LARA R. GAWENIS

Assistant Professor of Physiology
e-mail: lara.gawenis@hsc.utah.edu
 
Education  |  Research Interests  |  
Publications


Education

Bachelor of Science, 1995, University of Houston.

Ph.D. in Physiology, 2001, University of Missouri-Columbia.

Research Interests

The broad focus of our laboratory is investigation of the role of ion transport proteins in epithelial cell ion transport, differentiation, maturation, and apoptosis in health and disease, with a particular emphasis on 1) the roles of specific ion transporters in transepithelial absorption and secretion across intestinal and airway epithelia and 2) the roles of basolateral ion transporters in gastric epithelial cell physiology.  Studies in the laboratory involve measurements of ion transport activity using fluorescent dyes to monitor intracellular pH (pHi) by microfluorimetry or electrophysiological recordings, pH stat and isotopic flux studies in Ussing chambers of native mucosa and cell lines derived from transgenic and gene-targeted (“knockout”) mice.  Molecular studies in the laboratory involve the measurements of gene expression in the mice (Northern blots, microarrays, Western blots), cloning of specific murine transporters for functional expression studies in heterologous cell systems, and development of transgenic and gene-targeted ("knockout") mice.

Our laboratory is interested in the roles of ion transporters in the movement of acid, base, and electrolytes across epithelial tissues (airway, biliary and intestinal), which are of critical importance in homeostatic processes that are disturbed in a number of human disease states (e.g. cystic fibrosis and secretory diarrhea).  Regulation of electrolyte and water homeostasis relies on a balance between the activities of secretory and absorptive transporters which previous studies have shown to be coordinately regulation with respect to both expression and activity.  These studies utilize both knockout and transgenic mouse models to investigate the relative physiological roles of individual transporters, regulation of transport by cyclic nucleotides and intracellular calcium, and coordinating interactions among the transport processes.  In addition, the regulation of acid-base transporters is important for maintenance of pHi, a factor which is closely tied to the control of epithelial proliferation and apoptosis.

Research on gastric epithelial cell physiology has focused on the roles of basolateral ion transporters in gastric acid secretion as well as in the differentiation and function of other cell types in the gastric glandular epithelium, a process which requires the presence of mature, functional parietal cells.  The focus of this research area is to investigate the roles of specific basolateral membrane ion transport proteins in gastric physiology by examining coupling between transporters for cell volume expansion, the role of each transporter in gastric epithelial cell differentiation, and alterations in transporter expression/function during hypergastrinemia, inflammation and Helicobacter colonization.

Publications

Gawenis, L.R., Bradford, E.M., Pradad, V. and Shull,G.E. (in preparation) AE2 Cl-/HCO3- exchanger is required for normal cAMP-stimulated anion secretion across murine proximal colon.

Simpson, J.E., Schweinfest, C., Shull, G.E., Gawenis, L.R., Walker, N.M., Boyle, K.T., Soleimani, M., Clark, L.L. (submitted) PAT-1 (slc26a6) is the predominant apical membrane Cl-/HCO3- exchanger in the upper villous epithelium of murine duodenum.  A. J. Physiol.

Gawenis, L.R., Bradford, E.M., Lorenz, J.N., Simpson, J.E., Clark, L.L., Woo, A., Grisham, C., Sanford, L.P., Doetschmann, T., Miller, M.L. Shull, G.E. (submitted) Proximal renal tubular acidosis, intestinal obstructions, and colonic anion secretory defects in mice lacking the NBC1 Na+/HCO3- cotransporter.  J. Biol. Chem.

Simpson, J.E., Gawenis, L.R., Boyle, K.T., Walker, N.M. and Clark, L.L. (2005) Chloride conductance of CFTR facilitates basal Cl-/HCO3- exchange in the villous epithelium of intact murine duodenum.  Am. J. Physiol. 288: G1241-G1251

Gawenis, L.R., Greeb, J., Grisham, C., Sanford, L.P., Prasad, V.S., Doetschmann, T., Miller, M. and Shull, G.E. (2005) Impaired gastric acid secretion in NHE4 Na+/H+ exchanger knockout mice.  J. Biol. Chem. 280: 12781-12789.

Bailey, M.A., Giebisch, G., Abbiati, T., Aronson, P.S., Gawenis, L.R., Shull, G.E. and Wang, T. (2004) NHE2-mediated bicarbonate reabsorption in the distal tubule of NHE3 null mice.  J. Physiol. 561: 765-775.

Gawenis, L.R., Hut, H., Bot, A.G.M., Shull, G.E., de Jonge, H.R., Stien, X., Miller, M. and Clark, L.L. (2004) Electroneutral sodium absorption and electrogenic anion secretion across murine intestine are regulated in parallel.  Am. J. Physiol. 287: G1140-G1149.

Gawenis, L.R., Ledoussal, C., Judd, L.M., Alper, S., Stuart-Tilly, A., Grisham, C., Sanford, L.P., Woo, A., Prasad, V.S., Doetschmann, T., Miller, M.L. and Shull, G.E. (2004) Mice with targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric.  J. Biol. Chem. 279: 30531-30539.

Clark, L.L., Gawenis, L.R., Hwang, T.C., Walker, N.M., Gruis, D. and Price, E.M. (2004) A domain mimic corrects ΔF508 CFTR processing and restores anion secretion in cystic fibrosis epithelia.  Am. J. Physiol. 287: C192-C199, 2004.

Clark, L.L., Gawenis, L.R., Bradford, E.M., Judd, L.M., Boyle, K.T., Simpson, J.E., Shull, G.E., Ouellette, A.J., Franklin, C.L. and Walker, N.M. (2004) Abnormal Paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice.  Am. J. Physiol. 286: G1050-G1058.

Gawenis, L.R., Boyle, K.T., Palmer, B.A., Walker, N.M. and Clark, L.L. (2004) Lateral intercellular space volume as a determinant of CFTR-mediated anion secretion across small intestinal mucosa.  Am. J. Physiol. 286: G1015-G1023.

 
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