamy, M., & Shull, G. E. (2001). Squamous cell tumors in mice heterozygous for a null allele of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 Ca2+ pump. . The Journal of Biological Chemistry , 276 (29) , 26737-40.
  • Park, K., Evans, R. L., Watson, G. E., Nehrke, K., Richardson, L., Bell, S. M., Schultheis, P. J., Hand, A. R., Shull, G. E., & Melvin, J. E. (2001). Defective fluid secretion and NaCl absorption in the parotid glands of Na+/H+ exchanger-deficient mice. . The Journal of Biological Chemistry , 276 (29) , 27042-50.
  • Zhao, X. S., Shin, D. M., Liu, L. H., Shull, G. E., & Muallem, S. (2001). Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2(+/-) mice. . The EMBO Journal , 20 (11) , 2680-9.
  • Mennone, A., Biemesderfer, D., Negoianu, D., Yang, C. L., Abbiati, T., Schultheis, P. J., Shull, G. E., Aronson, P. S., & Boyer, J. L. (2001). Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 280 (2) , G247-54.
  • Brooks, H. L., Sorensen, A. M., Terris, J., Schultheis, P. J., Lorenz, J. N., Shull, G. E., & Knepper, M. A. (2001). Profiling of renal tubule Na+ transporter abundances in NHE3 and NCC null mice using targeted proteomics. . The Journal of Physiology , 530 (Pt 3) , 359-66.
  • Melvin, J. E., Nguyen, H. V., Evans, R. L., & Shull, G. E. (2000). What can transgenic and gene-targeted mouse models teach us about salivary gland physiology? . Advances in Dental Research , 14 , 5-11.
  • Ji, Y., Lalli, M. J., Babu, G. J., Xu, Y., Kirkpatrick, D. L., Liu, L. H., Chiamvimonvat, N., Walsh, R. A., Shull, G. E., & Periasamy, M. (2000). Disruption of a single copy of the SERCA2 gene results in altered Ca2+ homeostasis and cardiomyocyte function. . The Journal of Biological Chemistry , 275 (48) , 38073-80.
  • Boivin, G. P., Schultheis, P. J., Shull, G. E., & Stemmermann, G. N. (2000). Variant form of diffuse corporal gastritis in NHE2 knockout mice. . Comparative Medicine , 50 (5) , 511-5.
  • Shull, G E (2000). Gene knockout studies of Ca2+-transporting ATPases. . European Journal of Biochemistry / FEBS , 267 (17) , 5284-90.
  • Evans, R. L., Park, K., Turner, R. J., Watson, G. E., Nguyen, H. V., Dennett, M. R., Hand, A. R., Flagella, M., Shull, G. E., & Melvin, J. E. (2000). Severe impairment of salivation in Na+/K+/2Cl- cotransporter (NKCC1)-deficient mice. . The Journal of Biological Chemistry , 275 (35) , 26720-6.
  • Spicer, Z., Miller, M. L., Andringa, A., Riddle, T. M., Duffy, J. J., Doetschman, T., & Shull, G. E. (2000). Stomachs of mice lacking the gastric H,K-ATPase alpha -subunit have achlorhydria, abnormal parietal cells, and ciliated metaplasia. . The Journal of Biological Chemistry , 275 (28) , 21555-65.
  • Wheat, V. J., Shumaker, H., Burnham, C., Shull, G. E., Yankaskas, J. R., & Soleimani, M. (2000). CFTR induces the expression of DRA along with Cl(-)/HCO(3)(-) exchange activity in tracheal epithelial cells. . American Journal of Physiology. Cell Physiology , 279 (1) , C62-71.
  • Lee, M. G., Ahn, W., Choi, J. Y., Luo, X., Seo, J. T., Schultheis, P. J., Shull, G. E., Kim, K. H., & Muallem, S. (2000). Na(+)-dependent transporters mediate HCO(3)(-) salvage across the luminal membrane of the main pancreatic duct. . The Journal of Clinical Investigation , 105 (11) , 1651-8.
  • Choi, J. Y., Shah, M., Lee, M. G., Schultheis, P. J., Shull, G. E., Muallem, S., & Baum, M. (2000). Novel amiloride-sensitive sodium-dependent proton secretion in the mouse proximal convoluted tubule. . The Journal of Clinical Investigation , 105 (8) , 1141-6.
  • Szabó, E. Z., Numata, M., Shull, G. E., & Orlowski, J. (2000). Kinetic and pharmacological properties of human brain Na(+)/H(+) exchanger isoform 5 stably expressed in Chinese hamster ovary cells. . The Journal of Biological Chemistry , 275 (9) , 6302-7.
  • Nguyen, H. V., Shull, G. E., & Melvin, J. E. (2000). Muscarinic receptor-induced acidification in sublingual mucous acinar cells: loss of pH recovery in Na+-H+ exchanger-1 deficient mice. . The Journal of Physiology , 523 Pt 1 , 139-46.
  • Shull, G. E., Miller, M. L., & Schultheis, P. J. (2000). Lessons from genetically engineered animal models VIII. Absorption and secretion of ions in the gastrointestinal tract. . American Journal of Physiology. Gastrointestinal and Liver Physiology , 278 (2) , G185-90.
  • Evans, R. L., Bell, S. M., Schultheis, P. J., Shull, G. E., & Melvin, J. E. (1999). Targeted disruption of the Nhe1 gene prevents muscarinic agonist-induced up-regulation of Na(+)/H(+) exchange in mouse parotid acinar cells. . The Journal of Biological Chemistry , 274 (41) , 29025-30.
  • Flagella, M., Clarke, L. L., Miller, M. L., Erway, L. C., Giannella, R. A., Andringa, A., Gawenis, L. R., Kramer, J., Duffy, J. J., Doetschman, T., Lorenz, J. N., Yamoah, E. N., Cardell, E. L., & Shull, G. E. (1999). Mice lacking the basolateral Na-K-2Cl cotransporter have impaired epithelial chloride secretion and are profoundly deaf. . The Journal of Biological Chemistry , 274 (38) , 26946-55.
  • Lorenz, J. N., Schultheis, P. J., Traynor, T., Shull, G. E., & Schnermann, J. (1999). Micropuncture analysis of single-nephron function in NHE3-deficient mice. . The American Journal of Physiology , 277 (3 Pt 2) , F447-53.
  • Melvin, J. E., Park, K., Richardson, L., Schultheis, P. J., & Shull, G. E. (1999). Mouse down-regulated in adenoma (DRA) is an intestinal Cl(-)/HCO(3)(-) exchanger and is up-regulated in colon of mice lacking the NHE3 Na(+)/H(+) exchanger. . The Journal of Biological Chemistry , 274 (32) , 22855-61.
  • Wang, T., Yang, C. L., Abbiati, T., Schultheis, P. J., Shull, G. E., Giebisch, G., & Aronson, P. S. (1999). Mechanism of proximal tubule bicarbonate absorption in NHE3 null mice. . The American Journal of Physiology , 277 (2 Pt 2) , F298-302.
  • Kao, J., Fortner, C. N., Liu, L. H., Shull, G. E., & Paul, R. J. (1999). Ablation of the SERCA3 gene alters epithelium-dependent relaxation in mouse tracheal smooth muscle. . The American Journal of Physiology , 277 (2 Pt 1) , L264-70.
  • Nakamura, S., Amlal, H., Schultheis, P. J., Galla, J. H., Shull, G. E., & Soleimani, M. (1999). HCO-3 reabsorption in renal collecting duct of NHE-3-deficient mouse: a compensatory response. . The American Journal of Physiology , 276 (6 Pt 2) , F914-21.
  • Bell, S. M., Schreiner, C. M., Schultheis, P. J., Miller, M. L., Evans, R. L., Vorhees, C. V., Shull, G. E., & Scott, W. J. (1999). Targeted disruption of the murine Nhe1 locus induces ataxia, growth retardation, and seizures. . The American Journal of Physiology , 276 (4 Pt 1) , C788-95.
  • Baird, N. R., Orlowski, J., Szabó, E. Z., Zaun, H. C., Schultheis, P. J., Menon, A. G., & Shull, G. E. (1999). Molecular cloning, genomic organization, and functional expression of Na+/H+ exchanger isoform 5 (NHE5) from human brain. . The Journal of Biological Chemistry , 274 (7) , 4377-82.
  • Periasamy, M., Reed, T. D., Liu, L. H., Ji, Y., Loukianov, E., Paul, R. J., Nieman, M. L., Riddle, T., Duffy, J. J., Doetschman, T., Lorenz, J. N., & Shull, G. E. (1999). Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) gene. . The Journal of Biological Chemistry , 274 (4) , 2556-62.
  • Lee, M. G., Schultheis, P. J., Yan, M., Shull, G. E., Bookstein, C., Chang, E., Tse, M., Donowitz, M., Park, K., & Muallem, S. (1998). Membrane-limited expression and regulation of Na+-H+ exchanger isoforms by P2 receptors in the rat submandibular gland duct. . The Journal of Physiology , 513 ( Pt 2) , 341-57.
  • Schultheis, P. J., Lorenz, J. N., Meneton, P., Nieman, M. L., Riddle, T. M., Flagella, M., Duffy, J. J., Doetschman, T., Miller, M. L., & Shull, G. E. (1998). Phenotype resembling Gitelman's syndrome in mice lacking the apical Na+-Cl- cotransporter of the distal convoluted tubule. . The Journal of Biological Chemistry , 273 (44) , 29150-5.
  • Kozel, P. J., Friedman, R. A., Erway, L. C., Yamoah, E. N., Liu, L. H., Riddle, T., Duffy, J. J., Doetschman, T., Miller, M. L., Cardell, E. L., & Shull, G. E. (1998). Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. . The Journal of Biological Chemistry , 273 (30) , 18693-6.
  • Schultheis, P. J., Clarke, L. L., Meneton, P., Miller, M. L., Soleimani, M., Gawenis, L. R., Riddle, T. M., Duffy, J. J., Doetschman, T., Wang, T., Giebisch, G., Aronson, P. S., Lorenz, J. N., & Shull, G. E. (1998). Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger. . Nature Genetics , 19 (3) , 282-5.
  • Burnham, C. E., Flagella, M., Wang, Z., Amlal, H., Shull, G. E., & Soleimani, M. (1998). Cloning, renal distribution, and regulation of the rat Na+-HCO3- cotransporter. . The American Journal of Physiology , 274 (6 Pt 2) , F1119-26.
  • Wang, Z., Rabb, H., Haq, M., Shull, G. E., & Soleimani, M. (1998). A possible molecular basis of natriuresis during ischemic-reperfusion injury in the kidney. . Journal of the American Society of Nephrology : JASN , 9 (4) , 605-13.
  • Schultheis, P. J., Clarke, L. L., Meneton, P., Harline, M., Boivin, G. P., Stemmermann, G., Duffy, J. J., Doetschman, T., Miller, M. L., & Shull, G. E. (1998). Targeted disruption of the murine Na+/H+ exchanger isoform 2 gene causes reduced viability of gastric parietal cells and loss of net acid secretion. . The Journal of Clinical Investigation , 101 (6) , 1243-53.
  • Meneton, P., Schultheis, P. J., Greeb, J., Nieman, M. L., Liu, L. H., Clarke, L. L., Duffy, J. J., Doetschman, T., Lorenz, J. N., & Shull, G. E. (1998). Increased sensitivity to K+ deprivation in colonic H,K-ATPase-deficient mice. . The Journal of Clinical Investigation , 101 (3) , 536-42.
  • Liu, L. H., Paul, R. J., Sutliff, R. L., Miller, M. L., Lorenz, J. N., Pun, R. Y., Duffy, J. J., Doetschman, T., Kimura, Y., MacLennan, D. H., Hoying, J. B., & Shull, G. E. (1997). Defective endothelium-dependent relaxation of vascular smooth muscle and endothelial cell Ca2+ signaling in mice lacking sarco(endo)plasmic reticulum Ca2+-ATPase isoform 3. . The Journal of Biological Chemistry , 272 (48) , 30538-45.
  • Beitner-Johnson, D., Shull, G. E., Dedman, J. R., & Millhorn, D. E. (1997). Regulation of gene expression by hypoxia: a molecular approach. . Respiration Physiology , 110 (2-3) , 87-97.
  • Burnham, C. E., Amlal, H., Wang, Z., Shull, G. E., & Soleimani, M. (1997). Cloning and functional expression of a human kidney Na+:HCO3- cotransporter. . The Journal of Biological Chemistry , 272 (31) , 19111-4.
  • Wang, Z., Rabb, H., Craig, T., Burnham, C., Shull, G. E., & Soleimani, M. (1997). Ischemic-reperfusion injury in the kidney: overexpression of colonic H+-K+-ATPase and suppression of NHE-3. . Kidney International , 51 (4) , 1106-15.
  • Pathak, B. G., Shaughnessy, J. D., Meneton, P., Greeb, J., Shull, G. E., Jenkins, N. A., & Copeland, N. G. (1996). Mouse chromosomal location of three epithelial sodium channel subunit genes and an apical sodium chloride cotransporter gene. . Genomics , 33 (1) , 124-7.
  • Wang, Z., Schultheis, P. J., & Shull, G. E. (1996). Three N-terminal variants of the AE2 Cl-/HCO3- exchanger are encoded by mRNAs transcribed from alternative promoters. . The Journal of Biological Chemistry , 271 (13) , 7835-43.
  • Cougnon, M., Planelles, G., Crowson, M. S., Shull, G. E., Rossier, B. C., & Jaisser, F. (1996). The rat distal colon P-ATPase alpha subunit encodes a ouabain-sensitive H+, K+-ATPase. . The Journal of Biological Chemistry , 271 (13) , 7277-80.
  • Pathak, B. G., Shull, G. E., Jenkins, N. A., & Copeland, N. G. (1996). Mouse chromosomal location of four Na/H exchanger isoform genes. . Genomics , 31 (2) , 261-3.
  • Burk, S. E., Menon, A. G., & Shull, G. E. (1995). Analysis of the 5' end of the rat plasma membrane Ca(2+)-ATPase isoform 3 gene and identification of extensive trinucleotide repeat sequences in the 5' untranslated region. . Biochimica Et Biophysica Acta , 1240 (2) , 119-24.
  • Linn, S. C., Askew, G. R., Menon, A. G., & Shull, G. E. (1995). Conservation of an AE3 Cl-/HCO3- exchanger cardiac-specific exon and promoter region and AE3 mRNA expression patterns in murine and human hearts. . Circulation Research , 76 (4) , 584-91.
  • Keeton, T. P., & Shull, G. E. (1995). Primary structure of rat plasma membrane Ca(2+)-ATPase isoform 4 and analysis of alternative splicing patterns at splice site A. . The Biochemical Journal , 306 ( Pt 3) , 779-85.
  • Su, Y. R., Klanke, C. A., Houseal, T. W., Linn, S. C., Burk, S. E., Varvil, T. S., Otterud, B. E., Shull, G. E., Leppert, M. F., & Menon, A. G. (1994). Molecular cloning and physical and genetic mapping of the human anion exchanger isoform 3 (SLC2C) gene to chromosome 2q36. . Genomics , 22 (3) , 605-9.
  • Yu, F. H., Shull, G. E., & Orlowski, J. (1993). Functional properties of the rat Na/H exchanger NHE-2 isoform expressed in Na/H exchanger-deficient Chinese hamster ovary cells. . The Journal of Biological Chemistry , 268 (34) , 25536-41.
  • Wang, Z., Orlowski, J., & Shull, G. E. (1993). Primary structure and functional expression of a novel gastrointestinal isoform of the rat Na/H exchanger. . The Journal of Biological Chemistry , 268 (16) , 11925-8.
  • Kudrycki, K. E., & Shull, G. E. (1993). Rat kidney band 3 Cl-/HCO3- exchanger mRNA is transcribed from an alternative promoter. . The American Journal of Physiology , 264 (3 Pt 2) , F540-7.
  • Keeton, T. P., Burk, S. E., & Shull, G. E. (1993). Alternative splicing of exons encoding the calmodulin-binding domains and C termini of plasma membrane Ca(2+)-ATPase isoforms 1, 2, 3, and 4. . The Journal of Biological Chemistry , 268 (4) , 2740-8.
  • Shull, G. E., Clarke, D. M., & Gunteski-Hamblin, A. M. (1992). cDNA cloning of possible mammalian homologs of the yeast secretory pathway Ca(2+)-transporting ATPase. . Annals of the New York Academy of Sciences , 671 , 70-80; discussion 81.
  • Burk, S. E., & Shull, G. E. (1992). Structure of the rat plasma membrane Ca(2+)-ATPase isoform 3 gene and characterization of alternative splicing and transcription products. Skeletal muscle-specific splicing results in a plasma membrane Ca(2+)-ATPase with a novel calmodulin-binding domain. . The Journal of Biological Chemistry , 267 (27) , 19683-90.
  • Gunteski-Hamblin, A. M., Clarke, D. M., & Shull, G. E. (1992). Molecular cloning and tissue distribution of alternatively spliced mRNAs encoding possible mammalian homologues of the yeast secretory pathway calcium pump. . Biochemistry , 31 (33) , 7600-8.
  • Lytton, J., Westlin, M., Burk, S. E., Shull, G. E., & MacLennan, D. H. (1992). Functional comparisons between isoforms of the sarcoplasmic or endoplasmic reticulum family of calcium pumps. . The Journal of Biological Chemistry , 267 (20) , 14483-9.
  • Crowson, M. S., & Shull, G. E. (1992). Isolation and characterization of a cDNA encoding the putative distal colon H+,K(+)-ATPase. Similarity of deduced amino acid sequence to gastric H+,K(+)-ATPase and Na+,K(+)-ATPase and mRNA expression in distal colon, kidney, and uterus. . The Journal of Biological Chemistry , 267 (19) , 13740-8.
  • Fiedler, M. A., Nemecz, Z. K., & Shull, G. E. (1992). Cloning and sequence analysis of rat cystic fibrosis transmembrane conductance regulator. . The American Journal of Physiology , 262 (6 Pt 1) , L779-84.
  • Orlowski, J., Kandasamy, R. A., & Shull, G. E. (1992). Molecular cloning of putative members of the Na/H exchanger gene family. cDNA cloning, deduced amino acid sequence, and mRNA tissue expression of the rat Na/H exchanger NHE-1 and two structurally related proteins. . The Journal of Biological Chemistry , 267 (13) , 9331-9.
  • Linn, S. C., Kudrycki, K. E., & Shull, G. E. (1992). The predicted translation product of a cardiac AE3 mRNA contains an N terminus distinct from that of the brain AE3 Cl-/HCO3- exchanger. Cloning of a cardiac AE3 cDNA, organization of the AE3 gene, and identification of an alternative transcription initiation site. . The Journal of Biological Chemistry , 267 (11) , 7927-35.
  • Newman, P. R., & Shull, G. E. (1991). Rat gastric H,K-ATPase beta-subunit gene: intron/exon organization, identification of multiple transcription initiation sites, and analysis of the 5'-flanking region. . Genomics , 11 (2) , 252-62.
  • Newman, P. R., Greeb, J., Keeton, T. P., Reyes, A. A., & Shull, G. E. (1990). Structure of the human gastric H,K-ATPase gene and comparison of the 5'-flanking sequences of the human and rat genes. . DNA and Cell Biology , 9 (10) , 749-62.
  • Shull, G E (1990). cDNA cloning of the beta-subunit of the rat gastric H,K-ATPase. . The Journal of Biological Chemistry , 265 (21) , 12123-6.
  • Kudrycki, K. E., Newman, P. R., & Shull, G. E. (1990). cDNA cloning and tissue distribution of mRNAs for two proteins that are related to the band 3 Cl-/HCO3- exchanger. . The Journal of Biological Chemistry , 265 (1) , 462-71.
  • Burk, S. E., Lytton, J., MacLennan, D. H., & Shull, G. E. (1989). cDNA cloning, functional expression, and mRNA tissue distribution of a third organellar Ca2+ pump. . The Journal of Biological Chemistry , 264 (31) , 18561-8.
  • Greeb, J., & Shull, G. E. (1989). Molecular cloning of a third isoform of the calmodulin-sensitive plasma membrane Ca2+-transporting ATPase that is expressed predominantly in brain and skeletal muscle. . The Journal of Biological Chemistry , 264 (31) , 18569-76.
  • Koch, W. J., Hui, A., Shull, G. E., Ellinor, P., & Schwartz, A. (1989). Characterization of cDNA clones encoding two putative isoforms of the alpha 1 subunit of the dihydropyridine-sensitive voltage-dependent calcium channel isolated from rat brain and rat aorta. . FEBS Letters , 250 (2) , 386-8.
  • Kudrycki, K. E., & Shull, G. E. (1989). Primary structure of the rat kidney band 3 anion exchange protein deduced from a cDNA. . The Journal of Biological Chemistry , 264 (14) , 8185-92.
  • Gunteski-Hamblin, A. M., Greeb, J., & Shull, G. E. (1988). A novel Ca2+ pump expressed in brain, kidney, and stomach is encoded by an alternative transcript of the slow-twitch muscle sarcoplasmic reticulum Ca-ATPase gene. Identification of cDNAs encoding Ca2+ and other cation-transporting ATPases using an oligonucleotide probe derived from the ATP-binding site. . The Journal of Biological Chemistry , 263 (29) , 15032-40.
  • Shull, G. E., & Greeb, J. (1988). Molecular cloning of two isoforms of the plasma membrane Ca2+-transporting ATPase from rat brain. Structural and functional domains exhibit similarity to Na+,K+- and other cation transport ATPases. . The Journal of Biological Chemistry , 263 (18) , 8646-57.
  • Dickey, L. F., Wang, Y. H., Shull, G. E., Wortman, I. A., & Theil, E. C. (1988). The importance of the 3'-untranslated region in the translational control of ferritin mRNA. . The Journal of Biological Chemistry , 263 (7) , 3071-4.
  • Shull, G. E., Young, R. M., Greeb, J., & Lingrel, J. B. (1988). Overview: amino acid sequences of the alpha and beta subunits of the Na,K-ATPase. . Progress in Clinical and Biological Research , 268A , 3-18.
  • Small, S. J., Shull, G. E., Santoni, M. J., & Akeson, R. (1987). Identification of a cDNA clone that contains the complete coding sequence for a 140-kD rat NCAM polypeptide. . The Journal of Cell Biology , 105 (5) , 2335-45.
  • Young, R. M., Shull, G. E., & Lingrel, J. B. (1987). Multiple mRNAs from rat kidney and brain encode a single Na+,K+-ATPase beta subunit protein. . The Journal of Biological Chemistry , 262 (10) , 4905-10.
  • Shull, G. E., & Lingrel, J. B. (1987). Isolation and characterization of a cDNA for the catalytic subunit of the (Na+ + K+)-ATPase. . Society of General Physiologists Series , 41 , 301-21.
  • Shull, G. E., & Lingrel, J. B. (1986). Molecular cloning of the rat stomach (H+ + K+)-ATPase. . The Journal of Biological Chemistry , 261 (36) , 16788-91.
  • Shull, G. E., Greeb, J., & Lingrel, J. B. (1986). Molecular cloning of three distinct forms of the Na+,K+-ATPase alpha-subunit from rat brain. . Biochemistry , 25 (25) , 8125-32.
  • Shull, G E (1984). Differential inhibition of protein synthesis: a possible biochemical mechanism of thalidomide teratogenesis. . Journal of Theoretical Biology , 110 (3) , 461-86.
  • Shull, G. E., & Theil, E. C. (1983). Regulation of ferritin mRNA: a possible gene-sparing phenomenon. Induction of ferritin synthesis by iron in liver as well as red cells combines high translational efficiency with increased utilization of preformed ferritin mRNA. . The Journal of Biological Chemistry , 258 (13) , 7921-3.
  • Shull, G. E., & Theil, E. C. (1982). Translational control of ferritin synthesis by iron in embryonic reticulocytes of the bullfrog. . The Journal of Biological Chemistry , 257 (23) , 14187-91.
  • Shull, G. E., Miller, M. L., & Prasad, V. Secretory pathway stress responses as possible mechanisms of disease involving Golgi Ca2+ pump dysfunction. . BioFactors (Oxford, England) , 37 (3) , 150-8.
  • Shull, G. E., Lane, L. K., & Lingrel, J. B. Amino-acid sequence of the beta-subunit of the (Na+ + K+)ATPase deduced from a cDNA. . Nature , 321 (6068) , 429-31.
  • Shull, G. E., Schwartz, A., & Lingrel, J. B. Amino-acid sequence of the catalytic subunit of the (Na+ + K+)ATPase deduced from a complementary DNA. . Nature , 316 (6030) , 691-5.

    Research Grants:

  • DK050594 NIDDK. Genetic Models for Disorders of Acid-Base TransportOur objective is to understand the functions and coupling modes of bicarbonate and proton transporters in transepithelial ion transport. HCO3 and H are generated from H2O and CO2 via carbonic anhydrase activity and coupled to transport of other ions by Na/H exchangers (NHE1-4), Cl/HCO3 exchangers (AE1-4, PAT1, DRA), Na- HCO3 cotransporters (NBCe1, NBCe2), H,K-ATPases, and others. In coupled systems, they mediate gastric acid secretion; maintain fluidity and pH of lumenal contents in intestine; recover ions and water in colon; and control acid-base, electrolyte, and fluid excretion by the kidney. To study these issues, we are utilizing mice with genetic ablation of various acid-base transporters. In Aim 1, the mechanisms of HCl secretion in stomach and maintenance of parietal cell (PC) viability will be analyzed by testing the hypotheses that AE2 is the major basolateral Cl/HCO3 exchanger that balances HCl secretion; that AE2 is coupled with the basolateral NHE4 Na/ H exchanger for volume loading; that NHE4 and NHE2 are required for PC viability; and that CLIC intracellular Cl channels are required for acid secretion. Aim 2 will test the hypotheses that reductions in apical NaCl absorption in the intestinal tract involving coupled Cl/HCO (PAT1, DRA) and Na/H (NHE3) exchange can correct perturbations of lumenal fluidity and pH in Cystic Fibrosis (CF) and lessen the severity of CF intestinal disease; and that basolateral AE2 in concert with apical NHE3 and/or colonic H,K-ATPase mediates Na-HCO3 and K-HCO3 absorption in the intestinal tract. Aim 3 will test the hypotheses that NBCe1 and the AE4 Cl/HCO3 exchanger, each a component of coupled systems in different segments of the kidney, contribute to Na-HCO3 absorption; that NBCe2 mediates a unique Na-HCO3 secretory function in the collecting duct; and that the colonic H,K-ATPase contributes to K-HCO3 absorption in the collecting duct. These studies will expand our understanding of the coupling modes that allow these transporters to mediate both absorptive and secretory functions. They have clinical relevance to gastroesophageal reflux and other diseases involving acid secretion; diarrheas; cystic fibrosis intestinal disease; and renal mechanisms for recovery from disorders of systemic acid-base, electrolyte, and fluid-volume homeostasis caused by gastrointestinal and other diseases. PUBLIC HEALTH RELEVANCE: The goal of this project is to understand the functions and interactions of proteins that transport acid (protons) and base (bicarbonate) across cell membranes in the gastrointestinal tract and kidney. To do this we are analyzing mouse models in which these proteins have been mutated. These studies will expand our understanding of the role of these transporters in absorptive and secretory functions, and have clinical relevance to gastroesophageal reflux disease; diarrheas; cystic fibrosis intestinal disease; and renal mechanisms for recovery from disorders of acid-base, electrolyte, and fluid-volume homeostasis caused by gastrointestinal and other diseases. The goal is to understand the functions and interactions of proteins that transport acid and base across cell membranes in the gastro-intestinal tract and kidney.To do this we are analyzing mouse models in which these proteins have been mutated. These studies will expand our understanding of the role of these transporters in absorptive and secretory functions, and have clinical relevance to gastroesophageal reflux disease; diarrheas; cystic fibrosis intestinal disease; and renal mechanisms for recovery from disorders of acid-base, electrolyte, and fluid-volume homeostasis caused by gastrointestinal and other diseases. - Grant, PI, Active.
  • R01-HL-61974 National Heart, Lung and Blood Institute. Mouse Models for Genetic Disorders of Calcium Transport, PI, Closed.
  • 5-R37-DK-50594-11-A0-S0-E0 National Inst of Diabetes and Digestive and Kidney Disease. Models for Genetic Disorders, PI, Closed.
  • 5-R01-DK-50594-04-A0-S0-E0 National Inst of Diabetes and Digestive and Kidney Disease. Models for Genetic Disorders of Acid-Base Transport, PI, Closed.
  • 5-R01-HL-61974-05-A0-S0-E0 National Heart, Lung and Blood Institute. Mouse Models for Genetic Disorders of Calcium Transport, PI, Closed.
  • R37 DK050594 National Inst of Diabetes and Digestive and Kidney Disease. Models for Genetic Disorders, PI, Closed.
  • R01 DK079979 National Inst of Diabetes and Digestive and Kidney Disease. Intestinal epithelial Ammonium Transport, Collaborator, Active.
  • 414843-G / R01 DE09692-17 National Institute of Dental and Craniofacial Research. Mechanisms of Anion Transport in Salivary Glands, PI, Closed.
  • 2 R01 HL061974-10A1 National Heart, Lung and Blood Institute. Mouse Models for Ion Homeostasis Defects in Heart, PI, Closed.
  • R01 DK050594 National Inst of Diabetes and Digestive and Kidney Disease. Genetic Models for Disorders of Acid-Base Transport, PI, Active.
  • R21 NS077022 National Institute of Neurological Disorders and Stroke. The Interaction Between ATP13A2 and Alpha-Synuclein in Mice, Collaborator, Active.