The primary aim of the proposed work is to develop microelectrodes for determining if nasal membrane cholesterol is elevated in human cystic fibrosis. Studies will calibrate the electrodes through solution experiments and validate this calibration using a new proposed influx titration assay where the electrode is used as an indicator of influx. Human studies using the electrodes will involve single cell studies on epithelial cells from nasal scrapes. In vivo electrode measurements in the human nose are also proposed. In developing the measurements as a diagnostic tool, implementation of in vitro measurements at cells and mouse tissues is proposed to establish the relationship between CFTR function and plasma membrane cholesterol content.

Public Health Relevance

Microelectrodes are used to measure cholesterol efflux from cells and tissues. In vivo experiments are proposed in the human nose to test the hypothesis that cholesterol efflux rate can be used as a diagnostic tool in the study of human cystic fibrosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB009481-04
Application #
8609027
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Korte, Brenda
Project Start
2011-04-01
Project End
2015-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
4
Fiscal Year
2014
Total Cost
$303,473
Indirect Cost
$100,973
Name
Case Western Reserve University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Rymut, Sharon M; Harker, Alyssa; Corey, Deborah A et al. (2013) Reduced microtubule acetylation in cystic fibrosis epithelial cells. Am J Physiol Lung Cell Mol Physiol 305:L419-31
Manson, Mary E; Corey, Deborah A; Bederman, Ilya et al. (2012) Regulatory role of ýý-arrestin-2 in cholesterol processing in cystic fibrosis epithelial cells. J Lipid Res 53:1268-76
Cianciola, Nicholas L; Carlin, Cathleen R; Kelley, Thomas J (2011) Molecular pathways for intracellular cholesterol accumulation: common pathogenic mechanisms in Niemann-Pick disease Type C and cystic fibrosis. Arch Biochem Biophys 515:54-63