Biomedical Research Funded in 2003

1) Paul Quinton, PhD, University of San Diego, La Jolla, California, Principal Investigator and

Jeffery Wang, PhD, Post Doctoral Fellow

"The Potential Role of Small Airways in CF Lung Disease"

This study was conducted to investigate ion transport of bronchiolar epithelia of both animal

and human, especially 1) Cl (chlorine) transport through CFTR, 2) and Na (sodium) transport

through the Epithelial Na Channel (ENaC). Results showed that Na permeability through

tight junction suggested that the epithelium is capable of secretion. Human bronchioles

epithelium exhibit qualitatively similar ion transport properties similar to those found in pig

bronchioles. These findings suggest that distal bronchioles of the human lung exhibit

significant electrolyte transport activity and ion barrier properties that are heavily dependent

upon the function and activity of CFTR dependent Cl transport in the lung that probably

support both absorptive and secretory functions.

Amount Funded: $37,500.00

2) Reen Wu, PhD, University of Davis, Davis, California, Principal Investigator and

Yin Chen, PhD, Post Doctoral Fellow

"Characterization of the Novel Gel-Forming mucin Gene-MUC19 in Cystic Fibrosis"

This study is currently being conducted to determine if MUC19 is the major contributor to

the mucus over-production in CF. Two potential results are that MUC19 does not change

or that it decreases in CF. If there's no change, MUC19 is not the major contributor, and

the focus of study will be shifted to other gel-forming mucins, like MUC2 or MUC5B. However,

if MUC19 does decrease in CF, further studies will be conducted on the alteration of the

airway mucus structure.

Amount Funded: $37,500.00

3) Ron Kopito, PhD, Stanford University, Stanford, California, Principal Investigator and

Kwon-Yul Ryu, PhD, Post Doctoral Fellow

"Small Molecule Screening Approach to Search for Suppressors of Delta 508 Misfolding"

The purpose of this project is to identify small molecules capable of enhancing the folding

and/or stability of misfolded Delta F508. So far, researchers have found that the presence of

an internal S-tag in the 4th extracellular loop of CFTR may interfere with the folding and/or

trafficking of CFTR. S-tag insertions should be both detectable and non-perturbing.

Because the current S-tag insertion perturbs CFTR, alternate approaches are being taken.

One approach is inserting the minimal S-peptide (15 amino acids) into the 4th extracellular

loop, although a possible drawback is the disruption of the trafficking of the wildtype and/or

mutant protein.

Amount Funded: $37,500.00

4) Marybeth Howard, PhD, University of California San Francisco, San Francisco, California, Principal Investigator and

Jeremie Roux, Fellow

"Regulation of Wild Type and Delta F508 CFTR Protein Maturation and Stability"- Extension

Amount Funded: $20,000.00

5) Terry Machen, PhD, University of California Berkeley, Berkeley, California, Principal Investigator and

Christian Schwarzer, PhD, Post Doctoral Fellow

"Redox Regulation in CF Airway Epithelia"- Extension

Amount Funded: $20,000.00