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Lane L. Clarke, DVM, PhD

Professor, Department of Biomedical Sciences
 Office Location: 324D Dalton Cardiovascular Research Center
Office Phone: 573-882-7049

Laboratory Location: 220 Dalton Cardiovascular Research Center
Laboratory Phone: 573-882-2847
ClarkeL@missouri.edu

Research Interests

Cystic fibrosis and epithelial transport of ions and nutrients

Research Description

Salt and water homeostasis is dependent on the processes of electrolyte and acid-base transport across epithelial tissues. Clarke's research interests involve the investigation of ion transport across epithelial tissues (airway, reproductive and intestinal) during health and disease. The major focus is to understand the role of the cystic fibrosis transmembrane conductance regulator protein (CFTR) in the regulation of acid-base transport across alimentary epithelia. CFTR is the protein product of the gene that is mutated in cystic fibrosis (CF) and normally functions in epithelial cells as a cyclic AMP-regulated anion channel. Present studies investigate the role of CFTR in promoting bicarbonate transport and inhibiting sodium absorption during cAMP stimulation of the intestinal epithelium. Most experiments involve electrophysiological recordings of epithelial tissue from mice with gene-targeted deletion ("knockout") of CFTR and/or other specific acid-base transporting proteins, including Na+/H+- or H+/K+ ATPase exchange proteins.

Collaborative projects in the laboratory include investigations of:

  • Correction of defective protein processing of Delta F508 CFTR by expression of subdomains of CFTR in Delta F508 cell line;
  • Defective electrolyte and fluid transport across the efferent ductules of estrogen-receptor (ER) knockout mice. Studies of the ER knockout mice have revealed a role of estrogen in the male reproductive tract;
  • Purinoceptor regulation of salt and water secretion. Purinoceptors that bind extracellular nucleotides regulate the function of an anion channel that bypasses the defective channel in cystic fibrosis disease; and
  • Intestinal calcium and phosphorus absorption in the cystic fibrosis mouse. Both teeth and bone mineralization are abnormal in the CF mice.

Techniques used in the laboratory for these various projects include cell culture, quantitative RT-PCR, retroviral gene transfection of epithelial cells, pH stat and isotopic flux studies with Ussing chambers, intracellular microelectrode analysis and microfluoroscopy.

Professional Background

  • Obtained PhD from North Carolina State University.
  • Obtained DVM from University of Missouri.

Selected Publications

  • Clarke LL, Grubb BR, Gabriel SE, Smithies O, Koller BH, and Boucher RC. Defective epithelial chloride transport in a gene-targeted mouse model of cystic fibrosis. Science, 257:1125-1128. 1992.
  • Clarke LL, Grubb BR, Yankaskas JR, Cotton CU, McKenzie A, and Boucher RC. Relationship of a non-CFTR-mediated chloride conductance to organ-level disease in cftr (-/-) mice. Proc. Natl. Acad. Sci. 91(2):479-483, 1994.
  • Gawenis, LR, Franklin, CL, Simpson, JE, Palmer, BA, Walker, NM, Wiggins, TM and Clarke, LL. cAMP inhibition of murine intestinal Na+/H+ exchange requires CFTR-mediated cell shrinkage of villus epithelium. Gastroenterology 125: 1124-1148, 2003.
  • Gawenis, LR, Boyle, KT, Palmer, BA, Walker, NM, and Clarke, LL. Lateral intercellular space volume as a determinant of CFTR-mediated anion secretion across small intestinal mucosa. Am. J. Physiol. 286: G1015-G1023, 2004.
  • Clarke, LL, Gawenis, LR, Hwang, T-C, Gruis, DB and Price, EM. A domain mimic increases DF508 CFTR trafficking and restores cAMP-stimulated anion secretion in cystic fibrosis epithelia. Am. J. Physiol. 287: C192-C199, 2004.
  • Gawenis, LR, Hut, H, Bot, AGM, Shull, GE, De Jonge, HR, Stein, X, Miller, ML and Clarke, LL. Electroneutral sodium absorption and electrogenic anion secretion across murine small intestine are regulated in parallel. Am. J. Physiol. 287: G1140-G1149, 2004.

Published by Dalton Cardiovascular Research Center, 134 Research Park Dr., Columbia, MO 65211
Phone: 573-882-7588 | Fax: 573-884-4232 | Email: dalton@missouri.edu
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